A Phase 1/2 interventional study of pralsetinib (BLU-667) in RET-altered Non Small Cell Lung Cancer, Medullary Thyroid Cancer and RET-altered Papillary Thyroid Cancer, sponsored by Hoffmann-La Roche. Completed at 71 sites in 13 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-31.
Sponsored by Hoffmann-La Roche · Phase 1/2, Interventional, and Treatment
This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of pralsetinib (BLU-667) administered orally in participants with medullary thyroid cancer (MTC), RET-altered NSCLC and other RET-altered solid tumors.
The study consists of 2 parts, a dose-escalation part (Phase 1) and an expansion part (Phase 2). Both parts will enroll participants with advanced non-resectable NSCLC, advanced non-resectable thyroid cancer and other advanced solid tumors that have progressed following standard systemic therapy, have not adequately responded to standard systemic therapy, or the participants must be intolerant to or the Investigator has determined that treatment with standard therapy is not appropriate, or there must be no accepted standard therapy for their disease.
144 studies on the registry are indexed under Carcinoma, Medullary; 30 are open to participants now.
This study's enrollment of 590 is above the median of 30 across 100 interventional studies indexed under Carcinoma, Medullary.
Browse Carcinoma, Medullary studies →Hoffmann-La Roche is the lead sponsor of 2,101 studies on the registry; 87 are open to participants now.
Of its 330 completed or terminated interventional studies of FDA-regulated products, 248 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Diagnosis during dose escalation (Phase 1) - documented, definitively diagnosed non-resectable advanced solid tumor.
Diagnosis during dose expansion (Phase 2) - All participants (with the exception of participants with MTC enrolled in Groups 3, 4, and 9) must have an oncogenic RET-rearrangement/fusion or mutation (excluding synonymous, frameshift, and nonsense mutations) solid tumor, as determined by local or central testing of tumor or circulating tumor nucleic acid in blood; as detailed below.
Key Exclusion Criteria:
Participants had any of the following within 14 days prior to the first dose of study drug:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Multiple doses of pralsetinib (BLU-667) for oral administration.
Drug: pralsetinib (BLU-667)
Oral dose of pralsetinib (BLU-667) as determined during Dose Escalation.
Drug: pralsetinib (BLU-667)
pralsetinib (BLU-667) is a potent and selective inhibitor of the RET mutations, fusions, and predicted resistant mutants
Also known as: BLU-667
Phase 1 : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib
MTD was defined as the highest tolerated dose of pralsetinib without causing dose limiting toxicities (DLTs). DLT was defined as any Grade ≥3 adverse event (AE) occurring during Cycle 1 during Phase 1 (dose escalation) that is not clearly caused by something other than pralsetinib. RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase.
Time frame: Up to approximately 30.8 months
Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs)
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Time frame: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years)
Phase 2: Overall Response Rate (ORR)
ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) for at least two assessments with at least 28 days apart and no disease progression (PD) in between. Per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). ORR and its two-sided 95% CI, based on the exact binomial distribution (Clopper-Pearson), were presented.
Time frame: Up to approximately 79.8 months
Phase 1: ORR
ORR was defined as the percentage of participants with a confirmed CR or PR for at least two assessments with at least 28 days apart and no PD in between. Per RECIST v1.1, CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). ORR and its two-sided 95% CI, based on the exact binomial distribution (Clopper-Pearson), was presented.
Time frame: Up to approximately 28 months
Phase 1 and Phase 2: ORR in RET-fusion Positive NSCLC Participants With Specific RET Gene Status
Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., Kinesin family member 5B (KIF5B), coiled-coil domain containing 6 (CCDC6), nuclear receptor coactivator 4 (NCOA4)). RET genotypes were determined by local testing and/or central analysis of circulating tumor deoxyribonucleic acid (ctDNA). ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.
Time frame: Up to approximately 79.8 months
Phase 1 and Phase 2: ORR in RET-mutation MTC Participants With Specific RET Gene Status
Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.
Time frame: Up to approximately 79.8 months
Phase 1 and Phase 2: ORR in RET-fusion Positive TC Participants With Specific RET Gene Status
Oncogenic RET activation has been implicated as a driver in both MTC and differentiated TC (DTC). These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.
Time frame: Up to approximately 79.8 months
Phase 1 and Phase 2: Clinical Benefit Rate (CBR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status
Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR, or stable disease (SD) which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
Time frame: Up to approximately 79.8 months
Phase 1 and Phase 2: CBR in RET-mutation MTC Participants With Specific RET Gene Status
Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR, or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
Time frame: Up to approximately 79.8 months
Phase 1 and Phase 2: CBR in RET-fusion Positive TC Participants With Specific RET Gene Status
Oncogenic RET activation has been implicated as a driver in both MTC and DTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
Time frame: Up to approximately 79.8 months
Phase 1 and Phase 2: Disease Control Rate (DCR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status
Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
Time frame: Up to approximately 79.8 months
Phase 1 and Phase 2: DCR in RET-mutation MTC Participants With Specific RET Gene Status
Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
Time frame: Up to approximately 79.8 months
Phase 1 and Phase 2: DCR in RET-fusion Positive TC Participants With Specific RET Gene Status
Oncogenic RET activation has been implicated as a driver in both MTC and DTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
Time frame: Up to approximately 79.8 months
Phase 1 and Phase 2: Duration of Response (DOR) in RET-mutation NSCLC Participants With Specific RET Gene Status
Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5), CCDC6, NCOA4). RET genotypes were determined by local testing \&/or central analysis of circulating tumor deoxyribonucleic acid (ctDNA). DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR=disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to \<10 mm. PR=at least a 30% decrease in SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study. DOR was analyzed using the Kaplan-Meier (KM) method.
Time frame: Up to approximately 79.8 months
Phase 1 and Phase 2: DOR in RET-mutation MTC Participants With Specific RET Gene Status
Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR= disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to \<10 mm. PR=at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study (including baseline). DOR was analyzed using the Kaplan-Meier (KM) method.
Time frame: Up to approximately 79.8 months
Phase 1 and Phase 2: DOR in RET-fusion Positive TC Participants With Specific RET Gene Status
Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR= disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to \<10 mm. PR=at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study (including baseline). DOR was analyzed using the KM method.
Time frame: Up to approximately 79.8 months
Phase 2: DOR
DOR was defined as the time from first documented response (CR/PR) to the date of first documented PD or death due to any cause, whichever occurs first. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). DOR was analyzed using the KM methods.
Time frame: Up to approximately 79.8 months
Phase 2: CBR
CBR was defined as the percentage of participants with CR or PR, or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). CBR and its two-sided 95% CI, which is based on the exact binomial distribution (Clopper-Pearson), were presented.
Time frame: Up to approximately 79.8 months
Phase 2: DCR
DCR was defined as the percentage of participants with a confirmed CR/PR, or SD, per RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). DCR and its two-sided 95% CI, which is based on the exact binomial distribution (Clopper-Pearson), were presented.
Time frame: Up to approximately 79.8 months
Phase 2: Progression-free Survival (PFS)
PFS was defined as the time from the first dose of pralsetinib to the date of first documented PD or death due to any cause, whichever occurred first. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). PFS was analyzed using KM methods.
Time frame: Up to approximately 7 years
Phase 2: Overall Survival (OS)
OS was defined as the time from the first dose of pralsetinib to the date of death due to any causes.
Time frame: Up to approximately 7 years
Phase 2: Intracranial ORR in RET-fusion Positive NSCLC Central Nervous System (CNS) Metastases Participants
ORR=percentage of participants with CR or PR for at least 2 assessments with at least 28 days apart \& no PD in between. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/or cerebellum identified at baseline \& disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR =at least a 30% decrease in the SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline \& if in the absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or the identification of new CNS/brain lesion. PD=either at least 20% increase in the SOD of target CNS/brain lesion, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of any CNS/brain lesion identified as RECIST 1.1 nontarget lesions at baseline, or the identification of new CNS/brain lesion.
Time frame: Up to approximately 79.8 months
Phase 2: Intracranial CBR in RET-fusion Positive NSCLC CNS Metastases Participants
CBR=percentage of participants with CR/PR/SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in 1 cycle) from first dose date. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/ cerebellum identified at baseline\&disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR=at least a 30% decrease in SOD of any CNS/brain lesion, identified as target lesions at baseline \& if in absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or identification of new CNS/brain lesion. SD=neither sufficient shrinkage for PR nor sufficient increase for PD for target/non-target CNS/brain lesion, taking as reference smallest SOD while on study. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion.
Time frame: Up to approximately 79.8 months
Phase 2: Intracranial DCR in RET-fusion Positive NSCLC CNS Metastases Participants
DCR=percentage of participants with a confirmed CR/PR, or SD. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/or cerebellum identified at baseline \& disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR =at least a 30% decrease in the SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline \& if in the absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or the identification of new CNS/brain lesion. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target/non-target CNS/brain lesion, taking as reference the smallest SOD while on study. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion.
Time frame: Up to approximately 79.8 months
Phase 2: Intracranial DOR in RET-fusion Positive NSCLC CNS Metastases Participants
DOR=time from first documented CR/PR to the date of first documented PD/death due to any cause, whichever occurs first. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/ cerebellum identified at baseline \& disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR=at least a 30% decrease in SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline \& if in absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or identification of new CNS/brain lesion. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion. DOR was analyzed using the KM methods.
Time frame: Up to approximately 79.8 months
Phase 1: Maximum Plasma Concentration (Cmax)
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
Time frame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 1: Time to Maximum Plasma Concentration (Tmax)
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
Time frame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 1: Time of Last Quantifiable Plasma Drug Concentration (Tlast)
The maximum values for Tlast slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol. Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
Time frame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC0-24)
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
Time frame: 24 hours postdose on Day 1 of Cycle 1 (1 cycle = 28 days)
Phase 1: Plasma Drug Concentration at 24 Hours Postdose (C24hr)
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
Time frame: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 1: Apparent Volume of Distribution (Vz/F)
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
Time frame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 1: Terminal Elimination Half-Life (t½)
The maximum values for t1/2 slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol. Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
Time frame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 1: Apparent Oral Clearance (CL/F)
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
Time frame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 1: Accumulation Ratio for Cmax (RCmax)
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
Time frame: 24 hours postdose on Day 15 of Cycle 1 (1 cycle = 28 days)
Phase 1: Accumulation Ratio for AUC (RAUC)
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
Time frame: 24 hours postdose on Day 15 of Cycle 1 (1 cycle = 28 days)
Phase 2: Cmax
Time frame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 2: Tmax
Time frame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 2: Tlast
The maximum values for Tlast slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol.
Time frame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 2: AUC0-24
Time frame: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 2: C24hr
Time frame: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 2: t½
The maximum values for t1/2 slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol.
Time frame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 2: CL/F
Time frame: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)
Phase 1: Percent Change From Baseline in Dual Specificity Phosphatase 6 (DUSP6)
The dose dependent change in a mitogen-activated protein kinases (MAPK) pathway expression signature was analyzed for all available samples of MTC and NSCLC participants. Participants with archived sample (used as baseline) and on treatment Cycle 2 Day 1 (1 cycle = 28 days) tumor tissues with greater than 20% tumor cells are included in the analysis. The changes in tumor biomarker DUSP6 levels was explored.
Time frame: Baseline, Week 4
Phase 1: Percent Change From Baseline in Sprout Receptor Tyrosine Kinase Signaling Antagonist 4 (SPRY4)
The dose dependent change in a MAPK pathway expression signature was analyzed for all available samples of MTC and NSCLC participants. Participants with archived sample (used as baseline) and on treatment Cycle 2 Day 1 (1 cycle = 28 days) tumor tissues with greater than 20% tumor cells are included in the analysis. The changes in tumor biomarker SPRY4 levels was explored.
Time frame: Baseline, Week 4
A total of 590 participants with rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), RET mutation-positive medullary thyroid cancer (also known as RET-mutant MTC), RET fusion-positive thyroid cancer (TC) and other advanced solid tumors took part in the study at 74 investigative sites across 13 countries from 17 March 2017 to 21 March 2024. The study was divided into two parts: Phase 1 (Dose Escalation) and Phase 2 (Dose Expansion).
| Milestone | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg | Phase II: Pralsetinib 400 mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Started | 2 | 6 | 5 | 13 | 11 | 12 | 4 | 5 | 4 | 528 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 2 | 6 | 5 | 13 | 11 | 12 | 4 | 5 | 4 | 528 |
| Withdrew: Adverse event | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
| Withdrew: Death | 1 | 4 | 2 | 2 | 5 | 2 | 1 | 4 | 3 | 240 |
| Withdrew: Initiation of another therapy | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 16 |
| Withdrew: Physician decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Progressive disease | 0 | 1 | 1 | 5 | 2 | 0 | 1 | 0 | 0 | 30 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 | 2 | 1 | 3 | 0 | 0 | 0 | 52 |
| Withdrew: Reason not specified | 0 | 1 | 0 | 4 | 3 | 6 | 2 | 0 | 1 | 181 |
MTD was defined as the highest tolerated dose of pralsetinib without causing dose limiting toxicities (DLTs). DLT was defined as any Grade ≥3 adverse event (AE) occurring during Cycle 1 during Phase 1 (dose escalation) that is not clearly caused by something other than pralsetinib. RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase.
| mg | Phase 1: All Participants QD |
|---|---|
| MTD | 400 |
| RP2D | 400 |
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.
| percentage of participants | Pralsetinib ≤ 300 mg QD | Pralsetinib 400 mg QD | Pralsetinib BID Dosing Schedule | Pralsetinib All Doses |
|---|---|---|---|---|
| AEs | 37 | 540 | 9 | 590 |
| SAEs | 26 | 381 | 7 | 416 |
ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) for at least two assessments with at least 28 days apart and no disease progression (PD) in between. Per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). ORR and its two-sided 95% CI, based on the exact binomial distribution (Clopper-Pearson), were presented.
| percentage of participants | RET- Fusion Positive NSCLC With Prior Platinum Treatment: | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment | RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment | RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment | RET-fusion Positive TC | RET-fusion Positive Solid Tumors Other Than NSCLC and TC | RET-altered Solid Tumors Previously Treated With RET Inhibitor | RET-mutation Positive Tumors Other Than MTC |
|---|---|---|---|---|---|---|---|---|---|
| Phase 2: Overall Response Rate (ORR) | 63.1 (54.2 to 71.4) | 73.9 (51.6 to 89.8) | 78.3 (69.2 to 85.7) | 56.7 (43.2 to 69.4) | 77.8 (66.4 to 86.7) | 85.2 (66.3 to 95.8) | 46.4 (27.5 to 66.1) | 19.0 (5.4 to 41.9) | 7.7 (0.99 to 36.0) |
ORR was defined as the percentage of participants with a confirmed CR or PR for at least two assessments with at least 28 days apart and no PD in between. Per RECIST v1.1, CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). ORR and its two-sided 95% CI, based on the exact binomial distribution (Clopper-Pearson), was presented.
| percentage of participants | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Phase 1: ORR | 0 (NA to NA) | 50.0 (11.8 to 88.2) | 40.0 (5.3 to 85.3) | 38.5 (13.9 to 68.4) | 45.5 (16.7 to 76.6) | 41.7 (15.2 to 72.3) | 25.0 (0.99 to 80.6) | 80.0 (28.4 to 99.5) | 75.0 (19.4 to 99.4) |
Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., Kinesin family member 5B (KIF5B), coiled-coil domain containing 6 (CCDC6), nuclear receptor coactivator 4 (NCOA4)). RET genotypes were determined by local testing and/or central analysis of circulating tumor deoxyribonucleic acid (ctDNA). ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.
| percentage of participants | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment |
|---|---|---|---|
| KIF5B | 63.7 (53.0 to 73.6) | 82.4 (56.6 to 96.2) | 78.9 (68.1 to 87.5) |
| CCDC6 | 68.0 (46.5 to 85.1) | 75.0 (19.4 to 99.4) | 84.2 (60.4 to 96.6) |
| NCOA4 | 100 (2.5 to 100) | — | — |
| Other | 46.2 (19.2 to 74.9) | 0 (NA to NA) | 63.6 (30.8 to 89.1) |
Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.
| percentage of participants | RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment | RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment |
|---|---|---|
| M918T | 53.7 (37.4 to 69.3) | 74.4 (58.8 to 86.5) |
| Cysteine Rich Domain | 46.2 (19.2 to 74.9) | 88.0 (68.8 to 97.5) |
| V804X | 100 (15.8 to 100) | 0 (NA to NA) |
| Other | 100 (39.8 to 100) | 66.7 (9.4 to 99.2) |
Oncogenic RET activation has been implicated as a driver in both MTC and differentiated TC (DTC). These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.
| percentage of participants | RET-fusion Positive TC |
|---|---|
| CCDC6 | 82.4 (56.6 to 96.2) |
| NCOA4 | 100 (54.1 to 100) |
| Other | 75.0 (19.4 to 99.4) |
Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR, or stable disease (SD) which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
| percentage of participants | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment |
|---|---|---|---|
| KIF5B | 76.9 (66.9 to 85.1) | 88.2 (63.6 to 98.5) | 81.6 (71.0 to 89.5) |
| CCDC6 | 76.0 (54.9 to 90.6) | 75.0 (19.4 to 99.4) | 84.2 (60.4 to 96.6) |
| NCOA4 | 100 (2.5 to 100) | — | — |
| Other | 53.8 (25.1 to 80.8) | 0 (NA to NA) | 63.6 (30.8 to 89.1) |
Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR, or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
| percentage of participants | RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment | RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment |
|---|---|---|
| M918T | 78.0 (62.4 to 89.4) | 86.0 (72.1 to 94.7) |
| Cysteine Rich Domain | 76.9 (46.2 to 95.0) | 96.0 (79.6 to 99.9) |
| V804X | 100 (15.8 to 100) | 100 (2.5 to 100) |
| Other | 100 (39.8 to 100) | 100 (29.2 to 100) |
Oncogenic RET activation has been implicated as a driver in both MTC and DTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
| percentage of participants | RET-fusion Positive TC |
|---|---|
| CCDC6 | 82.4 (56.6 to 96.2) |
| NCOA4 | 100 (54.1 to 100) |
| Other | 75.0 (19.4 to 99.4) |
Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
| percentage of participants | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment |
|---|---|---|---|
| KIF5B | 93.4 (86.2 to 97.5) | 94.1 (71.3 to 99.9) | 88.2 (78.7 to 94.4) |
| CCDC6 | 88.0 (68.8 to 97.5) | 100 (39.8 to 100) | 89.5 (66.9 to 98.7) |
| NCOA4 | 100 (2.5 to 100) | — | — |
| Other | 84.6 (54.6 to 98.1) | 50.0 (1.3 to 98.7) | 100 (71.5 to 100) |
Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
| percentage of participants | RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment | RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment |
|---|---|---|
| M918T | 95.1 (83.5 to 99.4) | 90.7 (77.9 to 97.4) |
| Cysteine Rich Domain | 92.3 (64.0 to 99.8) | 96.0 (79.6 to 99.9) |
| V804X | 100 (15.8 to 100) | 100 (2.5 to 100) |
| Other | 100 (39.8 to 100) | 100 (29.2 to 100) |
Oncogenic RET activation has been implicated as a driver in both MTC and DTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).
| percentage of participants | RET-fusion Positive TC |
|---|---|
| CCDC6 | 94.1 (71.3 to 99.9) |
| NCOA4 | 100 (54.1 to 100) |
| Other | 100 (39.8 to 100) |
Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5), CCDC6, NCOA4). RET genotypes were determined by local testing \&/or central analysis of circulating tumor deoxyribonucleic acid (ctDNA). DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR=disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to \<10 mm. PR=at least a 30% decrease in SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study. DOR was analyzed using the Kaplan-Meier (KM) method.
| months | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment |
|---|---|---|---|
| KIF5B | 15.1 (8.8 to 34.2) | 21.5 (9.3 to NA) | 9.2 (7.4 to 13.4) |
| CCDC6 | 46.7 (33.7 to NA) | 29.6 (11.3 to 47.9) | NA (14.7 to NA) |
| NCOA4 | 12.9 (NA to NA) | — | — |
| Other | 35.2 (10.6 to NA) | — | 41.2 (27.9 to NA) |
Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR= disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to \<10 mm. PR=at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study (including baseline). DOR was analyzed using the Kaplan-Meier (KM) method.
| months | RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment | RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment |
|---|---|---|
| M918T | 18.4 (15.1 to 25.8) | 51.8 (40.0 to NA) |
| Cysteine Rich Domain | 29.5 (8.8 to NA) | 36.8 (23.1 to NA) |
| V804X | 21.8 (14.2 to 29.4) | — |
| Other | NA (14.5 to NA) | NA (NA to NA) |
Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR= disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to \<10 mm. PR=at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study (including baseline). DOR was analyzed using the KM method.
| months | RET-fusion Positive TC |
|---|---|
| CCDC6 | NA (11.2 to NA) |
| NCOA4 | 15.2 (6.9 to NA) |
| Other | NA (23.6 to NA) |
DOR was defined as the time from first documented response (CR/PR) to the date of first documented PD or death due to any cause, whichever occurs first. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). DOR was analyzed using the KM methods.
| months | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment | RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment | RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment | RET-fusion Positive TC | RET-fusion Positive Solid Tumors Other Than NSCLC and TC | RET-altered Solid Tumors Previously Treated With RET Inhibitor | RET-mutation Positive Tumors Other Than MTC |
|---|---|---|---|---|---|---|---|---|---|
| Phase 2: DOR | 31.8 (15.1 to 40.4) | 22.6 (11.1 to 47.9) | 13.4 (9.4 to 21.7) | 21.7 (15.1 to 34.8) | 51.8 (36.8 to NA) | NA (12.9 to NA) | 11.1 (5.5 to 25.1) | NA (6.0 to NA) | 5.5 (NA to NA) |
CBR was defined as the percentage of participants with CR or PR, or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). CBR and its two-sided 95% CI, which is based on the exact binomial distribution (Clopper-Pearson), were presented.
| percentage of participants | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment | RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment | RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment | RET-fusion Positive TC | RET-fusion Positive Solid Tumors Other Than NSCLC and TC | RET-altered Solid Tumors Previously Treated With RET Inhibitor | RET-mutation Positive Tumors Other Than MTC |
|---|---|---|---|---|---|---|---|---|---|
| Phase 2: CBR | 74.6 (66.2 to 81.8) | 78.3 (56.3 to 92.5) | 80.2 (71.3 to 87.3) | 80.0 (67.7 to 89.2) | 90.3 (81.0 to 96.0) | 85.2 (66.3 to 95.8) | 60.7 (40.6 to 78.5) | 28.6 (11.3 to 52.2) | 23.1 (5.0 to 53.8) |
DCR was defined as the percentage of participants with a confirmed CR/PR, or SD, per RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). DCR and its two-sided 95% CI, which is based on the exact binomial distribution (Clopper-Pearson), were presented.
| percentage of participants | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment | RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment | RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment | RET-fusion Positive TC | RET-fusion Positive Solid Tumors Other Than NSCLC and TC | RET-altered Solid Tumors Previously Treated With RET Inhibitor | RET-mutation Positive Tumors Other Than MTC |
|---|---|---|---|---|---|---|---|---|---|
| Phase 2: DCR | 91.5 (85.4 to 95.7) | 91.3 (72.0 to 98.9) | 89.6 (82.2 to 94.7) | 95.0 (86.1 to 99.0) | 93.1 (84.5 to 97.7) | 96.3 (81.0 to 99.9) | 75.0 (55.1 to 89.3) | 42.9 (21.8 to 66.0) | 69.2 (38.6 to 90.9) |
PFS was defined as the time from the first dose of pralsetinib to the date of first documented PD or death due to any cause, whichever occurred first. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). PFS was analyzed using KM methods.
| months | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment | RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment | RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment | RET-fusion Positive TC | RET-fusion Positive Solid Tumors Other Than NSCLC and TC |
|---|---|---|---|---|---|---|---|
| Phase 2: Progression-free Survival (PFS) | 16.4 (11.4 to 23.5) | 13.0 (9.3 to 35.1) | 12.1 (9.2 to 16.6) | 24.9 (19.9 to 35.0) | 55.3 (37.2 to NA) | NA (14.7 to NA) | 7.0 (3.9 to 12.8) |
OS was defined as the time from the first dose of pralsetinib to the date of death due to any causes.
| months | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment | RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment | RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment | RET-fusion Positive TC | RET-fusion Positive Solid Tumors Other Than NSCLC and TC |
|---|---|---|---|---|---|---|---|
| Phase 2: Overall Survival (OS) | 39.7 (27.8 to 53.2) | 46.0 (19.1 to 62.4) | 50.1 (28.3 to NA) | 42.2 (31.2 to NA) | NA (NA to NA) | NA (19.4 to NA) | 10.3 (6.8 to 25.2) |
ORR=percentage of participants with CR or PR for at least 2 assessments with at least 28 days apart \& no PD in between. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/or cerebellum identified at baseline \& disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR =at least a 30% decrease in the SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline \& if in the absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or the identification of new CNS/brain lesion. PD=either at least 20% increase in the SOD of target CNS/brain lesion, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of any CNS/brain lesion identified as RECIST 1.1 nontarget lesions at baseline, or the identification of new CNS/brain lesion.
| percentage of participants | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment |
|---|---|---|---|
| Phase 2: Intracranial ORR in RET-fusion Positive NSCLC Central Nervous System (CNS) Metastases Participants | 53.8 (25.1 to 80.8) | 100 (2.5 to 100) | 0 (NA to NA) |
CBR=percentage of participants with CR/PR/SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in 1 cycle) from first dose date. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/ cerebellum identified at baseline\&disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR=at least a 30% decrease in SOD of any CNS/brain lesion, identified as target lesions at baseline \& if in absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or identification of new CNS/brain lesion. SD=neither sufficient shrinkage for PR nor sufficient increase for PD for target/non-target CNS/brain lesion, taking as reference smallest SOD while on study. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion.
| percentage of participants | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment |
|---|---|---|---|
| Phase 2: Intracranial CBR in RET-fusion Positive NSCLC CNS Metastases Participants | 61.5 (31.6 to 86.1) | 100 (2.5 to 100) | 0 (NA to NA) |
DCR=percentage of participants with a confirmed CR/PR, or SD. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/or cerebellum identified at baseline \& disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR =at least a 30% decrease in the SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline \& if in the absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or the identification of new CNS/brain lesion. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target/non-target CNS/brain lesion, taking as reference the smallest SOD while on study. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion.
| percentage of participants | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment |
|---|---|---|---|
| Phase 2: Intracranial DCR in RET-fusion Positive NSCLC CNS Metastases Participants | 76.9 (46.2 to 95.0) | 100 (2.5 to 100) | 0 (NA to NA) |
DOR=time from first documented CR/PR to the date of first documented PD/death due to any cause, whichever occurs first. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/ cerebellum identified at baseline \& disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR=at least a 30% decrease in SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline \& if in absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or identification of new CNS/brain lesion. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion. DOR was analyzed using the KM methods.
| months | RET- Fusion Positive NSCLC With Prior Platinum Treatment | RET-fusion Positive NSCLC With Non-platinum Systemic Treatment | RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment |
|---|---|---|---|
| Phase 2: Intracranial DOR in RET-fusion Positive NSCLC CNS Metastases Participants | 28.3 (10.5 to NA) | 11.3 (NA to NA) | — |
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
| nanograms per milliliters (ng/mL) | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 1 | 346 ± NA | 335 ± 52.8 | 198 ± 99.8 | 459 ± 52.3 | 688 ± 53.3 | 1210 ± 85.3 | 1820 ± 63.8 | 569 ± 42.0 | 715 ± 64.1 |
| Cycle 1 Day 15 | 130 ± NA | 420 ± 56.9 | 586 ± 47.8 | 525 ± 72.5 | 1390 ± 35.3 | 1930 ± 66.7 | 4330 ± NA | 1080 ± 43.8 | 1780 ± NA |
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
| hour | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 1 | 3.04 (2.08 to 4.00) | 2.04 (1.98 to 4.00) | 2.03 (2.00 to 6.03) | 2.07 (0.983 to 7.98) | 2.02 (1.72 to 7.90) | 3.00 (2.00 to 6.03) | 2.00 (2.00 to 2.00) | 12.5 (12.2 to 14.8) | 12.0 (2.07 to 12.3) |
| Cycle 1 Day 15 | 1.87 (1.87 to 1.87) | 2.00 (1.97 to 4.13) | 3.97 (3.90 to 4.00) | 2.97 (1.05 to 4.08) | 2.23 (0.983 to 24.0) | 3.03 (2.00 to 7.85) | 6.00 (4.00 to 8.00) | 2.00 (0.500 to 3.95) | 4.03 (1.98 to 6.08) |
The maximum values for Tlast slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol. Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
| hours | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 1 | 24.0 (24.0 to 24.0) | 24.0 (23.1 to 24.4) | 24.0 (7.88 to 24.1) | 24.0 (21.9 to 25.7) | 23.8 (7.88 to 24.0) | 23.8 (22.6 to 24.6) | 23.9 (23.4 to 24.0) | 12.5 (12.2 to 14.8) | 12.3 (12.0 to 14.4) |
| Cycle 1 Day 15 | 23.8 (23.8 to 23.8) | 24.1 (23.9 to 24.4) | 24.3 (23.6 to 27.8) | 24.0 (8.00 to 26.6) | 24.0 (22.2 to 24.8) | 24.0 (7.38 to 25.4) | 24.1 (24.0 to 24.2) | 12.2 (7.88 to 15.7) | 12.5 (10.1 to 14.8) |
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
| hours*nanograms/milliliter (hours*ng/ml) | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Phase 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC0-24) | 4450 ± NA | 3620 ± 50.8 | 3010 ± 84.8 | 5260 ± 46.2 | 8470 ± 54.5 | 14700 ± 60.3 | 27700 ± 94.1 | — | — |
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
| ng/mL | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 1 | 110 ± NA | 69.2 ± 81.0 | 65.8 ± 59.6 | 104 ± 76.6 | 221 ± 64.2 | 376 ± 74.1 | 715 ± 75.9 | — | — |
| Cycle 1 Day 15 | 55.9 ± NA | 94.2 ± 123 | 175 ± 31.3 | 137 ± 132 | 713 ± 42.2 | 977 ± 107 | 1950 ± NA | — | — |
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
| liters | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 1 | 96.1 ± NA | 230 ± 37.1 | 458 ± 125 | 499 ± 50.8 | 543 ± 82.6 | 430 ± 62.6 | 350 ± 115 | — | — |
| Cycle 1 Day 15 | 355 ± NA | 171 ± 176 | 232 ± 43.7 | 622 ± 67.3 | 367 ± 86.6 | 418 ± 19.9 | 181 ± NA | — | — |
The maximum values for t1/2 slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol. Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
| hours | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 1 | 16.3 (11.8 to 20.8) | 9.87 (8.98 to 18.3) | 14.3 (8.12 to 31.5) | 12.6 (6.69 to 34.9) | 12.2 (9.53 to 34.5) | 16.5 (10.2 to 48.7) | 19.7 (12.8 to 36.1) | — | 10.7 (10.7 to 10.7) |
| Cycle 1 Day 15 | 17.6 (17.6 to 17.6) | 8.10 (5.25 to 39.6) | 13.4 (12.5 to 14.4) | 13.2 (10.1 to 21.8) | 20.4 (9.91 to 27.3) | 20.9 (9.21 to 33.6) | 13.0 (13.0 to 13.0) | — | — |
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
| liters per hour (L/hr) | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 1 | 4.26 ± NA | 14.7 ± 42.3 | 20.6 ± 48.1 | 27.3 ± 60.3 | 23.3 ± 40.2 | 15.2 ± 88.1 | 11.6 ± 81.3 | — | — |
| Cycle 1 Day 15 | 14.0 ± NA | 11.3 ± 51.2 | 12.0 ± 38.9 | 31.4 ± 97.8 | 13.2 ± 33.0 | 11.1 ± 72.2 | 8.57 ± NA | — | — |
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
| ratio | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Phase 1: Accumulation Ratio for Cmax (RCmax) | 1.04 ± NA | 1.25 ± 27.6 | 3.20 ± 114 | 1.17 ± 110 | 1.87 ± 40.5 | 1.62 ± 102 | 2.97 ± NA | 1.91 ± 40.7 | 1.41 ± NA |
Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.
| ratio | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Phase 1: Accumulation Ratio for AUC (RAUC) | 1.43 ± NA | 1.47 ± 11.1 | 3.22 ± NA | 1.31 ± 147 | 2.33 ± 11.4 | 2.75 ± 70.9 | 2.48 ± NA | 4.28 ± NA | 1.21 ± NA |
| ng/mL | RET- Fusion Positive NSCLC Participants | Tumor-agnostic Participants | RET-altered Solid Tumors Participants | RET-mutation Positive Tumors Other Than MTC Participants |
|---|---|---|---|---|
| Cycle 1 Day 1 | 1680 ± 69.4 | 1380 ± 65.4 | 2450 ± 164 | 1770 ± 87.2 |
| Cycle 1 Day 15 | 2840 ± 50.7 | 2200 ± 36.7 | 3440 ± 93.9 | 2430 ± 55.3 |
| hours | RET- Fusion Positive NSCLC Participants | Tumor-agnostic Participants | RET-altered Solid Tumors Participants | RET-mutation Positive Tumors Other Than MTC Participants |
|---|---|---|---|---|
| Cycle 1 Day 1 | 4.00 (1.90 to 23.7) | 3.90 (2.0 to 6.0) | 4.0 (4.0 to 6.0) | 2.05 (2 to 8) |
| Cycle 1 Day 15 | 4.00 (1.00 to 8.10) | 5.00 (2.0 to 8.0) | 4.00 (2.00 to 6.00) | 3.05 (2 to 6) |
The maximum values for Tlast slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol.
| hours | RET- Fusion Positive NSCLC Participants | Tumor-agnostic Participants | RET-altered Solid Tumors Participants | RET-mutation Positive Tumors Other Than MTC Participants |
|---|---|---|---|---|
| Cycle 1 Day 1 | 23.9 (2.40 to 24.8) | 8.00 (7.8 to 23.5) | 23.10 (8.0 to 24.0) | 8.05 (8.0 to 24.0) |
| Cycle 1 Day 15 | 23.8 (7.80 to 26.5) | 23.70 (7.9 to 24.0) | 24.00 (7.9 to 24.0) | 24.00 (23.8 to 24.0) |
| hours*ng/mL | RET- Fusion Positive NSCLC Participants | Tumor-agnostic Participants | RET-altered Solid Tumors Participants | RET-mutation Positive Tumors Other Than MTC Participants |
|---|---|---|---|---|
| Cycle 1 Day 1 | 20400 ± 64.2 | 17400 ± 152 | 103000 ± NA | 18400 ± 69.8 |
| Cycle 1 Day 15 | 40100 ± 59.5 | 33900 ± 27.4 | 91100 ± 46.8 | 32000 ± 90.8 |
| ng/mL | RET- Fusion Positive NSCLC Participants | Tumor-agnostic Participants | RET-altered Solid Tumors Participants | RET-mutation Positive Tumors Other Than MTC Participants |
|---|---|---|---|---|
| Cycle 1 Day 1 | 540 ± 75.4 | 519 ± 197 | 1020 ± 225 | 415 ± 140 |
| Cycle 1 Day 15 | 1150 ± 69 | 797 ± 42.8 | 1400 ± 207 | 1050 ± 94.0 |
The maximum values for t1/2 slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol.
| hours | RET- Fusion Positive NSCLC Participants | Tumor-agnostic Participants | RET-altered Solid Tumors Participants | RET-mutation Positive Tumors Other Than MTC Participants |
|---|---|---|---|---|
| Cycle 1 Day 1 | 13.4 ± 44.1 | 18.4 ± 98.8 | 20.8 ± NA | 11.0 ± 55.8 |
| Cycle 1 Day 15 | 17.9 ± 58.8 | 16.5 ± 44.6 | 25.8 ± NA | 63.0 ± 882 |
| liters per hour (L/hour) | RET- Fusion Positive NSCLC Participants | Tumor-agnostic Participants | RET-altered Solid Tumors Participants | RET-mutation Positive Tumors Other Than MTC Participants |
|---|---|---|---|---|
| Cycle 1 Day 1 | 13.4 ± 56.8 | 12.7 ± 347 | 2.00 ± NA | 16.1 ± 43.3 |
| Cycle 1 Day 15 | 9.91 ± 58.9 | 7.49 ± 64.4 | 2.92 ± NA | 1.39 ± 1220 |
The dose dependent change in a mitogen-activated protein kinases (MAPK) pathway expression signature was analyzed for all available samples of MTC and NSCLC participants. Participants with archived sample (used as baseline) and on treatment Cycle 2 Day 1 (1 cycle = 28 days) tumor tissues with greater than 20% tumor cells are included in the analysis. The changes in tumor biomarker DUSP6 levels was explored.
| percent change | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Phase 1: Percent Change From Baseline in Dual Specificity Phosphatase 6 (DUSP6) | 0 ± 0 | 54.26 ± 88.318 | 0 ± 0 | -20.27 ± 42.971 | -74.87 ± 15.707 | -13.32 ± 82.394 | 0 ± 0 | -81.57 ± 3.057 | -61.96 ± 39.141 |
The dose dependent change in a MAPK pathway expression signature was analyzed for all available samples of MTC and NSCLC participants. Participants with archived sample (used as baseline) and on treatment Cycle 2 Day 1 (1 cycle = 28 days) tumor tissues with greater than 20% tumor cells are included in the analysis. The changes in tumor biomarker SPRY4 levels was explored.
| percent change | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg |
|---|---|---|---|---|---|---|---|---|---|
| Phase 1: Percent Change From Baseline in Sprout Receptor Tyrosine Kinase Signaling Antagonist 4 (SPRY4) | 0 ± 0 | 210.16 ± 309.468 | 0 ± 0 | -34.98 ± 29.569 | -69.00 ± 28.731 | -3.26 ± 99.349 | 0 ± 0 | -75.65 ± 10.944 | 124.93 ± 311.210 |
Collected over AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Pralsetinib ≤ 300 mg QD | 15/37 (40.5%) | 26/37 (70.3%) | 36/37 (97.3%) |
| Pralsetinib 400 mg QD | 245/540 (45.4%) | 381/540 (70.6%) | 536/540 (99.3%) |
| Pralsetinib BID Dosing Schedule | 7/9 (77.8%) | 7/9 (77.8%) | 9/9 (100%) |
| Pralsetinib All Doses | 268/590 (45.4%) | 416/590 (70.5%) | 585/590 (99.2%) |
| Event | Pralsetinib ≤ 300 mg QD | Pralsetinib 400 mg QD | Pralsetinib BID Dosing Schedule | Pralsetinib All Doses |
|---|---|---|---|---|
| SepsisInfections and infestations | 2/37 | 20/540 | 3/9 | 25/590 |
| PneumoniaInfections and infestations | 5/37 | 87/540 | 1/9 | 94/590 |
| AnaemiaBlood and lymphatic system disorders | 1/37 | 32/540 | 1/9 | 34/590 |
| Cardiac arrestCardiac disorders | 1/37 | 0/540 | 1/9 | 2/590 |
| Abdominal painGastrointestinal disorders | 0/37 | 7/540 | 1/9 | 8/590 |
| Abdominal pain upperGastrointestinal disorders | 0/37 | 2/540 | 1/9 | 3/590 |
| Gastrointestinal haemorrhageGastrointestinal disorders | 0/37 | 7/540 | 1/9 | 8/590 |
| StomatitisGastrointestinal disorders | 0/37 | 3/540 | 1/9 | 4/590 |
| CalcinosisGeneral disorders | 0/37 | 0/540 | 1/9 | 1/590 |
| Escherichia bacteraemiaInfections and infestations | 0/37 | 0/540 | 1/9 | 1/590 |
| Event | Pralsetinib ≤ 300 mg QD | Pralsetinib 400 mg QD | Pralsetinib BID Dosing Schedule | Pralsetinib All Doses |
|---|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 16/37 | 285/540 | 6/9 | 310/590 |
| Aspartate aminotransferase increasedInvestigations | 17/37 | 273/540 | 3/9 | 295/590 |
| DiarrhoeaGastrointestinal disorders | 10/37 | 189/540 | 4/9 | 207/590 |
| Oedema peripheralGeneral disorders | 9/37 | 104/540 | 4/9 | 117/590 |
| HypertensionVascular disorders | 9/37 | 189/540 | 4/9 | 206/590 |
| ConstipationGastrointestinal disorders | 12/37 | 238/540 | 2/9 | 255/590 |
| Alanine aminotransferase increasedInvestigations | 16/37 | 212/540 | 3/9 | 232/590 |
| White blood cell count decreasedInvestigations | 14/37 | 157/540 | 2/9 | 175/590 |
| PyrexiaGeneral disorders | 7/37 | 164/540 | 3/9 | 176/590 |
| Blood creatinine increasedInvestigations | 11/37 | 143/540 | 3/9 | 158/590 |
Safety population included all participants who had received at least 1 dose of the study drug regardless of the starting dose levels.
| Age, Continuous(years) | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg | Phase II: Pralsetinib 400 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 54.5 ± 9.2 | 49.5 ± 18.0 | 51.2 ± 13.2 | 53.8 ± 13.6 | 60.6 ± 11.0 | 49.2 ± 17.8 | 59.5 ± 9.1 | 63.0 ± 11.09 | 61.8 ± 18.25 | 57.7 ± 12.6 | 57.5 ± 12.8 |
| Sex: Female, Male(Participants) | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg | Phase II: Pralsetinib 400 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | 1 | 3 | 4 | 5 | 4 | 3 | 3 | 1 | 2 | 257 | 283 |
| Male | 1 | 3 | 1 | 8 | 7 | 9 | 1 | 4 | 2 | 271 | 307 |
| Ethnicity (NIH/OMB)(Participants) | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg | Phase II: Pralsetinib 400 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 2 | 2 | 1 | 1 | 0 | 3 | 0 | 0 | 0 | 19 | 28 |
| Not Hispanic or Latino | 0 | 4 | 4 | 12 | 11 | 9 | 4 | 3 | 4 | 465 | 516 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 44 | 46 |
| Race/Ethnicity, Customized(Participants) | Phase I: Pralsetinib 30 mg | Phase I: Pralsetinib 60 mg | Phase I: Pralsetinib 100 mg | Phase I: Pralsetinib 200 mg | Phase I: Pralsetinib 300 mg | Phase I: Pralsetinib 400 mg | Phase I: Pralsetinib 600 mg | Phase I: Pralsetinib 100/100 mg | Phase I: Pralsetinib 200/100 mg | Phase II: Pralsetinib 400 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Asian | 0 | 1 | 2 | 0 | 0 | 2 | 0 | 1 | 0 | 203 | 209 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 |
| Black or African American | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 4 | 6 |
| White | 0 | 3 | 2 | 11 | 11 | 9 | 4 | 3 | 4 | 284 | 331 |
| Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 |
| Unknown or Not Reported | 2 | 2 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 32 | 39 |
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Studies of the drug tested here: Pralsetinib