A Phase 2 interventional study of NIR178 and PDR001 in NSCLC, Non Small Cell Lung Cancer, RCC, Renal Cell Cancer and Pancreatic Cancer, sponsored by Novartis Pharmaceuticals. Terminated at 21 sites in 15 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-09.
Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment
The purpose of this phase 2 study is to evaluate the efficacy and safety of NIR178 in combination with PDR001 in multiple solid tumors and diffuse large B-cell lymphoma (DLBCL) and further explore schedule variations of NIR178 to optimize immune activation through inhibition of A2aR.
This is an open-label multi-part, phase II study evaluating the combination of NIR178 and PDR001 in patients with advanced solid tumors and diffuse large B cell lymphoma (DLBCL).
The study has three parts:
In addition, a separate safety run-in part was conducted in Japan in order to adequately characterize the safety and pharmacokinetic profiles of NIR178 as a single-agent and in combination with PDR001.
Patients enrolled in this study received NIR178 either twice daily (BID) continuously or based on the assigned intermittent schedule within 60 minutes prior to PDR001 infusion. PDR001 400 mg was administered via IV infusion over 30 minutes once every 4 weeks. Each treatment cycle was 28 days. Patients enrolled in the Japanese safety run-in part received NIR178 as single agent for the first cycle (28 days). If the patients completed Cycle 1 without experiencing dose limiting toxicities (DLTs), they initiated combination therapy with PDR001 starting Cycle 2 onwards, and continued at the same dose of NIR178. An additional cohort in the Japanese safety run-in part of the study received NIR178 in combination with PDR001 starting with Cycle 1. If the patients complete Cycle 1 without experiencing DLTs, they continued to receive combination treatment.
Patients received treatment with the combination until disease progression (assessed by investigator per immune-related response criteria (iRECIST) or Cheson 2014), unacceptable toxicity, death or discontinuation from study treatment for any other reason (e.g., withdrawal of consent, start of a new anti-neoplastic therapy or at the discretion of the investigator), otherwise known as End of Treatment.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 315 is above the median of 40 across 4,509 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
The collection of recent sample is permitted under the following conditions (both must be met):
Biopsy was collected ≤ 6 months before 1st dose of study treatment and available at the site.
No immunotherapy was given to the patient since collection of biopsy.
Patients with head and neck cancer must have received a prior platinum-containing regimen.
Patients with bladder cancer must have received a prior platinum-containing regimen or be ineligible for cisplatin.
Patients with renal cell carcinoma must have received a prior VEGF tyrosine kinase inhibitor (TKI).
Patients with MSS colorectal cancer must have received (or be intolerant to) prior therapy with fluoropyrimidine-oxaliplatin- and irinotecan- based regimens.
Patients with triple negative breast cancer:. Part 1: must have received a prior taxane-containing regimen Part 3: should have received no more than 2 prior lines of therapy including taxane-based chemotherapy and should have a known PD-L1 status as per local available testing as determined by VENTANA PD-L1 SP142 Assay with IC score of 0 (\<1%) Patients with DLBCL should be limited to those with no available therapies of proven clinical benefit Patients should have had prior autologous hematopoietic stem cell transplantation (auto-HSCT) or determined to be ineligible for auto-HSCT.
Patients with melanoma:
BRAF V600E wild type patients: must have received anti-PD-1/PD-L1 single agent, or in combination with anti-CTLA-4 therapy BRAF V600E mutant patients: must have received prior anti-PD-1/PD-L1 single-agent, or in combination with anti-CTLA-4 therapy. In addition, subjects must have received prior BRAF V600E inhibitor therapy, either single-agent or in combination with a MEK inhibitor
Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC):
Exclusion Criteria:
Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of study drug and of low potential risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease
Part 1: NIR178 continuously in combination with PDR001 400mg every 4 weeks. The part 1 enrolled 9 different tumor types.
Drug: NIR178 · Drug: PDR001
Part 2: Three different dosing schedules of NIR178 twice daily (BID) including continuous and two intermittent in combination with PDR001
Drug: NIR178 · Drug: PDR001
Further evaluation of optimal intermittent or continuous schedule of NIR178 in combination with PDR001 (if selected based on results of Part 2). A film-coated tablet of NIR178 was assessed.
Drug: NIR178 · Drug: PDR001
Different dosing schedules of NIR178 were explored.
Drug: NIR178 · Drug: PDR001
NIR178, a new, non-xanthine based compound, is a potent oral adenosine A2a receptor against antagonist being developed by Novartis. NIR178 was administered orally twice daily (BID) as a capsule (Part 1, Part 2 and Japanese safety run-in) and as a film-coated table (Part 3). There were up to 3 dose levels assessed: 80, 160 and 240 mg. Three alternative dosing schedules were evaluated: continuous (Part 1, Part 2, Part 3, Japanese safety run-in), 2 weeks on/2 weeks off (Part 2) and 1 week on/1 week off (Part 2). Each cycle consisted of 28 days.
Also known as: taminadenant
PDR001 is a human monoclonal antibody (MAb) administered on Day 1 of each cycle. PDR001 400 mg was administered via intravenous (i.v.) infusion over 30 minutes every 4 weeks (Q4W).
Also known as: spartalizumab
Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to 3.9 years
Part 1: Overall Response Rate (ORR) Per Cheson 2014 for DLBCL
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL). For Cheson 2014 criteria, CR= Target nodes/nodal masses must regress to ≤1.5 cm in longest diameter (LDi), no extralymphatic sites of disease, absent non-measured lesions, organ enlargement regress to normal, no new lesions, and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative); PR= ≥50% decrease in the sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes, absent or regressed non-measured lesions, spleen must have regressed by \>50% in length beyond normal, and no new lesions.
Time frame: Up to 2.5 years
Part 2: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to 4.7 years
Part 3: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to 0.5 years
Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 3.9 years
Part 2: Overall Response Rate (ORR) Per iRECIST for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 4.7 years
Part 3: Overall Response Rate (ORR) Per iRECIST for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 0.5 years
Part 1: Mean Percentage Change in PSA From Baseline
Prostate-specific antigen (PSA) levels were assessed in serum. Rising PSA is generally a manifestation of progression of prostate cancer.
Time frame: Baseline, up to 0.8 years
Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
Time frame: Up to 3.9 years
Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 3.9 years
Part 1: Disease Control Rate (DCR) Per Cheson 2014 for DLBCL
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL).
Time frame: Up to 2.5 years
Part 2: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
Time frame: Up to 4.7 years
Part 2: Disease Control Rate (DCR) Per iRECIST for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 4.7 years
Part 3: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
Time frame: Up to 0.5 years
Part 3: Disease Control Rate (DCR) Per iRECIST for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 0.5 years
Part 1: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 3.9 years
Part 1: Duration Of Response (DOR) Per iRECIST for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 3.9 years
Part 1: Duration Of Response (DOR) Per Cheson 2014 for DLBCL
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per Cheson 2014 criteria for DLBCL. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 2.5 years
Part 2: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 4.7 years
Part 2: Duration Of Response (DOR) Per iRECIST for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 4.7 years
Part 3: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 0.5 years
Part 3: Duration Of Response (DOR) Per iRECIST for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 0.5 years
Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 3.9 years
Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 3.9 years
Part 1: Progression-Free Survival (PFS) Per Cheson 2014 for DLBCL
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per Cheson 2014 for DLBCL. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 2.5 years
Part 2: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 4.7 years
Part 2: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 4.7 years
Part 3: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 0.5 years
Part 3: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 0.5 years
Part 1: 2-year Overall Survival (OS)
OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan (SAP).
Time frame: 2 years
Part 2: 2-year Overall Survival (OS)
OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan.
Time frame: 2 years
Part 3: 2-year Overall Survival (OS)
OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan.
Time frame: 2 years
Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue
The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
Time frame: Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days.
Part 2: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue
The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
Time frame: Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days.
Part 3: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue
The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
Time frame: Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days.
Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period
Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.
Time frame: Up to 4 years (Part 1), 4.8 years (Part 2) and 0.6 years (Part 3)
Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178
Number of participants with at least one dose reduction of NIR178 and number of participants with at least one dose interruption of NIR178. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
Time frame: Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001
Number of participants with at least one dose reduction of PDR001 and number of participants with at least one dose interruption of PDR001. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule. Dose reductions were not permitted for PDR001.
Time frame: Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
Part 1, 2 and 3: Dose Intensity of NIR178
Dose intensity of NIR178 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days.
Time frame: Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
Part 1, 2 and 3: Dose Intensity of PDR001
Dose intensity of PDR001 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and then multiplied by 28 days.
Time frame: Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies
PDR001 immunogenicity was evaluated in serum samples. Patient anti-drug antibodies (ADA) status was defined as follows: * ADA-negative at baseline: ADA-negative sample at baseline * ADA-positive at baseline: ADA-positive sample at baseline * ADA-negative post-baseline: ADA-negative sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples * Treatment-reduced ADA-positive: ADA-positive sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples * Treatment-induced ADA-positive: ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample * Treatment-boosted ADA-positive: ADA-positive sample at baseline and at least 1 treatment-boosted ADA-positive sample * ADA-inconclusive: patient who does not qualify for any of the above definitions or a patient for which the baseline sample is missing
Time frame: Up to approximately 5 years
Japan Safety Run-in: Number of Participants With Dose-Limiting Toxicities (DLTs)
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first 28 days of treatment with NIR178 as single agent or in combination with PDR001 during the Japan safety run-in part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Time frame: 28 days
Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period
Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.
Time frame: Up to 0.7 years
All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178
Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178
Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178
PK parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite)
NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite)
NJI765 is a NIR178 metabolite. Pharmacokinetic (PK) parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite)
NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
All Study Parts: Maximum Observed Serum Concentration (Cmax) of PDR001
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Time frame: First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days
All Study Parts: Time to Reach Maximum Serum Concentration (Tmax) of PDR001
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Time frame: First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days
All Study Parts: Area Under the Serum Concentration-time Curve From Time Zero to 28 Days Post Dose (AUC0-28day) of PDR001
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-28day calculation.
Time frame: First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days
Participants took part in 21 investigative sites in 15 countries.
| Milestone | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: MSS CRC Unk 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 11 | 12 | 11 | 14 | 14 | 15 | 11 | 12 | 27 | 29 | 2 | 30 | 3 | 13 | 13 | 6 | 15 | 22 | 20 | 20 | 6 | 3 | 3 | 3 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 11 | 12 | 11 | 14 | 14 | 15 | 11 | 12 | 27 | 29 | 2 | 30 | 3 | 13 | 13 | 6 | 15 | 22 | 20 | 20 | 6 | 3 | 3 | 3 |
| Withdrew: Adverse event | 1 | 0 | 1 | 0 | 0 | 2 | 1 | 1 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 2 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 1 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Physician decision | 3 | 5 | 0 | 3 | 2 | 0 | 0 | 0 | 4 | 2 | 0 | 4 | 0 | 0 | 2 | 1 | 1 | 2 | 1 | 3 | 0 | 0 | 0 | 0 |
| Withdrew: Progressive disease | 7 | 7 | 9 | 10 | 11 | 10 | 9 | 8 | 19 | 23 | 2 | 24 | 3 | 11 | 9 | 5 | 10 | 14 | 13 | 14 | 6 | 3 | 3 | 3 |
| Withdrew: Patient/guardian decision | 0 | 0 | 1 | 1 | 1 | 2 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 2 | 0 | 1 | 3 | 4 | 1 | 0 | 0 | 0 | 0 |
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
| percentage of participants | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: mCRPC 240 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 27.3 (7.9 to 56.4) | 25.0 (7.2 to 52.7) | 0 (0.0 to 23.8) | 0 (0.0 to 19.3) | 7.1 (0.4 to 29.7) | 13.3 (2.4 to 36.3) | 0 (0.0 to 23.8) | 0 (0.0 to 10.5) | 3.4 (0.2 to 15.3) | 10.0 (2.8 to 23.9) | 0 (0.0 to 20.6) | 0 (0.0 to 18.1) |
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL). For Cheson 2014 criteria, CR= Target nodes/nodal masses must regress to ≤1.5 cm in longest diameter (LDi), no extralymphatic sites of disease, absent non-measured lesions, organ enlargement regress to normal, no new lesions, and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative); PR= ≥50% decrease in the sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes, absent or regressed non-measured lesions, spleen must have regressed by \>50% in length beyond normal, and no new lesions.
| percentage of participants | Part 1: DLBCL 160 mg |
|---|---|
| Part 1: Overall Response Rate (ORR) Per Cheson 2014 for DLBCL | 15.4 (2.8 to 41.0) |
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
| percentage of participants | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off |
|---|---|---|---|
| Part 2: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 9.1 (1.6 to 25.9) | 0 (0.0 to 13.9) | 10.0 (1.8 to 28.3) |
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
| percentage of participants | Part 3: TNBC 160 mg Cont |
|---|---|
| Part 3: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 16.7 (0.9 to 58.2) |
ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
| percentage of participants | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: mCRPC 240 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 36.4 (13.5 to 65.0) | 25.0 (7.2 to 52.7) | 0 (0.0 to 23.8) | 0 (0.0 to 19.3) | 7.1 (0.4 to 29.7) | 13.3 (2.4 to 36.3) | 0 (0.0 to 23.8) | 0 (0.0 to 10.5) | 3.4 (0.2 to 15.3) | 10.0 (2.8 to 23.9) | 0 (0.0 to 20.6) | 0 (0.0 to 18.1) |
ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
| percentage of participants | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off |
|---|---|---|---|
| Part 2: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 9.1 (1.6 to 25.9) | 5.0 (0.3 to 21.6) | 15.0 (4.2 to 34.4) |
ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
| percentage of participants | Part 3: TNBC 160 mg Cont |
|---|---|
| Part 3: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 16.7 (0.9 to 58.2) |
Prostate-specific antigen (PSA) levels were assessed in serum. Rising PSA is generally a manifestation of progression of prostate cancer.
| percentage change in PSA from baseline | Part 1: mCRPC 240 mg |
|---|---|
| Part 1: Mean Percentage Change in PSA From Baseline | 214.46 ± 329.459 |
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
| percentage of participants | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: mCRPC 240 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 54.5 (27.1 to 80.0) | 66.7 (39.1 to 87.7) | 18.2 (3.3 to 47.0) | 0 (0.0 to 19.3) | 28.6 (10.4 to 54.0) | 40.0 (19.1 to 64.0) | 63.6 (35.0 to 86.5) | 25.9 (12.9 to 43.2) | 17.2 (7.0 to 32.9) | 33.3 (19.3 to 49.9) | 0 (0.0 to 20.6) | 46.7 (24.4 to 70.0) |
DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
| percentage of participants | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: mCRPC 240 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 63.6 (35.0 to 86.5) | 66.7 (39.1 to 87.7) | 18.2 (3.3 to 47.0) | 0 (0.0 to 19.3) | 35.7 (15.3 to 61.0) | 40.0 (19.1 to 64.0) | 54.5 (27.1 to 80.0) | 25.9 (12.9 to 43.2) | 13.8 (4.9 to 28.8) | 36.7 (22.1 to 53.3) | 0 (0.0 to 20.6) | 46.7 (24.4 to 70.0) |
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL).
| percentage of participants | Part 1: DLBCL 160 mg |
|---|---|
| Part 1: Disease Control Rate (DCR) Per Cheson 2014 for DLBCL | 23.1 (6.6 to 49.5) |
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
| percentage of participants | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off |
|---|---|---|---|
| Part 2: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 36.4 (19.6 to 56.1) | 40.0 (21.7 to 60.6) | 35.0 (17.7 to 55.8) |
DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
| percentage of participants | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off |
|---|---|---|---|
| Part 2: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 36.4 (19.6 to 56.1) | 45.0 (25.9 to 65.3) | 45.0 (25.9 to 65.3) |
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
| percentage of participants | Part 3: TNBC 160 mg Cont |
|---|---|
| Part 3: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 16.7 (0.9 to 58.2) |
DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
| percentage of participants | Part 3: TNBC 160 mg Cont |
|---|---|
| Part 3: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 16.7 (0.9 to 58.2) |
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: mCRPC 240 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA (NA to NA) | NA (NA to NA) | — | — | NA (NA to NA) | NA (NA to NA) | — | — | NA (NA to NA) | NA (NA to NA) | — | — |
DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: mCRPC 240 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA (NA to NA) | NA (NA to NA) | — | — | NA (NA to NA) | NA (NA to NA) | — | — | NA (NA to NA) | NA (NA to NA) | — | — |
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per Cheson 2014 criteria for DLBCL. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 1: DLBCL 160 mg |
|---|---|
| Part 1: Duration Of Response (DOR) Per Cheson 2014 for DLBCL | NA (NA to NA) |
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off |
|---|---|---|---|
| Part 2: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA (NA to NA) | — | NA (NA to NA) |
DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off |
|---|---|---|---|
| Part 2: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) |
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 3: TNBC 160 mg Cont |
|---|---|
| Part 3: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA (NA to NA) |
DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 3: TNBC 160 mg Cont |
|---|---|
| Part 3: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA (NA to NA) |
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: mCRPC 240 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 3.5 (1.9 to 15.4) | 7.2 (1.8 to 8.6) | 1.9 (1.7 to 2.0) | 1.7 (1.6 to 1.7) | 1.9 (1.7 to 3.5) | 2.0 (1.6 to 3.7) | 3.5 (1.7 to 3.7) | 1.7 (1.6 to 1.9) | 1.9 (1.7 to 2.0) | 1.7 (1.6 to 1.9) | 1.8 (1.6 to 1.9) | 3.7 (1.7 to 5.3) |
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: mCRPC 240 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 8.7 (2.1 to NA) | 7.2 (1.8 to NA) | 1.9 (1.7 to 2.0) | 1.7 (1.1 to 1.7) | 2.1 (1.7 to 3.5) | 2.0 (1.6 to 3.7) | 3.5 (1.7 to 3.7) | 1.8 (1.6 to 2.0) | 1.9 (1.7 to 2.0) | 1.8 (1.6 to 3.5) | 1.8 (1.6 to 1.9) | 3.7 (1.7 to 5.3) |
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per Cheson 2014 for DLBCL. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 1: DLBCL 160 mg |
|---|---|
| Part 1: Progression-Free Survival (PFS) Per Cheson 2014 for DLBCL | 1.7 (1.4 to 2.2) |
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off |
|---|---|---|---|
| Part 2: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 2.0 (1.8 to 3.8) | 2.1 (1.7 to 3.7) | 1.9 (1.7 to 3.7) |
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off |
|---|---|---|---|
| Part 2: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 2.1 (1.8 to 3.8) | 2.2 (1.8 to 3.7) | 2.8 (1.7 to 9.0) |
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 3: TNBC 160 mg Cont |
|---|---|
| Part 3: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 1.6 (0.9 to 1.8) |
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
| months | Part 3: TNBC 160 mg Cont |
|---|---|
| Part 3: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 1.6 (0.9 to 1.8) |
OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan (SAP).
| percentage of participants | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: mCRPC 240 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: 2-year Overall Survival (OS) | 63.6 (35.5 to 82.1) | 42.1 (14.6 to 67.8) | 27.3 (8.9 to 49.8) | NA (NA to NA) | 36.1 (15.0 to 57.9) | 33.3 (15.0 to 52.9) | 15.3 (1.9 to 41.2) | 22.1 (9.4 to 38.2) | 14.3 (4.3 to 29.9) | 30.8 (16.0 to 46.9) | NA (NA to NA) | 23.1 (7.5 to 43.6) | 31.4 (10.8 to 54.7) |
OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan.
| percentage of participants | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off |
|---|---|---|---|
| Part 2: 2-year Overall Survival (OS) | 33.6 (15.5 to 52.9) | 22.7 (7.5 to 42.7) | 39.7 (20.3 to 58.6) |
OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan.
| percentage of participants | Part 3: TNBC 160 mg Cont |
|---|---|
| Part 3: 2-year Overall Survival (OS) | NA (NA to NA) |
The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
| CD8 percent marker area | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: mCRPC 240 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 10.93 ± 14.227 | 10.53 ± 12.456 | 0.70 ± 2.645 | -0.81 ± 0.537 | 0.96 ± 1.345 | 1.63 ± 2.372 | -0.42 ± 1.477 | 0.70 ± 1.141 | -0.01 ± 1.164 | 4.86 ± 3.751 | 0.16 ± 0.540 | 7.84 | 2.67 ± 4.156 |
The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
| CD8 percent marker area | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off |
|---|---|---|---|
| Part 2: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 3.81 ± 4.551 | -2.35 ± 5.586 | 1.23 ± 2.955 |
The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
| CD8 percent marker area | Part 3: TNBC 160 mg Cont |
|---|---|
| Part 3: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 0.26 |
Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.
| Participants | Part 1: RCC naïve 160 mg | Part 1: RCC naïve + Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve + Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve + Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AEs | 10 | 22 | 14 | 14 | 26 | 12 | 57 | 29 | 15 | 13 | 5 | 14 | 22 | 18 | 18 | 6 |
| Treatment-related AEs | 7 | 16 | 9 | 9 | 16 | 9 | 34 | 23 | 6 | 11 | 2 | 12 | 15 | 14 | 9 | 4 |
| SAEs | 3 | 7 | 9 | 7 | 15 | 5 | 28 | 11 | 3 | 6 | 0 | 4 | 11 | 7 | 7 | 3 |
| Treatment-related SAEs | 0 | 2 | 2 | 1 | 3 | 2 | 7 | 2 | 0 | 2 | 0 | 2 | 6 | 3 | 0 | 0 |
| Fatal SAEs | 1 | 0 | 1 | 0 | 2 | 1 | 3 | 1 | 0 | 1 | 0 | 0 | 1 | 2 | 0 | 0 |
| Treatment-related fatal SAEs | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of participants with at least one dose reduction of NIR178 and number of participants with at least one dose interruption of NIR178. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
| Participants | Part 1: RCC naïve 160 mg | Part 1: RCC naïve + Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve + Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve + Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| At least one dose reduction | 2 | 1 | 0 | 2 | 8 | 1 | 7 | 3 | 1 | 1 | 0 | 2 | 2 | 1 | 1 | 0 |
| At least one dose interruption | 6 | 9 | 2 | 8 | 12 | 3 | 20 | 9 | 3 | 3 | 1 | 5 | 8 | 5 | 4 | 0 |
Number of participants with at least one dose reduction of PDR001 and number of participants with at least one dose interruption of PDR001. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule. Dose reductions were not permitted for PDR001.
| Participants | Part 1: RCC naïve 160 mg | Part 1: RCC naïve + Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve + Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve + Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| At least one dose reduction | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| At least one dose interruption | 6 | 7 | 1 | 6 | 9 | 1 | 13 | 8 | 2 | 0 | 0 | 2 | 6 | 4 | 2 | 0 |
Dose intensity of NIR178 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days.
| mg/day | Part 1: RCC naïve 160 mg | Part 1: RCC naïve + Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve + Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve + Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1, 2 and 3: Dose Intensity of NIR178 | 316.7 (187 to 320) | 477.3 (321 to 480) | 320.0 (241 to 320) | 295.7 (140 to 320) | 309.8 (141 to 320) | 480.0 (272 to 480) | 320.0 (134 to 320) | 320.0 (179 to 320) | 320.0 (208 to 320) | 320.0 (233 to 320) | 480.0 (363 to 480) | 480.0 (382 to 496) | 320.0 (137 to 320) | 160.0 (96 to 173) | 160.0 (71 to 189) | 320.0 (319 to 320) |
Dose intensity of PDR001 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and then multiplied by 28 days.
| mg/28 days | Part 1: RCC naïve 160 mg | Part 1: RCC naïve + Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve + Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve + Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1, 2 and 3: Dose Intensity of PDR001 | 394.2 (300 to 400) | 396.2 (267 to 431) | 400.0 (395 to 400) | 393.1 (350 to 400) | 398.2 (319 to 402) | 400.0 (365 to 407) | 400.0 (236 to 405) | 400.0 (305 to 404) | 400.0 (389 to 406) | 400.0 (386 to 400) | 400.0 (400 to 400) | 400.0 (378 to 404) | 400.0 (224 to 406) | 400.0 (300 to 401) | 400.0 (387 to 410) | 400.0 (400 to 400) |
PDR001 immunogenicity was evaluated in serum samples. Patient anti-drug antibodies (ADA) status was defined as follows: * ADA-negative at baseline: ADA-negative sample at baseline * ADA-positive at baseline: ADA-positive sample at baseline * ADA-negative post-baseline: ADA-negative sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples * Treatment-reduced ADA-positive: ADA-positive sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples * Treatment-induced ADA-positive: ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample * Treatment-boosted ADA-positive: ADA-positive sample at baseline and at least 1 treatment-boosted ADA-positive sample * ADA-inconclusive: patient who does not qualify for any of the above definitions or a patient for which the baseline sample is missing
| Participants | Part 1: RCC naïve 160 mg | Part 1: RCC naïve + Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve + Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve + Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ADA-negative at baseline | 11 | 23 | 12 | 13 | 24 | 11 | 49 | 27 | 13 | 10 | 6 | 13 | 21 | 19 | 17 | 6 |
| ADA-positive at baseline | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| ADA-negative post-baseline | 10 | 23 | 11 | 12 | 22 | 11 | 48 | 25 | 13 | 10 | 6 | 11 | 21 | 14 | 14 | 5 |
| Treatment-reduced ADA-positive | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment-induced ADA-positive | 1 | 0 | 1 | 1 | 2 | 0 | 1 | 2 | 0 | 0 | 0 | 2 | 0 | 5 | 3 | 1 |
| Treatment-boosted ADA-positive | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| ADA-inconclusive | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first 28 days of treatment with NIR178 as single agent or in combination with PDR001 during the Japan safety run-in part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
| Participants | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont |
|---|---|---|---|
| Japan Safety Run-in: Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 | 0 | 0 |
Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.
| Participants | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont |
|---|---|---|---|
| AEs | 3 | 3 | 3 |
| Treatment-related AEs | 0 | 2 | 1 |
| SAEs | 2 | 1 | 1 |
| Treatment-related SAEs | 0 | 1 | 0 |
| Fatal SAEs | 0 | 0 | 0 |
| Treatment-related fatal SAEs | 0 | 0 | 0 |
Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
| ng/mL | NIR178 160 mg Capsule in Non-Japanese (Part 1 and 2) | NIR178 240 mg Capsule in Non-Japanese (Part 1) | NIR178 160 mg Tablet in Non-Japanese (Part 3) | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont |
|---|---|---|---|---|---|---|
| Cycle 1 Day 1 (all regimens) | 129 ± 335.0 | 160 ± 247.8 | 75.1 ± 382.3 | 81.8 ± 99.9 | 30.1 ± 32.9 | 234 ± 70.9 |
| Cycle 1 Day 7 (1 wk-on/1 wk-off) | 576 ± 83.1 | — | — | — | — | — |
| Cycle 1 Day 14 (2 wk-on/2 wk-off) | 392 ± 212.7 | — | — | — | — | — |
| Cycle 1 Day 28 (continuous) | 297 ± 291.4 | 622 ± 154.3 | 723 ± 295.5 | 311 ± 91.5 | 167 ± 40.9 | 3760 ± 39.6 |
Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
| hours | NIR178 160 mg Capsule in Non-Japanese (Part 1 and 2) | NIR178 240 mg Capsule in Non-Japanese (Part 1) | NIR178 160 mg Tablet in Non-Japanese (Part 3) | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont |
|---|---|---|---|---|---|---|
| Cycle 1 Day 1 (all regimens) | 2.00 (0.250 to 8.00) | 2.13 (0.50 to 8.00) | 1.50 (0.450 to 4.05) | 1.50 (1.47 to 1.50) | 1.50 (0.583 to 3.95) | 3.00 (2.03 to 3.03) |
| Cycle 1 Day 7 (1 wk-on/1 wk-off) | 1.45 (0.50 to 4.00) | — | — | — | — | — |
| Cycle 1 Day 14 (2 wk-on/2 wk-off) | 1.97 (0.550 to 7.67) | — | — | — | — | — |
| Cycle 1 Day 28 (continuous) | 2.00 (0.267 to 8.00) | 2.02 (0.250 to 7.60) | 1.52 (0.50 to 3.00) | 1.43 (0.50 to 1.48) | 1.45 (0.50 to 1.50) | 2.87 (1.92 to 4.00) |
PK parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.
| hr*ng/mL | NIR178 160 mg Capsule in Non-Japanese (Part 1 and 2) | NIR178 240 mg Capsule in Non-Japanese (Part 1) | NIR178 160 mg Tablet in Non-Japanese (Part 3) | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont |
|---|---|---|---|---|---|---|
| Cycle 1 Day 1 (all regimens) | 295 ± 198.3 | 487 ± 126.3 | 232 ± 437.4 | 170 ± 124.9 | 63.3 ± 88.0 | 550 |
| Cycle 1 Day 7 (1 wk-on/1 wk-off) | 1260 ± 63.2 | — | — | — | — | — |
| Cycle 1 Day 14 (2 wk-on/2 wk-off) | 1680 ± 94.4 | — | — | — | — | — |
| Cycle 1 Day 28 (continuous) | 918 ± 187.5 | 1620 ± 147.9 | 938 ± 412.2 | 697 ± 131.8 | 242 ± 13.5 | 12800 |
NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
| ng/mL | NIR178 160 mg Capsule in Non-Japanese (Part 1 and 2) | NIR178 240 mg Capsule in Non-Japanese (Part 1) | NIR178 160 mg Tablet in Non-Japanese (Part 3) | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont |
|---|---|---|---|---|---|---|
| Cycle 1 Day 1 (all regimens) | 25.5 ± 85.2 | 33.7 ± 64.2 | 20.1 ± 99.2 | — | 25.9 ± 77.0 | 28.5 ± 99.9 |
| Cycle 1 Day 7 (1 wk-on/1 wk-off) | 62.9 ± 39.4 | — | — | — | — | — |
| Cycle 1 Day 14 (2 wk-on/2 wk-off) | 71.3 ± 43.3 | — | — | — | — | — |
| Cycle 1 Day 28 (continuous) | 42.6 ± 82.2 | 77.3 ± 49.9 | 54.1 ± 102.4 | 45.6 ± 74.0 | 53.9 ± 64.2 | 111 ± 36.6 |
NJI765 is a NIR178 metabolite. Pharmacokinetic (PK) parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
| hours | NIR178 160 mg Capsule in Non-Japanese (Part 1 and 2) | NIR178 240 mg Capsule in Non-Japanese (Part 1) | NIR178 160 mg Tablet in Non-Japanese (Part 3) | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont |
|---|---|---|---|---|---|---|
| Cycle 1 Day 1 (all regimens) | 2.00 (0.250 to 8.05) | 2.08 (0.50 to 8.00) | 2.10 (0.450 to 4.05) | — | 1.95 (0.583 to 2.00) | 3.00 (2.03 to 3.03) |
| Cycle 1 Day 7 (1 wk-on/1 wk-off) | 1.50 (0.50 to 4.00) | — | — | — | — | — |
| Cycle 1 Day 14 (2 wk-on/2 wk-off) | 1.98 (0.550 to 3.00) | — | — | — | — | — |
| Cycle 1 Day 28 (continuous) | 2.00 (0.483 to 8.03) | 2.10 (0.250 to 7.88) | 0.750 (0.50 to 2.03) | 2.23 (1.43 to 3.02) | 1.45 (0.50 to 1.50) | 2.87 (1.92 to 4.00) |
NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.
| hr*ng/mL | NIR178 160 mg Capsule in Non-Japanese (Part 1 and 2) | NIR178 240 mg Capsule in Non-Japanese (Part 1) | NIR178 160 mg Tablet in Non-Japanese (Part 3) | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont |
|---|---|---|---|---|---|---|
| Cycle 1 Day 1 (all regimens) | 98.2 ± 87.1 | 122 ± 75.6 | 77.1 ± 35.9 | — | 117 ± 68.2 | 119 |
| Cycle 1 Day 7 (1 wk-on/1 wk-off) | 243 ± 57.5 | — | — | — | — | — |
| Cycle 1 Day 14 (2 wk-on/2 wk-off) | 288 ± 23.7 | — | — | — | — | — |
| Cycle 1 Day 28 (continuous) | 214 ± 76.6 | 382 ± 43.7 | 226 ± 147.0 | — | 277 ± 69.0 | 362 |
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
| µg/mL | Non-Japanese Patients | Japanese Patients |
|---|---|---|
| First dose (Cycle 1 Day 1 or Cycle 2 Day 1) | 93.2 ± 30.8 | 85.0 ± 12.8 |
| Cycle 3 Day 1 | 126 ± 37.4 | 119 |
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
| hours | Non-Japanese Patients | Japanese Patients |
|---|---|---|
| First dose (Cycle 1 Day 1 or Cycle 2 Day 1) | 1.50 (0.333 to 718) | 1.50 (1.48 to 1.52) |
| Cycle 3 Day 1 | 1.50 (0.550 to 358) | 1.65 (1.65 to 1.65) |
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-28day calculation.
| day*µg/mL | Non-Japanese Patients | Japanese Patients |
|---|---|---|
| First dose (Cycle 1 Day 1 or Cycle 2 Day 1) | 1140 ± 31.2 | 1110 ± 13.9 |
| Cycle 3 Day 1 | 2030 ± 41.3 | — |
On-treatment and post-treatment safety follow-up deaths were collected from first dose of study medication to 150 days after last dose of NIR178+PDR001. Survival follow-up deaths were collected from 151 days after last dose of NIR178+PDR001 until end of study. All deaths refer to the sum of on-treatment and post-treatment safety follow-up deaths plus survival follow-up deaths.
| participants | Part 1: RCC naïve 160 mg | Part 1: RCC naïve + Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve + Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve + Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| On-treatment and post-treatment safety follow-up deaths | 4 | 6 | 10 | 6 | 8 | 4 | 22 | 9 | 7 | 9 | 2 | 2 | 6 | 4 | 6 | 4 | 2 | 0 | 1 |
| Survival follow-up deaths | 3 | 7 | 3 | 4 | 12 | 4 | 22 | 12 | 8 | 2 | 3 | 7 | 8 | 9 | 7 | 1 | — | — | 1 |
| All deaths | 7 | 13 | 13 | 10 | 20 | 8 | 44 | 21 | 15 | 11 | 5 | 9 | 14 | 13 | 13 | 5 | 2 | 0 | 2 |
Collected over On-treatment and post-treatment safety follow-up: from first dose of study treatment to 150 days after last dose of NIR178+PDR001, up to 4.3 years (Part 1), 5.1 years (Part 2), 0.9 years (Part 3) and 0.9 years (Japan safety run-in; JSR). Deaths in survival period: from 151 days after last dose of NIR178+PDR001 until end of study, up to 4.3 years (Part 1), 5.1 years (Part 2), 0.9 years (Part 3) and 0.9 years (JSR).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | 4/11 (36.4%) | 3/11 (27.3%) | 10/11 (90.9%) |
| Part 1: RCC naïve + Pre 240 mg | 6/23 (26.1%) | 7/23 (30.4%) | 22/23 (95.7%) |
| Part 1: Pancreatic 160 mg | 10/14 (71.4%) | 9/14 (64.3%) | 14/14 (100%) |
| Part 1: Urothelial 160 mg | 6/14 (42.9%) | 7/14 (50%) | 14/14 (100%) |
| Part 1: H-N naïve + Pre 160 mg | 8/26 (30.8%) | 16/26 (61.5%) | 25/26 (96.2%) |
| Part 1: H-N Pre 240 mg | 4/12 (33.3%) | 5/12 (41.7%) | 12/12 (100%) |
| Part 1: MSS CRC 160 mg | 22/58 (37.9%) | 28/58 (48.3%) | 52/58 (89.7%) |
| Part 1: TNBC 160 mg | 9/30 (30%) | 14/30 (46.7%) | 29/30 (96.7%) |
| Part 1: Melanoma naïve + Pre 160 mg | 7/16 (43.8%) | 4/16 (25%) | 14/16 (87.5%) |
| Part 1: DLBCL 160 mg | 9/13 (69.2%) | 7/13 (53.8%) | 13/13 (100%) |
| Part 1: DLBCL 240 mg | 2/6 (33.3%) | 0/6 (0%) | 5/6 (83.3%) |
| Part 1: mCRPC 240 mg | 2/15 (13.3%) | 5/15 (33.3%) | 14/15 (93.3%) |
| Part 2: NSCLC 160 mg Cont | 6/22 (27.3%) | 11/22 (50%) | 22/22 (100%) |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | 4/20 (20%) | 9/20 (45%) | 16/20 (80%) |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | 6/20 (30%) | 7/20 (35%) | 17/20 (85%) |
| Part 3: TNBC 160 mg Cont | 4/6 (66.7%) | 3/6 (50%) | 6/6 (100%) |
| JSR: 80 mg Cont | 2/3 (66.7%) | 2/3 (66.7%) | 3/3 (100%) |
| JSR: 160 mg Cont | 0/3 (0%) | 1/3 (33.3%) | 2/3 (66.7%) |
| JSR: 240 mg Cont | 1/3 (33.3%) | 1/3 (33.3%) | 3/3 (100%) |
| Part 1: RCC naïve 160 mg_Survival Period | 3/7 (42.9%) | — | — |
| Part 1: RCC naïve + Pre 240 mg_Survival Period | 7/17 (41.2%) | — | — |
| Part 1: Pancreatic 160 mg_Survival Period | 3/4 (75%) | — | — |
| Part 1: Urothelial 160 mg_Survival Period | 4/8 (50%) | — | — |
| Part 1: H-N naïve + Pre 160 mg_Survival Period | 12/18 (66.7%) | — | — |
| Part 1: H-N Pre 240 mg_Survival Period | 4/8 (50%) | — | — |
| Part 1: MSS CRC 160 mg_Survival Period | 22/36 (61.1%) | — | — |
| Part 1: TNBC 160 mg_Survival Period | 12/21 (57.1%) | — | — |
| Part 1: Melanoma naïve + Pre 160 mg_Survival Period | 8/9 (88.9%) | — | — |
| Part 1: DLBCL 160 mg_Survival Period | 2/4 (50%) | — | — |
| Part 1: DLBCL 240 mg_Survival Period | 3/4 (75%) | — | — |
| Part 1: mCRPC 240 mg_Survival Period | 7/13 (53.8%) | — | — |
| Part 2: NSCLC 160 mg cont_Survival Period | 8/16 (50%) | — | — |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off_Survival Period | 9/16 (56.3%) | — | — |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off_Survival Period | 7/14 (50%) | — | — |
| Part 3: TNBC 160 mg cont_Survival Period | 1/2 (50%) | — | — |
| JSR: 80 mg cont_Survival Period | — | — | — |
| JSR: 160 mg cont_Survival Period | — | — | — |
| JSR: 240 mg cont_Survival Period | 1/1 (100%) | — | — |
| Event | Part 1: RCC naïve 160 mg | Part 1: RCC naïve + Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve + Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve + Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont | Part 1: RCC naïve 160 mg_Survival Period | Part 1: RCC naïve + Pre 240 mg_Survival Period | Part 1: Pancreatic 160 mg_Survival Period | Part 1: Urothelial 160 mg_Survival Period | Part 1: H-N naïve + Pre 160 mg_Survival Period | Part 1: H-N Pre 240 mg_Survival Period | Part 1: MSS CRC 160 mg_Survival Period | Part 1: TNBC 160 mg_Survival Period | Part 1: Melanoma naïve + Pre 160 mg_Survival Period | Part 1: DLBCL 160 mg_Survival Period | Part 1: DLBCL 240 mg_Survival Period | Part 1: mCRPC 240 mg_Survival Period | Part 2: NSCLC 160 mg cont_Survival Period | Part 2: NSCLC 160 mg 2wk-on/2wk-off_Survival Period | Part 2: NSCLC 160 mg 1wk-on/1wk-off_Survival Period | Part 3: TNBC 160 mg cont_Survival Period | JSR: 80 mg cont_Survival Period | JSR: 160 mg cont_Survival Period | JSR: 240 mg cont_Survival Period |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pericardial effusionCardiac disorders | 0/11 | 0/23 | 0/14 | 0/14 | 0/26 | 0/12 | 0/58 | 0/30 | 0/16 | 0/13 | 0/6 | 0/15 | 0/22 | 1/20 | 2/20 | 0/6 | 1/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| NauseaGastrointestinal disorders | 0/11 | 0/23 | 0/14 | 0/14 | 0/26 | 0/12 | 0/58 | 0/30 | 0/16 | 0/13 | 0/6 | 0/15 | 0/22 | 1/20 | 0/20 | 0/6 | 0/3 | 0/3 | 1/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| VomitingGastrointestinal disorders | 0/11 | 0/23 | 0/14 | 0/14 | 0/26 | 0/12 | 1/58 | 0/30 | 0/16 | 1/13 | 0/6 | 0/15 | 1/22 | 0/20 | 0/20 | 0/6 | 0/3 | 0/3 | 1/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| Immune-mediated hepatitisHepatobiliary disorders | 0/11 | 0/23 | 0/14 | 0/14 | 0/26 | 0/12 | 0/58 | 0/30 | 0/16 | 0/13 | 0/6 | 0/15 | 0/22 | 0/20 | 0/20 | 0/6 | 0/3 | 1/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| CoughRespiratory, thoracic and mediastinal disorders | 0/11 | 0/23 | 0/14 | 0/14 | 0/26 | 0/12 | 0/58 | 0/30 | 0/16 | 0/13 | 0/6 | 0/15 | 0/22 | 0/20 | 0/20 | 0/6 | 1/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| Pulmonary haemorrhageRespiratory, thoracic and mediastinal disorders | 0/11 | 0/23 | 0/14 | 0/14 | 1/26 | 0/12 | 0/58 | 0/30 | 0/16 | 0/13 | 0/6 | 0/15 | 0/22 | 1/20 | 0/20 | 0/6 | 1/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| General physical health deteriorationGeneral disorders | 1/11 | 0/23 | 2/14 | 0/14 | 2/26 | 0/12 | 1/58 | 0/30 | 1/16 | 2/13 | 0/6 | 0/15 | 0/22 | 1/20 | 0/20 | 1/6 | 0/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 0/11 | 0/23 | 0/14 | 1/14 | 0/26 | 0/12 | 0/58 | 1/30 | 0/16 | 0/13 | 0/6 | 0/15 | 1/22 | 0/20 | 3/20 | 1/6 | 0/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| Aortic aneurysmVascular disorders | 0/11 | 0/23 | 0/14 | 0/14 | 0/26 | 0/12 | 0/58 | 0/30 | 0/16 | 0/13 | 0/6 | 0/15 | 0/22 | 0/20 | 1/20 | 1/6 | 0/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| SepsisInfections and infestations | 0/11 | 1/23 | 1/14 | 2/14 | 0/26 | 0/12 | 0/58 | 0/30 | 0/16 | 1/13 | 0/6 | 0/15 | 0/22 | 0/20 | 0/20 | 0/6 | 0/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| Event | Part 1: RCC naïve 160 mg | Part 1: RCC naïve + Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve + Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve + Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont | Part 1: RCC naïve 160 mg_Survival Period | Part 1: RCC naïve + Pre 240 mg_Survival Period | Part 1: Pancreatic 160 mg_Survival Period | Part 1: Urothelial 160 mg_Survival Period | Part 1: H-N naïve + Pre 160 mg_Survival Period | Part 1: H-N Pre 240 mg_Survival Period | Part 1: MSS CRC 160 mg_Survival Period | Part 1: TNBC 160 mg_Survival Period | Part 1: Melanoma naïve + Pre 160 mg_Survival Period | Part 1: DLBCL 160 mg_Survival Period | Part 1: DLBCL 240 mg_Survival Period | Part 1: mCRPC 240 mg_Survival Period | Part 2: NSCLC 160 mg cont_Survival Period | Part 2: NSCLC 160 mg 2wk-on/2wk-off_Survival Period | Part 2: NSCLC 160 mg 1wk-on/1wk-off_Survival Period | Part 3: TNBC 160 mg cont_Survival Period | JSR: 80 mg cont_Survival Period | JSR: 160 mg cont_Survival Period | JSR: 240 mg cont_Survival Period |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NauseaGastrointestinal disorders | 1/11 | 5/23 | 4/14 | 5/14 | 6/26 | 2/12 | 13/58 | 9/30 | 4/16 | 2/13 | 0/6 | 5/15 | 5/22 | 3/20 | 3/20 | 4/6 | 1/3 | 0/3 | 1/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| Lymphocyte count decreasedInvestigations | 0/11 | 0/23 | 0/14 | 0/14 | 0/26 | 0/12 | 1/58 | 0/30 | 0/16 | 0/13 | 0/6 | 0/15 | 1/22 | 0/20 | 0/20 | 0/6 | 2/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| Decreased appetiteMetabolism and nutrition disorders | 1/11 | 3/23 | 7/14 | 5/14 | 6/26 | 0/12 | 17/58 | 4/30 | 2/16 | 3/13 | 0/6 | 2/15 | 6/22 | 5/20 | 3/20 | 1/6 | 0/3 | 0/3 | 2/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| DiarrhoeaGastrointestinal disorders | 1/11 | 8/23 | 0/14 | 4/14 | 4/26 | 1/12 | 12/58 | 3/30 | 0/16 | 1/13 | 0/6 | 3/15 | 4/22 | 1/20 | 2/20 | 3/6 | 0/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| FatigueGeneral disorders | 4/11 | 5/23 | 5/14 | 2/14 | 11/26 | 3/12 | 20/58 | 10/30 | 3/16 | 1/13 | 0/6 | 4/15 | 11/22 | 6/20 | 5/20 | 3/6 | 1/3 | 0/3 | 1/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| ConstipationGastrointestinal disorders | 1/11 | 7/23 | 1/14 | 2/14 | 4/26 | 1/12 | 9/58 | 2/30 | 1/16 | 3/13 | 1/6 | 2/15 | 8/22 | 3/20 | 8/20 | 2/6 | 0/3 | 1/3 | 1/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| AnaemiaBlood and lymphatic system disorders | 0/11 | 2/23 | 3/14 | 5/14 | 5/26 | 0/12 | 5/58 | 4/30 | 3/16 | 3/13 | 1/6 | 2/15 | 1/22 | 3/20 | 3/20 | 0/6 | 0/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| DizzinessNervous system disorders | 0/11 | 2/23 | 5/14 | 2/14 | 1/26 | 1/12 | 1/58 | 4/30 | 0/16 | 1/13 | 0/6 | 1/15 | 2/22 | 1/20 | 1/20 | 1/6 | 0/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| Abdominal painGastrointestinal disorders | 1/11 | 2/23 | 4/14 | 1/14 | 3/26 | 0/12 | 9/58 | 2/30 | 1/16 | 0/13 | 0/6 | 2/15 | 0/22 | 1/20 | 0/20 | 2/6 | 0/3 | 0/3 | 0/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| Gastrointestinal disorderGastrointestinal disorders | 0/11 | 0/23 | 0/14 | 0/14 | 0/26 | 0/12 | 0/58 | 0/30 | 0/16 | 0/13 | 0/6 | 0/15 | 0/22 | 0/20 | 0/20 | 0/6 | 0/3 | 0/3 | 1/3 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| Age, Continuous(years) | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: MSS CRC Unk 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 65.5 ± 10.86 | 60.0 ± 11.96 | 60.6 ± 8.54 | 60.4 ± 8.98 | 66.9 ± 9.63 | 61.6 ± 7.13 | 59.4 ± 9.05 | 60.2 ± 7.07 | 56.5 ± 9.04 | 58.1 ± 11.21 | 46.0 ± 15.56 | 49.8 ± 10.81 | 50.3 ± 20.65 | 54.2 ± 14.87 | 55.0 ± 18.65 | 61.5 ± 13.10 | 68.3 ± 8.14 | 65.0 ± 9.02 | 61.8 ± 9.51 | 64.2 ± 8.94 | 58.5 ± 16.16 | 61.3 ± 10.69 | 57.0 ± 9.54 | 44.3 ± 8.33 | 59.5 ± 11.59 |
| Sex: Female, Male(Participants) | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: MSS CRC Unk 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | 3 | 0 | 2 | 6 | 5 | 2 | 3 | 3 | 9 | 8 | 1 | 30 | 1 | 3 | 7 | 3 | 0 | 7 | 7 | 8 | 6 | 3 | 1 | 1 | 119 |
| Male | 8 | 12 | 9 | 8 | 9 | 13 | 8 | 9 | 18 | 21 | 1 | 0 | 2 | 10 | 6 | 3 | 15 | 15 | 13 | 12 | 0 | 0 | 2 | 2 | 196 |
| Race/Ethnicity, Customized(Participants) | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: MSS CRC Unk 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| White | 9 | 3 | 10 | 13 | 5 | 14 | 9 | 12 | 20 | 23 | 2 | 21 | 1 | 13 | 7 | 0 | 13 | 10 | 7 | 7 | 1 | 0 | 0 | 0 | 200 |
| Black or African American | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 3 | 10 |
| Asian | 2 | 8 | 0 | 0 | 8 | 1 | 0 | 0 | 6 | 1 | 0 | 2 | 2 | 0 | 4 | 6 | 2 | 11 | 13 | 12 | 0 | 0 | 0 | 0 | 78 |
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 3 | 0 | 0 | 0 | 5 |
| Unknown | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 5 | 0 | 7 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 21 |
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