A Phase 1/2 interventional study of Amcenestrant and Palbociclib in Breast Cancer, sponsored by Sanofi. Terminated at 25 sites in 10 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-24.
Sponsored by Sanofi · Phase 1/2, Interventional, and Treatment
Primary Objectives:
Dose Escalation:
Safety Run-In:
- To confirm the RD of amcenestrant in combination with alpelisib
Dose Expansion:
Secondary Objectives:
Duration of the study, per participant, will include eligibility period (screening period) of up to 4 weeks (28 days), treatment period (at least 1 cycle [28 days] of study treatment), and end of treatment (EOT) visit at least 22 to 30 days (or until the participant receives another anticancer therapy, whichever is earlier) following the last study treatment administration. The expected enrollment period is approximately 60 months.
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's enrollment of 136 is above the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Sanofi is the lead sponsor of 1,557 studies on the registry; 91 are open to participants now.
Of its 205 completed or terminated interventional studies of FDA-regulated products, 123 (60%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Arm #3 - Part F and Arm #5 - Part J: up to 2 prior lines of either single endocrine therapy and/or endocrine-based therapy Arm #4 -H: up to 2 prior lines of either single endocrine therapy and/or endocrine-based therapy (exemestane not allowed)
- Dose Expansion study parts: Arm #2: - Part D: no more than 2 prior lines of advanced endocrine therapy for advanced disease are allowed Arm #3, - Part G: patients must have received and progressed on the combination of Aromatase Inhibitors (AI) + CDK4/6 inhibitor as the (1L) treatment for advanced disease Arm #4 - Part I: participants must have received and progressed on the combination of Aromatase Inhibitors (AI) +CDK4/6 Inhibitor as the first line (1L) treatment for advanced disease (exemestane not allowed) Arm#5: - Part K: up to 1 prior line of a single endocrine therapy for advanced disease Note: Additional patients who while on previous endocrine therapy that was initiated ≥24 months ago, or relapsed \< 12 months after completion of adjuvant endocrine therapy are also allowed for Arms #2, #3, #4, and #5 (Parts C, D, F, G, H, I, J and K).
Exclusion criteria:
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
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.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
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.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
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.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Part A: Amcenestrant will be administered orally once daily (QD). Treatment will begin with an identified starting dose. Administration of higher doses to subsequent participants is based on occurrence of DLTs and evaluation of target saturation and PK parameters at initial and subsequent doses, until maximum administered dose (MAD) is reached. Drug will be administered in a 28-day cycle. Part B: When the dose escalation phase ends, the recommended dose will be administered for the expansion cohort. Drug will be administered in a 28-day cycle.
Drug: Amcenestrant
Part C: Amcenestrant will be administered in combination with palbociclib: amcenestrant starting oral daily dose will be one dose level below monotherapy RD and palbociclib will be dosed at fixed standard dose. Administration of higher dose of amcenestrant (with standard palbociclib dose) to subsequent participants will be based on occurrence of DLTs at initial and subsequent doses, until MAD of amcenestrant is reached. Drugs will be administered in a 28-day cycle (palbociclib will be administered for 21 days of cycle). Part D: Based on the results in Part C, participants will be administered either: 1) a determined amcenestrant dose (RD) with standard dose of palbociclib in combination therapy, or 2) one of two randomized dose levels of amcenestrant with standard dose of palbociclib in combination therapy. Drugs will be administered in a 28-day cycle (palbociclib will be administered for 21 days of cycle).
Drug: Amcenestrant · Drug: Palbociclib
Part F: Amcenestrant will be administered in combination with alpelisib at a fixed standard dose. Additional dose levels of amcenestrant with alpelisib could be explored if needed based on the safety and PK results. Lower dose of alpelisib could be explored based on the PK results and safety profile from the initial combination administration. Both amcenestrant and alpelisib will be administered in a 28-day cycle. Part G: Based on the conclusion in Part F, participants will be administered the determined RD of amcenestrant and alpelisib given in the combination in an expansion cohort. Both study drugs will be administered in a 28-day cycle.
Drug: Amcenestrant · Drug: Alpelisib
Part H: Amcenestrant will be administered at the determined RD in combination with 2 dose levels of everolimus. Additional dose levels of amcenestrant with everolimus could be explored if needed based on the safety and PK results. Both amcenestrant and everolimus will be administered in a 28-day cycle. Part I: Based on the conclusion in Part H, participants will be administered the determined RD of amcenestrant and RD of everolimus given in the combination in an expansion cohort. Both study drugs will be administered in a 28-day cycle.
Drug: Amcenestrant · Drug: Everolimus
Part J: Amcenestrant will be administered at the determined RD in combination with 2 dose levels of abemaciclib. Additional dose levels of amcenestrant with abemaciclib could be explored if needed based on the safety and PK results. Both amcenestrant and abemaciclib will be administered in a 28-day cycle. Part K: Based on the conclusion in Part J, participants will be administered the determined RD of amcenestrant and RD of abemaciclib given in the combination in an expansion cohort. Both study drugs will be administered in a 28-day cycle.
Drug: Amcenestrant · Drug: Abemaciclib
Pharmaceutical form: capsule Route of administration: oral
Also known as: SAR439859
Pharmaceutical form: capsule Route of administration: oral
Also known as: Ibrance®
Pharmaceutical form: tablet Route of administration: oral
Also known as: Piqray®
Pharmaceutical form: tablet
Pharmaceutical form: tablet
Also known as: Verzenio®
Parts A, C, F, H, J: Number of Participants With Study Treatment-Related Dose-Limiting Toxicities (DLTs)
DLTs: any treatment-emergent adverse event(TEAE) related to study treatment per National Cancer Institute Common Terminology Criteria for AE scale version (v) 4.03:Grade(G)≥3 nonhematological toxicity except:G3 nausea/vomiting resolved to G≤1 in 48 hours(h),G3 diarrhea with therapy and lasting\<48h,G3 hyperglycemia resolved to G≤1 in 48h(Part H);G≥3 hematological toxicity except:G3 anemia,G4 neutropenia\<7days(d),G3 neutropenia without fever/infection,G3 thrombocytopenia without bleeding;elevated total serum bilirubin(BL)\>2xupper limit of normal(except Part F),Part F:G3 hyperglycemia not resolved to G≤2 in 7d after antidiabetic treatment,G2 hyperglycemia not resolved to G≤1 in 21d,G2 alanine aminotransferase(ALT) increase in conjunction with total blood BL G≥2 without liver metastases,G≥3 ALT/aspartate aminotransferase increase for\>4d,G3 rash/maculopapular rash not resolved to G≤1 in 7d;treatment related toxicity causing≥7d omission in Cycle 1 or \>2 weeks delay in Cycle 2 in Part C.
Time frame: Cycle 1 Day 1 to Cycle 1 Day 28 (cycle duration=28 days)
Part B: Objective Response Rate (ORR) as Determined by Independent Central Review (ICR)
ORR was determined by dividing the number of participants who achieved confirmed complete response (CR) or partial response (PR) by the number of participants from the analysis population. ORR was assessed by ICR according to response evaluation criteria in solid tumors (RECIST) v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 278 weeks
Parts D, I: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs)
AE was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which did not necessarily had a causal relationship with the treatment. SAE was any untoward medical occurrence that at any dose, resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed or worsened or became serious during the treatment period.
Time frame: From first dose of study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration; approximately 232 weeks for Part D and 11 weeks for Part I
Parts A, B, C, F, H, J: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events
AE was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which did not necessarily had a causal relationship with the treatment. SAE was any untoward medical occurrence that at any dose, resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed or worsened or became serious during the treatment period.
Time frame: From first dose of study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration; approximately 94, 282, 144, 96, 59, 130 weeks for Parts A, B, C, F, H, J respectively
Parts A, B, C, D, F, H, I, J: Objective Response Rate as Determined by Investigators/Local Radiologists
ORR was determined by dividing the number of participants who achieved confirmed CR or PR by the number of participants from the analysis population. ORR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228, 92, 55, 7, 126 weeks for Parts A, B, C, D, F, H, I, J respectively
Parts A, B, C, D, F, H, I, J: Clinical Benefit Rate (CBR) as Determined by Investigators/Local Radiologists
CBR was determined by dividing the number of participants who achieved confirmed CR, PR as best overall response (BOR) or stable disease (SD) for ≥24 weeks by the number of participants from the analysis population. CBR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228, 92, 55, 7, 126 weeks for Parts A, B, C, D, F, H, I, J respectively
Part B: Clinical Benefit Rate as Determined by Independent Central Review
CBR was determined by dividing the number of participants who achieved confirmed CR, PR as BOR or SD for ≥24 weeks by the number of participants from the analysis population. CBR was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 278 weeks
Parts A, B, C, D, F, H, I, J: Duration of Response (DOR) as Determined by Investigators/Local Radiologists
DOR was defined as the time interval from the date of the first occurrence of confirmed CR or PR to the date of the first documentation of disease progression or death due to disease progression, whichever occurred first. DOR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, an absolute increase of at least 5 mm in the sum. Appearance of 1 or more new lesions was also considered progression.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228, 92, 55, 7, 126 weeks for Parts A, B, C, D, F, H, I, J respectively
Part B: Duration of Response as Determined by Independent Central Review
DOR was defined as the time interval from the date of the first occurrence of confirmed CR or PR to the date of the first documentation of disease progression or death due to disease progression, whichever occurred first. DOR was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, an absolute increase of at least 5 mm in the sum. Appearance of 1 or more new lesions was also considered progression.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 278 weeks
Parts A, B, C, D, F, H, I, J: Progression-Free Survival (PFS) as Determined by Investigators/Local Radiologists
PFS was defined as time from the date of the first treatment intake to the date of the first documentation of objective PD according to RECIST v1.1, clinical PD or death due to any cause, whichever occurred first. PFS was assessed by investigators/local radiologists. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, an absolute increase of at least 5 mm in the sum. Appearance of 1 or more new lesions was also considered progression.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228, 92, 55, 7, 126 weeks for Parts A, B, C, D, F, H, I, J respectively
Parts A, B, C, D: Objective Response Rate as Determined by Investigators/Local Radiologists According to Estrogen Receptor 1 (ESR1) Mutation at Baseline
ORR was determined by dividing the number of participants who achieved confirmed CR or PR by the number of participants from the analysis population. ORR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The ESR1 gene mutation status (mutated or wild-type) was analyzed by multiplex droplet digital polymerase chain reaction (ddPCR) after extraction of plasma circulating deoxyribonucleic acid (DNA). The baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.
Time frame: From Baseline (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228 weeks for Parts A, B, C, D respectively
Part B: Objective Response Rate as Determined by Independent Central Review According to Estrogen Receptor 1 Mutation at Baseline
ORR was determined by dividing the number of participants who achieved confirmed CR or PR by the number of participants from the analysis population. ORR was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The ESR1 gene mutation status (mutated or wild-type) was analyzed by multiplex ddPCR after extraction of plasma circulating DNA. The baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.
Time frame: Baseline (Day 1) up to maximum exposure of study treatment; approximately 278 weeks
Parts A, B, C, D: Clinical Benefit Rate as Determined by Investigators/Local Radiologists According to Estrogen Receptor 1 Mutation at Baseline
CBR was determined by dividing the number of participants who achieved confirmed CR, PR as BOR or SD for ≥24 weeks by the number of participants from analysis population. CBR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The ESR1 gene mutation status (mutated or wild-type) was analyzed by multiplex ddPCR after extraction of plasma circulating DNA. Baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.
Time frame: From Baseline (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228 weeks for Parts A, B, C, D respectively
Parts B, D, I: Time to First Confirmed Response as Determined by Investigators/Local Radiologists
The time to first confirmed response was defined as the time interval from the date of first administration of the study treatment to the date of the first occurrence of confirmed CR or PR. The time to first confirmed response was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228, 92, 55, 7, 126 weeks for Parts A, B, C, D, F, H, I, J respectively
Part B: Time to First Confirmed Response as Determined by Independent Central Review
The time to first confirmed response was defined as the time interval from the date of first administration of the study treatment to the date of the first occurrence of confirmed CR or PR. The time to first confirmed response was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 278 weeks
Part A: Number of Participants With 18F-Fluorestradiol Positron Emission Tomography Percentage Reduction
Inhibition of estrogen receptor (ER) occupancy investigation using 18F-FES-PET imaging was a limited invasive procedure that allowed assessment of ER presence by assessing the binding of radiolabeled estradiol, the ligand of ER (signal extinction). Number of participants with percentage reduction (≥90%, ≥70%, ≥50% and ≥30%) in 18F-FES-PET signal are reported. The baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.
Time frame: Baseline (within 3 days or more prior to Day 1) and between Day 11 and Day 15 of Cycle 1 (cycle duration=28 days)
Parts A, B, C, D, H, I, J: Time Interval Between Administration and the Sampling Preceding the First Concentration Above the Lower Limit of Quantification (LLOQ) (Tlag) of Amcenestrant After a Single Oral Administration
Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. Pharmacokinetic (PK) parameters were determined by non-compartmental analysis. LLOQ value for amcenestrant was 5 nanograms per milliliter (ng/mL).
Time frame: Cycle 1 Day 1 (cycle duration=28 days)
Parts A, B, C, D, H, I, J: Time to Reach Maximum Plasma Concentration (Tmax) of Amcenestrant After a Single Oral Administration
Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.
Time frame: Cycle 1 Day 1 (cycle duration=28 days)
Parts A, B, C, D, H, I, J: Maximum Plasma Concentration (Cmax) of Amcenestrant After a Single Oral Administration
Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.
Time frame: Cycle 1 Day 1 (cycle duration=28 days)
Parts A, B, C, D, H, I, J: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Dosing Interval (AUC0-tau) of Amcenestrant After a Single Oral Administration
Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis. tau=12 h for Part A BID dosing and 24 h for other parts.
Time frame: Cycle 1 Day 1 (cycle duration=28 days)
Parts A, B, C, D, F, H, I, J: Time to Reach Maximum Plasma Concentration of Amcenestrant After Repeated Oral Administrations
Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.
Time frame: Parts A, B, F, H, I, J: Cycle 1 Day 22; Parts C and D: Cycle 1 Day 21 (cycle duration=28 days)
Parts A, B, C, D, F, H, I, J: Maximum Plasma Concentration of Amcenestrant After Repeated Oral Administrations
Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.
Time frame: Parts A, B, F, H, I, J: Cycle 1 Day 22; Parts C and D: Cycle 1 Day 21 (cycle duration=28 days)
Parts A, B, C, D, F, H, I, J: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Dosing Interval of Amcenestrant After Repeated Oral Administrations
Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis. tau=12 h for Part A BID dosing and 24 h for other parts.
Time frame: Parts A, B, F, H, I, J: Cycle 1 Day 22; Parts C and D: Cycle 1 Day 21 (cycle duration=28 days)
Parts A, B, C, D, F, H, I, J: Plasma Concentration Observed Before Treatment Administration (Ctrough) of Amcenestrant
Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations.
Time frame: Cycle 1: Pre-dose (0 hour) on Day 8 (Parts A, B, C, D), Day 15 (Parts B, C, D), Day 21 (Parts C and D) and Day 22 (Parts A, B, F, H, I, J) (cycle duration=28 days)
Part B: Cumulated Amount of Amcenestrant Excreted in Urine From Time 0 to 24 Hours (Ae0-24)
Urine samples were collected at the specified timepoints for the measurement of amcenestrant amount excreted in urine.
Time frame: Day 22 of Cycle 1 (cycle duration=28 days)
Part A (QD Regimen): Geometric Mean Ratio of Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24) of Amcenestrant
The food effect was assessed by comparing the geometric means of AUC0-24 between Cycle 1 Day 1 (fasted condition) and Cycle 1 Day 3 (fed condition) in Part A.
Time frame: Days 1 and 3 of Cycle 1 (cycle duration=28 days)
Part A (QD Regimen): Geometric Mean Ratio of Maximum Plasma Concentration of Amcenestrant
The food effect was assessed by comparing the geometric means of Cmax between Cycle 1 Day 1 (fasted condition) and Cycle 1 Day 3 (fed condition) in Part A.
Time frame: Days 1 and 3 of Cycle 1 (cycle duration=28 days)
Parts C and D: Time to Reach Maximum Plasma Concentration of Palbociclib After First Dose and Repeated Oral Administrations in Combination With Amcenestrant
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 21) of palbociclib in combination with amcenestrant for the measurement of palbociclib concentrations. PK parameters were determined by non-compartmental analysis.
Time frame: Days 1 and 21 of Cycle 1 (cycle duration=28 days)
Parts C and D: Maximum Plasma Concentration of Palbociclib After First Dose and Repeated Oral Administrations in Combination With Amcenestrant
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 21) of palbociclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
Time frame: Days 1 and 21 of Cycle 1 (cycle duration=28 days)
Parts C and D: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours of Palbociclib After First Dose and Repeated Oral Administrations in Combination With Amcenestrant
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 21) of palbociclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
Time frame: Days 1 and 21 of Cycle 1 (cycle duration=28 days)
Part F: Time to Reach Maximum Plasma Concentration of Alpelisib After Repeated Oral Administrations Alone or in Combination With Amcenestrant
Blood samples were collected after 3-day repeated oral administrations of alpelisib as monotherapy (Day 3) and after 22-day repeated oral administrations of alpelisib in combination with repeated doses of amcenestrant (Day 22). PK parameters were determined by non-compartmental analysis.
Time frame: Days 3 and 22 of Cycle 1 (cycle duration=28 days)
Part F: Maximum Plasma Concentration of Alpelisib After Repeated Oral Administrations Alone or in Combination With Amcenestrant
Blood samples were collected after 3-day repeated oral administrations of alpelisib as monotherapy (Day 3) and after 22-day repeated oral administrations of alpelisib in combination with repeated doses of amcenestrant (Day 22). PK parameters were determined by non-compartmental analysis.
Time frame: Days 3 and 22 of Cycle 1 (cycle duration=28 days)
Part F: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours of Alpelisib After Repeated Oral Administrations Alone or in Combination With Amcenestrant
Blood samples were collected after 3-day repeated oral administrations of alpelisib as monotherapy (Day 3) and after 22-day repeated oral administrations of alpelisib in combination with repeated doses of amcenestrant (Day 22). PK parameters were determined by non-compartmental analysis.
Time frame: Days 3 and 22 of Cycle 1 (cycle duration=28 days)
Parts H and I: Time to Reach Maximum Plasma Concentration of Everolimus After First Dose and Repeated Oral Administrations in Combination With Amcenestrant
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of everolimus in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
Time frame: Days 1 and 22 of Cycle 1 (cycle duration=28 days)
Parts H and I: Maximum Plasma Concentration of Everolimus After First Dose and Repeated Oral Administrations in Combination With Amcenestrant
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of everolimus in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
Time frame: Days 1 and 22 of Cycle 1 (cycle duration=28 days)
Parts H and I: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours of Everolimus After First Dose and Repeated Oral Administrations in Combination With Amcenestrant
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of everolimus in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
Time frame: Days 1 and 22 of Cycle 1 (cycle duration=28 days)
Part J: Time to Reach Maximum Plasma Concentration of Abemaciclib and Its Metabolites M2, M18 and M20 After First Dose and Repeated Oral Administrations in Combination With Amcenestrant
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of abemaciclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
Time frame: Days 1 and 22 of Cycle 1 (cycle duration=28 days)
Part J: Maximum Plasma Concentration of Abemaciclib and Its Metabolites M2, M18 and M20 After First Dose and Repeated Oral Administrations in Combination With Amcenestrant
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of abemaciclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
Time frame: Days 1 and 22 of Cycle 1 (cycle duration=28 days)
Part J: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Abemaciclib and Its Metabolites M2, M18 and M20 After First Dose and Repeated Oral Administrations in Combination With Amcenestrant
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of abemaciclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
Time frame: Days 1 and 22 of Cycle 1 (cycle duration=28 days)
Parts A, B, J: Post/Pre--Treatment Ratio of 4 Beta (β)-Hydroxycholesterol
Ratios of 4β-hydroxycholesterol concentrations were calculated from plasma samples collected before and after amcenestrant administration.
Time frame: Pre-treatment on Day 1 of Cycle 1; post-treatment on Day 22 of Cycle 1, Day 1 and Day 28 (only for Part J) of Cycle 2 (cycle duration=28 days)
This study was conducted at 25 sites in 10 countries between 20-Sep-2017 and 08-Nov-2024. A total of 136 participants were enrolled in the study. Sponsor decided to prematurely stop the study, it was not linked to any safety concern.
| Milestone | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 3 | 3 | 4 | 3 | 3 | 6 | 49 | 9 | 6 | 30 | 8 | 3 | 3 | 1 | 3 | 2 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 3 | 3 | 4 | 3 | 3 | 6 | 49 | 9 | 6 | 30 | 8 | 3 | 3 | 1 | 3 | 2 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 4 | 1 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Progressive disease | 3 | 3 | 4 | 3 | 3 | 5 | 45 | 8 | 5 | 18 | 7 | 2 | 3 | 1 | 1 | 2 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Other | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 6 | 0 | 0 | 0 | 0 | 2 | 0 |
DLTs: any treatment-emergent adverse event(TEAE) related to study treatment per National Cancer Institute Common Terminology Criteria for AE scale version (v) 4.03:Grade(G)≥3 nonhematological toxicity except:G3 nausea/vomiting resolved to G≤1 in 48 hours(h),G3 diarrhea with therapy and lasting\<48h,G3 hyperglycemia resolved to G≤1 in 48h(Part H);G≥3 hematological toxicity except:G3 anemia,G4 neutropenia\<7days(d),G3 neutropenia without fever/infection,G3 thrombocytopenia without bleeding;elevated total serum bilirubin(BL)\>2xupper limit of normal(except Part F),Part F:G3 hyperglycemia not resolved to G≤2 in 7d after antidiabetic treatment,G2 hyperglycemia not resolved to G≤1 in 21d,G2 alanine aminotransferase(ALT) increase in conjunction with total blood BL G≥2 without liver metastases,G≥3 ALT/aspartate aminotransferase increase for\>4d,G3 rash/maculopapular rash not resolved to G≤1 in 7d;treatment related toxicity causing≥7d omission in Cycle 1 or \>2 weeks delay in Cycle 2 in Part C.
| Participants | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, C, F, H, J: Number of Participants With Study Treatment-Related Dose-Limiting Toxicities (DLTs) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
ORR was determined by dividing the number of participants who achieved confirmed complete response (CR) or partial response (PR) by the number of participants from the analysis population. ORR was assessed by ICR according to response evaluation criteria in solid tumors (RECIST) v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
| percentage of participants | Part B: Amcenestrant 400 mg |
|---|---|
| Part B: Objective Response Rate (ORR) as Determined by Independent Central Review (ICR) | 10.9 (4.4 to 21.5) |
AE was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which did not necessarily had a causal relationship with the treatment. SAE was any untoward medical occurrence that at any dose, resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed or worsened or became serious during the treatment period.
| Participants | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg |
|---|---|---|
| TEAEs | 30 | 1 |
| TESAEs | 8 | 1 |
AE was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which did not necessarily had a causal relationship with the treatment. SAE was any untoward medical occurrence that at any dose, resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed or worsened or became serious during the treatment period.
| Participants | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TEAEs | 3 | 3 | 4 | 3 | 3 | 6 | 49 | 9 | 6 | 8 | 3 | 3 | 3 | 2 |
| TESAEs | 0 | 1 | 1 | 0 | 1 | 3 | 15 | 2 | 1 | 6 | 1 | 0 | 0 | 1 |
ORR was determined by dividing the number of participants who achieved confirmed CR or PR by the number of participants from the analysis population. ORR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
| percentage of participants | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, B, C, D, F, H, I, J: Objective Response Rate as Determined by Investigators/Local Radiologists | 0 (NA to NA) | 33.3 (1.7 to 86.5) | 0 (NA to NA) | 0 (NA to NA) | 0 (NA to NA) | 0 (NA to NA) | 8.7 (3.0 to 18.8) | 22.2 (4.1 to 55.0) | 0 (0.0 to 39.3) | 34.5 (20.0 to 51.4) | 0 (NA to NA) | 0 (NA to NA) | 0 (NA to NA) | 0 (NA to NA) | 0 (NA to NA) | 50 (NA to NA) |
CBR was determined by dividing the number of participants who achieved confirmed CR, PR as best overall response (BOR) or stable disease (SD) for ≥24 weeks by the number of participants from the analysis population. CBR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study.
| percentage of participants | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, B, C, D, F, H, I, J: Clinical Benefit Rate (CBR) as Determined by Investigators/Local Radiologists | 0 (NA to NA) | 66.7 (13.5 to 98.3) | 75.0 (24.9 to 98.7) | 66.7 (13.5 to 98.3) | 33.3 (1.7 to 86.5) | 25.0 (1.3 to 75.1) | 26.1 (15.8 to 38.8) | 44.4 (16.9 to 74.9) | 50.0 (15.3 to 84.7) | 75.9 (59.4 to 88.1) | 14.3 (NA to NA) | 50 (NA to NA) | 33.3 (NA to NA) | 0 (NA to NA) | 66.7 (NA to NA) | 50 (NA to NA) |
CBR was determined by dividing the number of participants who achieved confirmed CR, PR as BOR or SD for ≥24 weeks by the number of participants from the analysis population. CBR was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
| percentage of participants | Part B: Amcenestrant 400 mg |
|---|---|
| Part B: Clinical Benefit Rate as Determined by Independent Central Review | 28.3 (17.6 to 41.1) |
DOR was defined as the time interval from the date of the first occurrence of confirmed CR or PR to the date of the first documentation of disease progression or death due to disease progression, whichever occurred first. DOR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, an absolute increase of at least 5 mm in the sum. Appearance of 1 or more new lesions was also considered progression.
| weeks | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, B, C, D, F, H, I, J: Duration of Response (DOR) as Determined by Investigators/Local Radiologists | — | 23.9 (NA to NA) | — | — | — | — | NA (32.14 to NA) | 32.2 (24.14 to NA) | — | 52.4 (16.00 to NA) | — | — | — | — | — | 11.43 (NA to NA) |
DOR was defined as the time interval from the date of the first occurrence of confirmed CR or PR to the date of the first documentation of disease progression or death due to disease progression, whichever occurred first. DOR was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, an absolute increase of at least 5 mm in the sum. Appearance of 1 or more new lesions was also considered progression.
| weeks | Part B: Amcenestrant 400 mg |
|---|---|
| Part B: Duration of Response as Determined by Independent Central Review | NA (18.71 to NA) |
PFS was defined as time from the date of the first treatment intake to the date of the first documentation of objective PD according to RECIST v1.1, clinical PD or death due to any cause, whichever occurred first. PFS was assessed by investigators/local radiologists. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, an absolute increase of at least 5 mm in the sum. Appearance of 1 or more new lesions was also considered progression.
| weeks | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, B, C, D, F, H, I, J: Progression-Free Survival (PFS) as Determined by Investigators/Local Radiologists | 7.3 (6.29 to 15.29) | 31.3 (5.29 to 41.71) | 31.3 (6.14 to 31.57) | 32.3 (8.43 to 90.57) | 7.9 (7.57 to 39.00) | 7.7 (7.14 to 32.00) | 8.3 (7.86 to 23.14) | 44.3 (7.43 to 80.43) | 60.0 (7.43 to NA) | 79.7 (40.00 to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) |
ORR was determined by dividing the number of participants who achieved confirmed CR or PR by the number of participants from the analysis population. ORR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The ESR1 gene mutation status (mutated or wild-type) was analyzed by multiplex droplet digital polymerase chain reaction (ddPCR) after extraction of plasma circulating deoxyribonucleic acid (DNA). The baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.
| percentage of participants | Part A and B: Amcenestrant (Dose >20 mg) | Parts C and D: Amcenestrant 200 mg + Palbociclib 125 mg |
|---|---|---|
| Wild-Type | 13.3 (4.7 to 28.0) | 33.3 (18.6 to 50.9) |
| Mutated | 3.6 (0.2 to 15.9) | 27.3 (7.9 to 56.4) |
| Unknown | 0 (NA to NA) | — |
ORR was determined by dividing the number of participants who achieved confirmed CR or PR by the number of participants from the analysis population. ORR was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The ESR1 gene mutation status (mutated or wild-type) was analyzed by multiplex ddPCR after extraction of plasma circulating DNA. The baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.
| percentage of participants | Part B: Amcenestrant 400 mg |
|---|---|
| Wild-Type | 15.4 (5.4 to 31.8) |
| Mutated | 5.3 (0.3 to 22.6) |
| Unknown | 0 (NA to NA) |
CBR was determined by dividing the number of participants who achieved confirmed CR, PR as BOR or SD for ≥24 weeks by the number of participants from analysis population. CBR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The ESR1 gene mutation status (mutated or wild-type) was analyzed by multiplex ddPCR after extraction of plasma circulating DNA. Baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.
| percentage of participants | Part A and B: Amcenestrant (Dose >20 mg) | Parts C and D: Amcenestrant 200 mg + Palbociclib 125 mg |
|---|---|---|
| Wild-Type | 36.7 (22.1 to 53.3) | 70.4 (52.9 to 84.3) |
| Mutated | 32.1 (17.9 to 49.4) | 63.6 (35.0 to 86.5) |
| Unknown | 0 (NA to NA) | — |
The time to first confirmed response was defined as the time interval from the date of first administration of the study treatment to the date of the first occurrence of confirmed CR or PR. The time to first confirmed response was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
| weeks | Part B: Amcenestrant 400 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg |
|---|---|---|---|
| Parts B, D, I: Time to First Confirmed Response as Determined by Investigators/Local Radiologists | 8.1 (8 to 40) | 16.2 (8 to 32) | — |
The time to first confirmed response was defined as the time interval from the date of first administration of the study treatment to the date of the first occurrence of confirmed CR or PR. The time to first confirmed response was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
| weeks | Part B: Amcenestrant 400 mg |
|---|---|
| Part B: Time to First Confirmed Response as Determined by Independent Central Review | 31.1 (23 to 68) |
Inhibition of estrogen receptor (ER) occupancy investigation using 18F-FES-PET imaging was a limited invasive procedure that allowed assessment of ER presence by assessing the binding of radiolabeled estradiol, the ligand of ER (signal extinction). Number of participants with percentage reduction (≥90%, ≥70%, ≥50% and ≥30%) in 18F-FES-PET signal are reported. The baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.
| Participants | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID |
|---|---|---|---|---|---|---|
| ≥90% Reduction | 0 | 3 | 2 | 2 | 3 | 2 |
| ≥70% Reduction | 1 | 3 | 3 | 3 | 3 | 2 |
| ≥50% Reduction | 1 | 3 | 4 | 3 | 3 | 2 |
| ≥30% Reduction | 1 | 3 | 4 | 3 | 3 | 3 |
Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. Pharmacokinetic (PK) parameters were determined by non-compartmental analysis. LLOQ value for amcenestrant was 5 nanograms per milliliter (ng/mL).
| hour | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, B, C, D, H, I, J: Time Interval Between Administration and the Sampling Preceding the First Concentration Above the Lower Limit of Quantification (LLOQ) (Tlag) of Amcenestrant After a Single Oral Administration | 0.00 (0.00 to 0.50) | 0.00 (0.00 to 1.58) | 0.00 (0.00 to 0.50) | 0.00 (0.00 to 0.00) | 0.00 (0.00 to 0.00) | 0.00 (0.00 to 0.00) | 0.00 (0.00 to 1.02) | 0.00 (0.00 to 1.00) | 0.00 (0.00 to 1.00) | 0.470 (0.00 to 1.08) | 0.00 (0.00 to 0.980) | 0.00 (0.00 to 0.980) | 0.00 (0.00 to 0.00) | 0.00 (0.00 to 0.00) | 0.00 (0.00 to 0.00) |
Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.
| hour | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, B, C, D, H, I, J: Time to Reach Maximum Plasma Concentration (Tmax) of Amcenestrant After a Single Oral Administration | 1.52 (1.50 to 2.00) | 3.00 (3.00 to 24.77) | 2.98 (1.98 to 4.02) | 3.00 (1.50 to 3.83) | 3.03 (2.02 to 4.00) | 2.98 (2.00 to 5.95) | 3.98 (1.97 to 9.98) | 5.82 (2.00 to 9.12) | 4.97 (1.00 to 6.13) | 3.03 (2.00 to 23.90) | 4.02 (3.00 to 4.05) | 3.98 (2.00 to 7.92) | 4.00 (4.00 to 4.00) | 3.88 (3.00 to 4.00) | 3.50 (3.00 to 4.00) |
Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.
| ng/mL | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, B, C, D, H, I, J: Maximum Plasma Concentration (Cmax) of Amcenestrant After a Single Oral Administration | 187 ± 46.7 | 1310 ± 1380 | 1650 ± 1340 | 4740 ± 2920 | 7010 ± 4180 | 4620 ± 2740 | 6020 ± 2810 | 2270 ± 1130 | 5470 ± 1280 | 2500 ± 1110 | 1700 ± 355 | 1940 ± 664 | 2330 ± NA | 4500 ± 2860 | 5360 ± 750 |
Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis. tau=12 h for Part A BID dosing and 24 h for other parts.
| ng*h/mL | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, B, C, D, H, I, J: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Dosing Interval (AUC0-tau) of Amcenestrant After a Single Oral Administration | 1040 ± 560 | 9140 ± 8730 | 13600 ± 13800 | 40400 ± 17500 | 61100 ± 36300 | 28200 ± 16900 | 50900 ± 26000 | 21300 ± 5910 | 46400 ± 4400 | 21400 ± 10000 | 14100 ± 3190 | 20900 ± 4330 | 17900 ± NA | 36500 ± 25100 | 38000 ± 13800 |
Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.
| hour | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, B, C, D, F, H, I, J: Time to Reach Maximum Plasma Concentration of Amcenestrant After Repeated Oral Administrations | 2.17 (2.00 to 4.02) | 2.97 (2.93 to 3.00) | 2.07 (2.00 to 3.03) | 2.95 (2.02 to 3.78) | 3.00 (3.00 to 4.00) | 2.98 (2.00 to 3.00) | 3.00 (1.02 to 6.00) | 4.88 (1.37 to 8.17) | 4.00 (1.83 to 10.00) | 4.00 (1.75 to 6.00) | 3.22 (1.97 to 3.98) | 2.47 (2.03 to 4.03) | 4.17 (3.95 to 5.92) | 4.07 (4.07 to 4.07) | 2.67 (2.05 to 3.00) | 3.33 (3.33 to 3.33) |
Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.
| ng/mL | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, B, C, D, F, H, I, J: Maximum Plasma Concentration of Amcenestrant After Repeated Oral Administrations | 218 ± 95.3 | 2390 ± 1200 | 2150 ± 873 | 4020 ± 2460 | 5570 ± 962 | 5200 ± 296 | 4380 ± 1230 | 2060 ± 831 | 4350 ± 3190 | 2120 ± 691 | 4230 ± 1250 | 3300 ± 1390 | 2760 ± 411 | 848 ± NA | 3350 ± 1230 | 3820 ± NA |
Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis. tau=12 h for Part A BID dosing and 24 h for other parts.
| ng*h/mL | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts A, B, C, D, F, H, I, J: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Dosing Interval of Amcenestrant After Repeated Oral Administrations | 1630 ± 1120 | 15900 ± 7350 | 13900 ± 4380 | 36800 ± 23500 | 42700 ± 11200 | 36500 ± 7680 | 43200 ± 16200 | 20600 ± 7520 | 33100 ± 11400 | 17600 ± 7540 | 30600 ± 11900 | 28300 ± 21100 | 25000 ± 7180 | 8270 ± NA | 26600 ± 12900 | 30300 ± NA |
Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations.
| ng/mL | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 8 | 0 ± NA | 91.4 ± NA | 159 ± 35.8 | 871 ± NA | 302 ± NA | 2220 ± 1100 | 665 ± 581 | 348 ± 180 | 389 ± 234 | 303 ± 294 | — | — | — | — | — | — |
| Cycle 1 Day 15 | — | — | — | — | — | — | 553 ± 605 | 328 ± 168 | 243 ± 151 | 226 ± 198 | — | — | — | — | — | — |
| Cycle 1 Day 21 | — | — | — | — | — | — | — | 359 ± 132 | 297 ± 144 | 223 ± 187 | — | — | — | — | — | — |
| Cycle 1 Day 22 | 6.80 ± 9.62 | 75.1 ± NA | 76.1 ± 56.0 | 388 ± 327 | 348 ± 197 | 1510 ± 1030 | 598 ± 460 | — | — | — | 410 ± 449 | 326 ± 216 | 346 ± 128 | 114 ± NA | 214 ± 138 | 229 ± NA |
Urine samples were collected at the specified timepoints for the measurement of amcenestrant amount excreted in urine.
| ng | Part B: Amcenestrant 400 mg |
|---|---|
| Part B: Cumulated Amount of Amcenestrant Excreted in Urine From Time 0 to 24 Hours (Ae0-24) | 30800 ± 36100 |
The food effect was assessed by comparing the geometric means of AUC0-24 between Cycle 1 Day 1 (fasted condition) and Cycle 1 Day 3 (fed condition) in Part A.
| ratio | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg |
|---|---|---|---|---|---|
| Part A (QD Regimen): Geometric Mean Ratio of Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24) of Amcenestrant | 1.05 (0.60 to 1.83) | 0.69 (0.31 to 1.50) | 1.77 (1.20 to 2.62) | 1.12 (0.51 to 2.45) | 1.38 (0.88 to 2.17) |
The food effect was assessed by comparing the geometric means of Cmax between Cycle 1 Day 1 (fasted condition) and Cycle 1 Day 3 (fed condition) in Part A.
| ratio | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg |
|---|---|---|---|---|---|
| Part A (QD Regimen): Geometric Mean Ratio of Maximum Plasma Concentration of Amcenestrant | 0.80 (0.41 to 1.58) | 0.41 (0.16 to 1.07) | 1.67 (1.04 to 2.69) | 1.38 (0.53 to 3.59) | 1.43 (0.83 to 2.48) |
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 21) of palbociclib in combination with amcenestrant for the measurement of palbociclib concentrations. PK parameters were determined by non-compartmental analysis.
| hour | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg |
|---|---|---|---|
| Cycle 1 Day 1 | 5.70 (3.00 to 10.00) | 3.99 (2.02 to 7.98) | 6.00 (2.07 to 24.00) |
| Cycle 1 Day 21 | 4.10 (1.93 to 9.97) | 6.00 (3.02 to 8.08) | 4.75 (3.00 to 9.58) |
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 21) of palbociclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
| ng/mL | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg |
|---|---|---|---|
| Cycle 1 Day 1 | 70.4 ± 26.1 | 64.7 ± 28.4 | 62.3 ± 17.5 |
| Cycle 1 Day 21 | 98.1 ± 37.6 | 59.4 ± 28.1 | 96.3 ± 34.9 |
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 21) of palbociclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
| ng*h/mL | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg |
|---|---|---|---|
| Cycle 1 Day 1 | 1040 ± 257 | 889 ± 376 | 949 ± 265 |
| Cycle 1 Day 21 | 1660 ± 751 | 823 ± 266 | 1570 ± 523 |
Blood samples were collected after 3-day repeated oral administrations of alpelisib as monotherapy (Day 3) and after 22-day repeated oral administrations of alpelisib in combination with repeated doses of amcenestrant (Day 22). PK parameters were determined by non-compartmental analysis.
| hour | Part F: Amcenestrant 200 mg + Alpelisib 300 mg |
|---|---|
| Cycle 1 Day 3 | 3.02 (1.02 to 9.00) |
| Cycle 1 Day 22 | 1.69 (1.25 to 2.12) |
Blood samples were collected after 3-day repeated oral administrations of alpelisib as monotherapy (Day 3) and after 22-day repeated oral administrations of alpelisib in combination with repeated doses of amcenestrant (Day 22). PK parameters were determined by non-compartmental analysis.
| ng/mL | Part F: Amcenestrant 200 mg + Alpelisib 300 mg |
|---|---|
| Cycle 1 Day 3 | 2430 ± 631 |
| Cycle 1 Day 22 | 3480 ± 516 |
Blood samples were collected after 3-day repeated oral administrations of alpelisib as monotherapy (Day 3) and after 22-day repeated oral administrations of alpelisib in combination with repeated doses of amcenestrant (Day 22). PK parameters were determined by non-compartmental analysis.
| ng*h/mL | Part F: Amcenestrant 200 mg + Alpelisib 300 mg |
|---|---|
| Cycle 1 Day 3 | 28700 ± 7890 |
| Cycle 1 Day 22 | 27300 ± 6910 |
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of everolimus in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
| hour | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg |
|---|---|---|---|
| Cycle 1 Day 1 | 1.02 (1.00 to 3.00) | 2.00 (0.98 to 3.02) | 1.00 (1.00 to 1.00) |
| Cycle 1 Day 22 | 1.00 (0.97 to 1.47) | 2.08 (0.98 to 3.03) | 1.10 (1.10 to 1.10) |
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of everolimus in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
| ng/mL | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg |
|---|---|---|---|
| Cycle 1 Day 1 | 38.7 ± 21.9 | 64.8 ± 3.54 | 43.5 ± NA |
| Cycle 1 Day 22 | 24.4 ± 6.32 | 37.6 ± 15.5 | 46.7 ± NA |
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of everolimus in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
| ng*h/mL | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg |
|---|---|---|---|
| Cycle 1 Day 1 | 210 ± 117 | 381 ± 159 | 246 ± NA |
| Cycle 1 Day 22 | 144 ± 35.0 | 319 ± 156 | 295 ± NA |
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of abemaciclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
| hour | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|
| Abemaciclib: Cycle 1 Day 1 | 5.75 (3.00 to 9.00) | 6.00 (4.00 to 8.00) |
| Abemaciclib: Cycle 1 Day 22 | 3.00 (2.67 to 4.03) | 8.00 (8.00 to 8.00) |
| M2: Cycle 1 Day 1 | 3.88 (3.00 to 4.00) | 6.50 (4.00 to 9.00) |
| M2: Cycle 1 Day 22 | 2.67 (1.03 to 3.00) | 4.00 (4.00 to 4.00) |
| M18: Cycle 1 Day 1 | 4.00 (3.88 to 8.00) | 8.00 (8.00 to 8.00) |
| M18: Cycle 1 Day 22 | 2.67 (1.97 to 4.00) | 4.00 (4.00 to 4.00) |
| M20: Cycle 1 Day 1 | 8.07 (3.00 to 9.00) | 8.50 (8.00 to 9.00) |
| M20: Cycle 1 Day 22 | 1.03 (0.00 to 4.67) | 8.67 (8.67 to 8.67) |
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of abemaciclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
| ng/mL | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|
| Abemaciclib: Cycle 1 Day 1 | 91.6 ± 58.4 | 152 ± 44.5 |
| Abemaciclib: Cycle 1 Day 22 | 109 ± 45.6 | 87.8 ± NA |
| M2: Cycle 1 Day 1 | 17.8 ± 3.46 | 55.3 ± 22.0 |
| M2: Cycle 1 Day 22 | 69.1 ± 20.5 | 106 ± NA |
| M18: Cycle 1 Day 1 | 6.37 ± 0.514 | 22.0 ± 4.24 |
| M18: Cycle 1 Day 22 | 35.1 ± 17.2 | 89.5 ± NA |
| M20: Cycle 1 Day 1 | 31.2 ± 2.84 | 65.5 ± 8.13 |
| M20: Cycle 1 Day 22 | 100 ± 17.3 | 153 ± NA |
Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of abemaciclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.
| ng*h/mL | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|
| Abemaciclib: Cycle 1 Day 1 | 994 ± 700 | 1330 ± 478 |
| Abemaciclib: Cycle 1 Day 22 | 1050 ± 532 | — |
| M2: Cycle 1 Day 1 | 160 ± 45.0 | 554 ± NA |
| M2: Cycle 1 Day 22 | 610 ± 170 | 1130 ± NA |
| M18: Cycle 1 Day 1 | 47.6 ± 0.468 | 218 ± NA |
| M18: Cycle 1 Day 22 | 314 ± 141 | 926 ± NA |
| M20: Cycle 1 Day 1 | 295 ± 9.12 | — |
| M20: Cycle 1 Day 22 | 997 ± 219 | — |
Ratios of 4β-hydroxycholesterol concentrations were calculated from plasma samples collected before and after amcenestrant administration.
| ratio | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 22/Cycle 1 Day 1 | 0.817 ± 0.168 | 1.18 ± 0.294 | 1.29 ± 0.263 | 1.61 ± 0.336 | 2.24 ± 1.29 | 2.17 ± 0.377 | 1.68 ± 0.577 | — | — |
| Cycle 2 Day 1/Cycle 1 Day 1 | 1.09 ± 0.304 | 1.13 ± 0.432 | 1.39 ± 0.207 | 1.83 ± 0.569 | 2.40 ± 0.559 | 2.99 ± 1.58 | 1.89 ± 0.627 | — | — |
Collected over Adverse events were collected from first dose of study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration; approximately 94, 282, 144, 232, 96, 59, 11, 130 weeks for Parts A, B, C, D, F, H, I, J respectively. All-cause mortality (deaths) were collected from first dose of study treatment administration (Day 1) to the end of follow-up for death for each participant; up to approximately 372 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part A: Amcenestrant 20 mg | 1/3 (33.3%) | 0/3 (0%) | 3/3 (100%) |
| Part A: Amcenestrant 150 mg | 1/3 (33.3%) | 1/3 (33.3%) | 3/3 (100%) |
| Part A: Amcenestrant 200 mg | 0/4 (0%) | 1/4 (25%) | 4/4 (100%) |
| Part A: Amcenestrant 400 mg | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Part A: Amcenestrant 600 mg | 1/3 (33.3%) | 1/3 (33.3%) | 3/3 (100%) |
| Part A: Amcenestrant 300 mg BID | 0/6 (0%) | 3/6 (50%) | 6/6 (100%) |
| Part B: Amcenestrant 400 mg | 4/49 (8.2%) | 15/49 (30.6%) | 49/49 (100%) |
| Part C: Amcenestrant 200 mg + Palbociclib 125 mg | 1/9 (11.1%) | 2/9 (22.2%) | 9/9 (100%) |
| Part C: Amcenestrant 400 mg + Palbociclib 125 mg | 0/6 (0%) | 1/6 (16.7%) | 6/6 (100%) |
| Part D: Amcenestrant 200 mg + Palbociclib 125 mg | 0/30 (0%) | 8/30 (26.7%) | 29/30 (96.7%) |
| Part F: Amcenestrant 200 mg + Alpelisib 300 mg | 2/8 (25%) | 6/8 (75%) | 8/8 (100%) |
| Part H: Amcenestrant 200 mg + Everolimus 5 mg | 0/3 (0%) | 1/3 (33.3%) | 3/3 (100%) |
| Part H: Amcenestrant 200 mg + Everolimus 10 mg | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Part I: Amcenestrant 200 mg + Everolimus 10 mg | 0/1 (0%) | 1/1 (100%) | 1/1 (100%) |
| Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID | 0/2 (0%) | 1/2 (50%) | 2/2 (100%) |
| Event | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SepsisInfections and infestations | 0/3 | 0/3 | 0/4 | 0/3 | 0/3 | 0/6 | 0/49 | 0/9 | 0/6 | 0/30 | 0/8 | 0/3 | 0/3 | 1/1 | 0/3 | 0/2 |
| ConstipationGastrointestinal disorders | 0/3 | 0/3 | 0/4 | 0/3 | 0/3 | 0/6 | 0/49 | 0/9 | 0/6 | 0/30 | 0/8 | 0/3 | 0/3 | 0/1 | 0/3 | 1/2 |
| PneumothoraxRespiratory, thoracic and mediastinal disorders | 0/3 | 0/3 | 0/4 | 0/3 | 0/3 | 1/6 | 0/49 | 0/9 | 0/6 | 0/30 | 0/8 | 1/3 | 0/3 | 0/1 | 0/3 | 0/2 |
| Back PainMusculoskeletal and connective tissue disorders | 0/3 | 1/3 | 0/4 | 0/3 | 0/3 | 0/6 | 0/49 | 0/9 | 0/6 | 1/30 | 0/8 | 0/3 | 0/3 | 0/1 | 0/3 | 0/2 |
| Disease ProgressionGeneral disorders | 0/3 | 1/3 | 0/4 | 0/3 | 0/3 | 0/6 | 1/49 | 0/9 | 0/6 | 0/30 | 0/8 | 0/3 | 0/3 | 0/1 | 0/3 | 0/2 |
| FatigueGeneral disorders | 0/3 | 0/3 | 0/4 | 0/3 | 1/3 | 0/6 | 0/49 | 0/9 | 0/6 | 0/30 | 0/8 | 0/3 | 0/3 | 0/1 | 0/3 | 0/2 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/3 | 0/3 | 1/4 | 0/3 | 0/3 | 0/6 | 2/49 | 0/9 | 0/6 | 0/30 | 1/8 | 0/3 | 0/3 | 0/1 | 0/3 | 0/2 |
| HypophosphataemiaMetabolism and nutrition disorders | 0/3 | 0/3 | 0/4 | 0/3 | 0/3 | 1/6 | 0/49 | 0/9 | 0/6 | 0/30 | 0/8 | 0/3 | 0/3 | 0/1 | 0/3 | 0/2 |
| Superior Vena Cava SyndromeVascular disorders | 0/3 | 0/3 | 0/4 | 0/3 | 0/3 | 1/6 | 0/49 | 0/9 | 0/6 | 0/30 | 0/8 | 0/3 | 0/3 | 0/1 | 0/3 | 0/2 |
| Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders | 0/3 | 0/3 | 0/4 | 0/3 | 0/3 | 1/6 | 2/49 | 0/9 | 0/6 | 0/30 | 0/8 | 0/3 | 0/3 | 0/1 | 0/3 | 0/2 |
| Event | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Decreased AppetiteMetabolism and nutrition disorders | 0/3 | 1/3 | 0/4 | 2/3 | 3/3 | 1/6 | 7/49 | 0/9 | 2/6 | 1/30 | 3/8 | 2/3 | 0/3 | 0/1 | 0/3 | 0/2 |
| DiarrhoeaGastrointestinal disorders | 0/3 | 1/3 | 2/4 | 3/3 | 0/3 | 3/6 | 8/49 | 1/9 | 3/6 | 8/30 | 6/8 | 1/3 | 2/3 | 1/1 | 2/3 | 1/2 |
| Dry SkinSkin and subcutaneous tissue disorders | 0/3 | 1/3 | 0/4 | 0/3 | 1/3 | 0/6 | 3/49 | 2/9 | 0/6 | 6/30 | 1/8 | 0/3 | 2/3 | 1/1 | 1/3 | 0/2 |
| RashSkin and subcutaneous tissue disorders | 0/3 | 0/3 | 1/4 | 0/3 | 1/3 | 2/6 | 1/49 | 0/9 | 0/6 | 6/30 | 2/8 | 0/3 | 1/3 | 1/1 | 0/3 | 0/2 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/3 | 1/3 | 1/4 | 1/3 | 1/3 | 1/6 | 10/49 | 2/9 | 2/6 | 8/30 | 1/8 | 1/3 | 3/3 | 0/1 | 1/3 | 0/2 |
| FatigueGeneral disorders | 1/3 | 0/3 | 1/4 | 0/3 | 1/3 | 1/6 | 12/49 | 2/9 | 1/6 | 12/30 | 2/8 | 2/3 | 2/3 | 1/1 | 2/3 | 0/2 |
| Weight DecreasedInvestigations | 0/3 | 0/3 | 0/4 | 0/3 | 0/3 | 0/6 | 2/49 | 0/9 | 0/6 | 1/30 | 0/8 | 1/3 | 0/3 | 1/1 | 0/3 | 0/2 |
| Urinary Tract InfectionInfections and infestations | 0/3 | 1/3 | 0/4 | 1/3 | 2/3 | 0/6 | 5/49 | 1/9 | 1/6 | 5/30 | 1/8 | 0/3 | 0/3 | 0/1 | 0/3 | 1/2 |
| HeadacheNervous system disorders | 0/3 | 0/3 | 0/4 | 0/3 | 1/3 | 1/6 | 3/49 | 1/9 | 0/6 | 6/30 | 1/8 | 0/3 | 2/3 | 0/1 | 2/3 | 0/2 |
| Hot FlushVascular disorders | 0/3 | 2/3 | 1/4 | 2/3 | 1/3 | 0/6 | 7/49 | 3/9 | 0/6 | 1/30 | 0/8 | 1/3 | 1/3 | 0/1 | 0/3 | 0/2 |
The safety population included all registered participants exposed to the study treatment, regardless of the amount of treatment administered.
| Age, Customized(Participants) | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| From 18 - 64 years | 1 | 3 | 3 | 1 | 3 | 5 | 29 | 6 | 2 | 19 | 4 | 2 | 2 | 1 | 2 | 0 | 83 |
| From 65 - 84 years | 2 | 0 | 1 | 2 | 0 | 0 | 17 | 3 | 4 | 9 | 4 | 1 | 1 | 0 | 1 | 2 | 47 |
| 85 years and over | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
| Sex: Female, Male(Participants) | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | 3 | 3 | 4 | 3 | 3 | 6 | 49 | 9 | 6 | 30 | 8 | 3 | 3 | 1 | 3 | 2 | 136 |
| Male | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Part A: Amcenestrant 20 mg | Part A: Amcenestrant 150 mg | Part A: Amcenestrant 200 mg | Part A: Amcenestrant 400 mg | Part A: Amcenestrant 600 mg | Part A: Amcenestrant 300 mg BID | Part B: Amcenestrant 400 mg | Part C: Amcenestrant 200 mg + Palbociclib 125 mg | Part C: Amcenestrant 400 mg + Palbociclib 125 mg | Part D: Amcenestrant 200 mg + Palbociclib 125 mg | Part F: Amcenestrant 200 mg + Alpelisib 300 mg | Part H: Amcenestrant 200 mg + Everolimus 5 mg | Part H: Amcenestrant 200 mg + Everolimus 10 mg | Part I: Amcenestrant 200 mg + Everolimus 10 mg | Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID | Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| White | 1 | 3 | 1 | 3 | 2 | 3 | 35 | 4 | 4 | 29 | 6 | 0 | 3 | 0 | 2 | 2 | 98 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Not reported | 2 | 0 | 2 | 0 | 1 | 2 | 13 | 3 | 2 | 0 | 2 | 3 | 0 | 1 | 1 | 0 | 32 |
| Unknown | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Ran from Sep 2017 to primary completion in Nov 2024, 85 months.
Results were first posted in Nov 2025, 1 year after primary completion.
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Studies of the drug tested here: Amcenestrant