A Phase 2 interventional study of Amcenestrant and Fulvestrant in Breast Cancer Metastatic, sponsored by Sanofi. Terminated at 109 sites in 23 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-24.
Sponsored by Sanofi · Phase 2, Interventional, and Treatment
Primary Objective:
To determine whether amcenestrant per overall survival (os) improves progression free survival (PFS) when compared with an endocrine monotherapy of the choice of the physician, in participants with metastatic or locally advanced breast cancer
Secondary Objectives:
The duration of the study for an individual participant will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1 cycle (28 days of study treatment), and an end of treatment (EOT) visit at least 30 days (or until the participant receive another anticancer therapy, whichever is earlier) following the last administration of study treatment. Study treatment may continue until precluded by unacceptable toxicity, disease progression, death or upon participant's request to stop treatment, or Investigator decision, whichever occurs first.
An extension of recruitment for Chinese participants is planned in this study: After completion of randomization in the global part of the study, randomization will continue in China until approximately 90 Chinese participants are randomized.
Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.
Of its 198 completed or terminated interventional studies of FDA-regulated products, 118 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion criteria:
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Daily amcenestrant dose administered orally under fed or fast condition
Drug: Amcenestrant
Control treatment of the choice of the physician depending on each participant's medical condition and in accordance with the approved label may include 1 of the following treatments used as monotherapy. Fulvestrant Aromatase inhibitors (anastrozole, letrozole, exemestane) Selective estrogen receptor modulator (Tamoxifen)
Drug: Fulvestrant · Drug: Anastrozole · Drug: Letrozole · Drug: Exemestane · Drug: Tamoxifen
Pharmaceutical form: Capsule Route of administration: Oral
Pharmaceutical form: Solution for injection Route of administration: Intramuscular
Also known as: Faslodex®
Pharmaceutical form:Tablets or capsules Route of administration: Oral
Also known as: Arimidex®/Anastrozole Generics
Pharmaceutical form: Tablets or capsules Route of administration: Oral
Also known as: Femara®/Letrozole Generics
Pharmaceutical form: Tablets or capsules Route of administration: Oral
Also known as: Aromasin®/Exemestane Generics
Pharmaceutical form: Tablets or capsules Route of administration: Oral
Also known as: Nolvadex®/Tamoxifen Generics
Progression Free Survival (PFS)
PFS is defined as the time in months interval from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) assessed by independent central review (ICR) or death (due to any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
Time frame: From randomization to the date of first documented tumor progression or death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
Chinese Cohort: Progression Free Survival
PFS is defined as the time in months interval from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by ICR or death (due to any cause), whichever comes first. PD as per RECIST 1.1: at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
Time frame: From randomization to the date of first documented tumor progression or death due to any cause or data cut-off date whichever comes first, up to primary completion date of 15-Feb-2022, a maximum of 121 weeks
Overall Survival (OS)
OS is defined as the time interval from the date of randomization to the date of documented death (due to any cause). In the absence of observation of death, survival time was censored to last date the participant is known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.
Time frame: From randomization to the death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
Percentage of Participants With Objective Response
Objective response is defined as percentage of participants having a partial response (PR) or complete response (CR) according to the RECIST version 1.1 assessed by ICR. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 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 randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
Percentage of Participants With Disease Control
Disease control is defined as percentage of participants having a confirmed CR, PR, or stable disease (SD) or Non-CR/Non-PD as BOR determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
Time frame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
Percentage of Participants With Clinical Benefit
Clinical Benefit is defined as percentage of participants having a confirmed CR, PR, SD, or Non-CR/Non-PD for at least 24 weeks determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
Time frame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
Duration of Response (DOR)
DOR is defined as time (in months) from first documented evidence of CR or PR until progressive disease (PD) determined by ICR as per RECIST 1.1 or death from any cause, whichever occurs first. For participants with ongoing response at the time of the analysis, DOR was censored at the date of the last valid disease assessment not showing documented progression performed before the initiation of a new anticancer treatment (if any). As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
Time frame: From the date of first response to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
Progression Free Survival (PFS) According to Estrogen Receptor 1 Gene (ESR1) Mutation Status
PFS defined as the time (in months) interval from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by ICR or death (due to any cause), whichever comes first. Progression as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. The mutation status (wild type, mutant) of twelve specific mutations of the ESR1 gene was determined by multiplex droplet digital polymerase chain reaction (ddPCR), including their mutant frequency and concentration. Here, PFS is reported based on the ESR1 mutation status of participants: wild type and mutants. ESR1 was the gene encoding estrogen receptor alpha. ESR1 mutant type breast cancer was a disease where the ESR1 gene had a mutation (i.e., a type of error). ESR1 wild type breast cancer was a disease where the ESR1 gene was normal without a mutation. Analysis was performed by Kaplan-Meier method.
Time frame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
Pharmacokinetics: Plasma Concentrations of Amcenestrant
Amcenestrant plasma concentrations at specified time points are reported.
Time frame: Cycle 1 Day 1: 1.5 hours(h), 4h post-dose, Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 1.5h, 4h, 8h post-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 6 Day 1: pre-dose
Within-Participant Steady State Ctrough of Amcenestrant
Within-participant Steady state Ctrough was defined as the median value of the Ctrough across study using plasma concentration of predose samples at Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 for each individual participant. Average (mean) of all calculated Ctrough values for all participants across study (Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 ) was derived and reported in this outcome measure.
Time frame: Predose on Cycle 1 Day 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4 Day 1; Cycle 6 Day 1
Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Domain Scores
EORTC-QLQ-C30: cancer-specific instrument with 30 questions for evaluation of new chemotherapy \& assessment of participant reported outcome. These include 5 functional scales, 9 symptom scales, \& Global Health Status/quality of life scale (GHS/QoL). All 14 items/domains were scored on scale of 1 (not at all) to 4 (very much) and GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional \& GHS/QoL = higher level of functioning, \& higher score for symptoms scales = higher symptom burden. Least Square (LS) mean and Standard Error (SE) are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported in this outcome measure.
Time frame: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Visual Analog Scale (VAS) Score
EQ-5D-5L is a standardized measure of health status, provides a simple, generic measure of health for clinical and economic appraisal, and consists of 2 sections: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L VAS. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported in this outcome measure.
Time frame: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health Utility Index Value
EQ-5D-5L: consists of 2 sections: EQ-5D-5L health state utility index (descriptive system) \& VAS. The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort \& anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, \& extreme problems. Response options are measured with 5-point Likert scale (for 5L version). The EQ-5D-5L responses are converted into single index utility score between 0 to 1, where higher score indicates better health state \& lower score indicate worse health state. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported in this outcome measure.
Time frame: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC-QLQ-BR23) Domain Scores
QLQ-BR23: disease-specific Health-related QOL assesses impact of breast cancer \& side effects of treatment. EORTC-QLQ-BR23 contains 23 items: multi-item scales \& single-item measures. 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) \& 4 scales related to symptoms of disease or treatment (arm symptoms, breast symptoms, systemic therapy side effects, \& upset by hair loss). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported.
Time frame: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])
Chinese Cohort: Overall Survival
OS is defined as the time interval from the date of randomization to the date of documented death (due to any cause). In the absence of observation of death, survival time was censored to last date the participant is known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.
Time frame: From randomization to the death due to any cause or data cut-off date whichever comes first (maximum duration: 183 weeks)
Chinese Cohort: Percentage of Participants With Objective Response
Objective response is defined as percentage of participants having a PR or CR according to the RECIST version 1.1 assessed by ICR. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have 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 randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 183 weeks)
Chinese Cohort: Percentage of Participants With Disease Control
Disease control is defined as percentage of participants having a confirmed CR, PR, or SD or Non-CR/Non-PD as BOR determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
Time frame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 183 weeks)
Chinese Cohort: Percentage of Participants With Clinical Benefit
Clinical benefit is defined as percentage of participants having a confirmed CR, PR, SD, or Non-CR/Non-PD for at least 24 weeks determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
Time frame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 183 weeks)
Chinese Cohort: Duration of Response
DOR is defined as time (in months) from first documented evidence of CR or PR until PD determined by ICR as per RECIST 1.1 or death from any cause, whichever occurs first. For participants with ongoing response at the time of the analysis, DOR was censored at the date of the last valid disease assessment not showing documented progression performed before the initiation of a new anticancer treatment (if any). As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
Time frame: From the date of first response to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 183 weeks)
Chinese Cohort: Progression Free Survival According to Estrogen Receptor 1 Gene Mutation Status
PFS defined as the time (in months) interval from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by ICR or death (due to any cause), whichever comes first. Progression as per RECIST 1.1: at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. The mutation status (wild type, mutant) of twelve specific mutations of the ESR1 gene was determined by multiplex ddPCR, including their mutant frequency and concentration. Here, PFS is reported based on the ESR1 mutation status of participants: wild type and mutants. ESR1 was the gene encoding estrogen receptor alpha. ESR1 mutant type breast cancer was a disease where the ESR1 gene had a mutation (i.e., a type of error). ESR1 wild type breast cancer was a disease where the ESR1 gene was normal without a mutation. Analysis was performed by Kaplan-Meier method.
Time frame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 183 weeks)
Chinese Cohort: Plasma Concentration of Amcenestrant
Amcenestrant plasma concentrations at specified time points are reported.
Time frame: Cycle 1 Day 1: 1.5 hours(h), 4h post-dose, Cycle 1 Day 15: pre-dose; Cycle 2 Day 1: pre-dose, 1.5h, 4h, 8h post-dose; Cycles 3, 4, and 6 Day 1: pre-dose
Chinese Cohort: Within-Participant Steady State Ctrough of Amcenestrant
Within-participant Steady state Ctrough was defined as the median value of the Ctrough across study using plasma concentration of pre-dose samples at Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 for each individual participant. Average (mean) of all calculated Ctrough values for all participants across study (Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6) was derived and reported in this outcome measure.
Time frame: Pre-dose on Cycle 1 Day 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4 Day 1; Cycle 6 Day 1
Chinese Cohort: Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Domain Scores
EORTC-QLQ-C30: cancer-specific instrument with 30 questions for evaluation of new chemotherapy \& assessment of participant reported outcome. These include 5 functional scales, 9 symptom scales, \& Global Health Status/quality of life scale (GHS/QoL). All 14 items/domains were scored on scale of 1 (not at all) to 4 (very much) and GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional \& GHS/QoL = higher level of functioning, \& higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., 183 weeks) was reported in this outcome measure.
Time frame: Baseline and up to 183 weeks
Chinese Cohort: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels Score: Visual Analog Scale Score
EQ-5D-5L is a standardized measure of health status, provides a simple, generic measure of health for clinical and economic appraisal, and consists of 2 sections: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L VAS. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., 183 weeks) was reported in this outcome measure.
Time frame: Baseline and up to 183 weeks
Chinese Cohort: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels Score: Health Utility Index Value
EQ-5D-5L: consists of 2 sections: EQ-5D-5L health state utility index (descriptive system) \& VAS. The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort \& anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, \& extreme problems. Response options are measured with 5-point Likert scale (for 5L version). The EQ-5D-5L responses are converted into single index utility score between 0 to 1, where higher score indicates better health state \& lower score indicate worse health state. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., 183 weeks) was reported in this outcome measure.
Time frame: Baseline and up to 183 weeks
Chinese Cohort: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module Domain Scores
QLQ-BR23: disease-specific Health-related QOL assesses impact of breast cancer \& side effects of treatment. EORTC-QLQ-BR23 contains 23 items: multi-item scales \& single-item measures. 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) \& 4 scales related to symptoms of disease or treatment (arm symptoms, breast symptoms, systemic therapy side effects, \& upset by hair loss). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., 183 weeks) was reported in this outcome measure.
Time frame: Baseline and up to 183 weeks
Main Cohort and Chinese Cohort: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was a medically important event. TEAEs were defined as AEs that developed, worsened (according to the Investigator's opinion), or became serious during the on-treatment period.
Time frame: From first dose of study treatment (Cycle 1 Day 1) up to 152 weeks for main cohort and 183 weeks for Chinese cohort
The study was conducted at 88 active centers in 22 countries. 367 participants were screened between 22 October 2019 and 15 April 2021 in main (global) cohort of which 77 were screen failures (mainly due to not meeting eligibility criteria). As pre-specified in the protocol, Chinese participants from main cohort and China cohort were pooled for purpose of analysis of Chinese cohort. 90 participants (including 13 participants from main cohort) were randomized in the Chinese cohort.
| Milestone | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|---|---|
| Started | 147 | 143 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 |
| Not completed | 147 | 143 | 0 | 0 |
| Withdrew: Adverse event | 2 | 5 | 0 | 0 |
| Withdrew: Withdrawal by subject | 6 | 3 | 0 | 0 |
| Withdrew: Progressive disease | 120 | 118 | 0 | 0 |
| Withdrew: Not related to coronavirus disease-2019 (covid-19) | 19 | 17 | 0 | 0 |
| Milestone | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|---|---|
| Started | 0 | 0 | 42 | 48 |
| Completed | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 42 | 48 |
| Withdrew: Adverse event | 0 | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 | 4 |
| Withdrew: Progressive disease | 0 | 0 | 33 | 32 |
| Withdrew: Not related to covid-19 | 0 | 0 | 7 | 10 |
| Withdrew: Related to covid-19 | 0 | 0 | 0 | 1 |
| Withdrew: Poor compliance to protocol | 0 | 0 | 1 | 0 |
OS is defined as the time interval from the date of randomization to the date of documented death (due to any cause). In the absence of observation of death, survival time was censored to last date the participant is known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.
| months | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort |
|---|---|---|
| Overall Survival (OS) | NA (18.9 to NA) | NA (21.5 to NA) |
Objective response is defined as percentage of participants having a partial response (PR) or complete response (CR) according to the RECIST version 1.1 assessed by ICR. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 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 | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort |
|---|---|---|
| Percentage of Participants With Objective Response | 8.8 (4.8 to 14.6) | 11.9 (7.1 to 18.4) |
Disease control is defined as percentage of participants having a confirmed CR, PR, or stable disease (SD) or Non-CR/Non-PD as BOR determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
| percentage of participants | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort |
|---|---|---|
| Percentage of Participants With Disease Control | 53.7 (45.3 to 62.0) | 54.5 (46.0 to 62.9) |
Clinical Benefit is defined as percentage of participants having a confirmed CR, PR, SD, or Non-CR/Non-PD for at least 24 weeks determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
| percentage of participants | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort |
|---|---|---|
| Percentage of Participants With Clinical Benefit | 29.3 (22.0 to 37.3) | 27.3 (20.2 to 35.3) |
DOR is defined as time (in months) from first documented evidence of CR or PR until progressive disease (PD) determined by ICR as per RECIST 1.1 or death from any cause, whichever occurs first. For participants with ongoing response at the time of the analysis, DOR was censored at the date of the last valid disease assessment not showing documented progression performed before the initiation of a new anticancer treatment (if any). As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
| months | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort |
|---|---|---|
| Duration of Response (DOR) | NA (3.9 to NA) | 15.1 (5.6 to NA) |
PFS defined as the time (in months) interval from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by ICR or death (due to any cause), whichever comes first. Progression as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. The mutation status (wild type, mutant) of twelve specific mutations of the ESR1 gene was determined by multiplex droplet digital polymerase chain reaction (ddPCR), including their mutant frequency and concentration. Here, PFS is reported based on the ESR1 mutation status of participants: wild type and mutants. ESR1 was the gene encoding estrogen receptor alpha. ESR1 mutant type breast cancer was a disease where the ESR1 gene had a mutation (i.e., a type of error). ESR1 wild type breast cancer was a disease where the ESR1 gene was normal without a mutation. Analysis was performed by Kaplan-Meier method.
| months | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort |
|---|---|---|
| Mutated | 2.0 (1.9 to 4.3) | 3.7 (1.9 to 7.2) |
| Wild type | 3.9 (3.6 to 9.2) | 3.5 (2.0 to 3.7) |
Amcenestrant plasma concentrations at specified time points are reported.
| nanograms per milliliter (ng/mL) | Amcenestrant- Main Cohort |
|---|---|
| Cycle 1 Day 1: 1.5h | 3185.7 ± 3145.2 |
| Cycle 1 Day 1: 4h | 4753.1 ± 3463.7 |
| Cycle 1 Day 15: Pre-dose | 516.4 ± 377.2 |
| Cycle 2 Day 1: Pre-dose | 479.1 ± 320.3 |
| Cycle 2 Day 1: 1.5h | 2719.6 ± 2374.0 |
| Cycle 2 Day 1: 4h | 3801.8 ± 2370.8 |
| Cycle 2 Day 1: 8h | 2303.8 ± 1411.4 |
| Cycle 3 Day 1: Pre-dose | 593.6 ± 815.1 |
| Cycle 4 Day 1: Pre-dose | 661.5 ± 860.5 |
| Cycle 6 Day 1: Pre-dose | 531.5 ± 468.5 |
Within-participant Steady state Ctrough was defined as the median value of the Ctrough across study using plasma concentration of predose samples at Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 for each individual participant. Average (mean) of all calculated Ctrough values for all participants across study (Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 ) was derived and reported in this outcome measure.
| ng/mL | Amcenestrant- Main Cohort |
|---|---|
| Within-Participant Steady State Ctrough of Amcenestrant | 491.35 ± 316.51 |
EORTC-QLQ-C30: cancer-specific instrument with 30 questions for evaluation of new chemotherapy \& assessment of participant reported outcome. These include 5 functional scales, 9 symptom scales, \& Global Health Status/quality of life scale (GHS/QoL). All 14 items/domains were scored on scale of 1 (not at all) to 4 (very much) and GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional \& GHS/QoL = higher level of functioning, \& higher score for symptoms scales = higher symptom burden. Least Square (LS) mean and Standard Error (SE) are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported in this outcome measure.
| score on a scale | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort |
|---|---|---|
| GHS/QoL | 1.8 ± 1.6 | 2.5 ± 1.6 |
| Physical functioning | -1.2 ± 1.3 | -3.1 ± 1.3 |
| Role functioning | -2.4 ± 1.9 | -3.0 ± 1.8 |
| Emotional functioning | -2.2 ± 1.7 | 3.0 ± 1.6 |
| Cognitive functioning | -0.9 ± 1.6 | -0.8 ± 1.5 |
| Social functioning | -2.5 ± 1.7 | -0.8 ± 1.7 |
| Fatigue | 1.1 ± 1.9 | 2.8 ± 1.9 |
| Nausea and vomiting | 1.7 ± 1.3 | 1.3 ± 1.3 |
| Pain | 1.1 ± 1.9 | 2.1 ± 1.9 |
| Dyspnoea | 1.0 ± 1.6 | 0.8 ± 1.6 |
| Insomnia | -1.1 ± 2.3 | -2.3 ± 2.2 |
| Appetite loss | 2.4 ± 2.3 | 1.2 ± 2.3 |
| Constipation | -2.3 ± 2.0 | 3.0 ± 2.0 |
| Diarrhoea | 0.3 ± 1.3 | 3.9 ± 1.3 |
| Financial difficulties | 1.7 ± 1.8 | -2.0 ± 1.8 |
EQ-5D-5L is a standardized measure of health status, provides a simple, generic measure of health for clinical and economic appraisal, and consists of 2 sections: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L VAS. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported in this outcome measure.
| score on a scale | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort |
|---|---|---|
| Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Visual Analog Scale (VAS) Score | 0.9 ± 1.4 | 0.2 ± 1.4 |
EQ-5D-5L: consists of 2 sections: EQ-5D-5L health state utility index (descriptive system) \& VAS. The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort \& anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, \& extreme problems. Response options are measured with 5-point Likert scale (for 5L version). The EQ-5D-5L responses are converted into single index utility score between 0 to 1, where higher score indicates better health state \& lower score indicate worse health state. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported in this outcome measure.
| score on a scale | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort |
|---|---|---|
| Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health Utility Index Value | -0.0 ± 0.0 | -0.0 ± 0.0 |
QLQ-BR23: disease-specific Health-related QOL assesses impact of breast cancer \& side effects of treatment. EORTC-QLQ-BR23 contains 23 items: multi-item scales \& single-item measures. 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) \& 4 scales related to symptoms of disease or treatment (arm symptoms, breast symptoms, systemic therapy side effects, \& upset by hair loss). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported.
| score on a scale | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort |
|---|---|---|
| Body image | 1.8 ± 1.7 | 2.2 ± 1.6 |
| Sexual functioning | -2.4 ± 1.3 | -2.6 ± 1.2 |
| Sexual enjoyment | -1.1 ± 3.0 | 0.4 ± 4.1 |
| Future perspective | 10.6 ± 2.7 | 12.0 ± 2.6 |
| Systemic therapy side effects | 0.2 ± 1.0 | 0.7 ± 1.0 |
| Breast symptoms | -0.4 ± 1.3 | -0.8 ± 1.2 |
| Arm symptoms | 1.8 ± 1.7 | 2.0 ± 1.7 |
| Upset by hair loss | -9.7 ± 3.9 | -10.6 ± 3.7 |
OS is defined as the time interval from the date of randomization to the date of documented death (due to any cause). In the absence of observation of death, survival time was censored to last date the participant is known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.
| months | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|
| Chinese Cohort: Overall Survival | NA (NA to NA) | NA (NA to NA) |
Objective response is defined as percentage of participants having a PR or CR according to the RECIST version 1.1 assessed by ICR. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have 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 | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|
| Chinese Cohort: Percentage of Participants With Objective Response | 10.8 (3.0 to 25.4) | 6.5 (1.4 to 17.9) |
Disease control is defined as percentage of participants having a confirmed CR, PR, or SD or Non-CR/Non-PD as BOR determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
| percentage of participants | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|
| Chinese Cohort: Percentage of Participants With Disease Control | 75.7 (58.8 to 88.2) | 73.9 (58.9 to 85.7) |
Clinical benefit is defined as percentage of participants having a confirmed CR, PR, SD, or Non-CR/Non-PD for at least 24 weeks determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
| percentage of participants | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|
| Chinese Cohort: Percentage of Participants With Clinical Benefit | 21.6 (9.8 to 38.2) | 23.9 (12.6 to 38.8) |
DOR is defined as time (in months) from first documented evidence of CR or PR until PD determined by ICR as per RECIST 1.1 or death from any cause, whichever occurs first. For participants with ongoing response at the time of the analysis, DOR was censored at the date of the last valid disease assessment not showing documented progression performed before the initiation of a new anticancer treatment (if any). As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
| months | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|
| Chinese Cohort: Duration of Response | NA (NA to NA) | NA (NA to NA) |
PFS defined as the time (in months) interval from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by ICR or death (due to any cause), whichever comes first. Progression as per RECIST 1.1: at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. The mutation status (wild type, mutant) of twelve specific mutations of the ESR1 gene was determined by multiplex ddPCR, including their mutant frequency and concentration. Here, PFS is reported based on the ESR1 mutation status of participants: wild type and mutants. ESR1 was the gene encoding estrogen receptor alpha. ESR1 mutant type breast cancer was a disease where the ESR1 gene had a mutation (i.e., a type of error). ESR1 wild type breast cancer was a disease where the ESR1 gene was normal without a mutation. Analysis was performed by Kaplan-Meier method.
| months | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|
| Mutated | 5.5 (NA to NA) | 1.8 (1.7 to NA) |
| Wild type | NA (1.8 to NA) | 1.9 (1.8 to NA) |
Amcenestrant plasma concentrations at specified time points are reported.
| ng/mL | Amcenestrant- Chinese Cohort |
|---|---|
| Cycle 1 Day 1: 1.5h | 3643.3 ± 3166.2 |
| Cycle 1 Day 1: 4h | 6015.0 ± 2887.0 |
| Cycle 1 Day 15: Pre-dose | 694.3 ± 589.4 |
| Cycle 2 Day 1: Pre-dose | 553.2 ± 316.9 |
| Cycle 2 Day 1: 1.5h | 3318.1 ± 3097.9 |
| Cycle 2 Day 1: 4h | 4912.9 ± 2513.9 |
| Cycle 2 Day 1: 8h | 3309.7 ± 1318.7 |
| Cycle 3 Day 1: Pre-dose | 521.6 ± 439.9 |
| Cycle 4 Day 1: Pre-dose | 475.1 ± 301.2 |
| Cycle 6 Day 1: Pre-dose | 598.5 ± 379.1 |
Within-participant Steady state Ctrough was defined as the median value of the Ctrough across study using plasma concentration of pre-dose samples at Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 for each individual participant. Average (mean) of all calculated Ctrough values for all participants across study (Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6) was derived and reported in this outcome measure.
| ng/mL | Amcenestrant- Chinese Cohort |
|---|---|
| Chinese Cohort: Within-Participant Steady State Ctrough of Amcenestrant | 524.51 ± 317.00 |
EORTC-QLQ-C30: cancer-specific instrument with 30 questions for evaluation of new chemotherapy \& assessment of participant reported outcome. These include 5 functional scales, 9 symptom scales, \& Global Health Status/quality of life scale (GHS/QoL). All 14 items/domains were scored on scale of 1 (not at all) to 4 (very much) and GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional \& GHS/QoL = higher level of functioning, \& higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., 183 weeks) was reported in this outcome measure.
| score on a scale | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|
| GHS/QoL | 6.4 ± 2.6 | 0.3 ± 2.5 |
| Physical functioning | 4.3 ± 1.4 | 0.9 ± 1.3 |
| Role functioning | -1.9 ± 2.5 | -0.1 ± 2.4 |
| Emotional functioning | -1.0 ± 2.0 | -1.7 ± 1.9 |
| Cognitive functioning | -0.4 ± 2.0 | -2.5 ± 1.9 |
| Social functioning | 3.0 ± 2.3 | -1.9 ± 2.2 |
| Fatigue | -1.4 ± 2.1 | 0.8 ± 2.0 |
| Nausea and vomiting | -0.9 ± 1.9 | 0.9 ± 1.8 |
| Pain | -2.1 ± 2.1 | -2.3 ± 2.0 |
| Dyspnoea | -0.3 ± 2.5 | 2.3 ± 2.4 |
| Insomnia | -0.9 ± 2.5 | -1.4 ± 2.4 |
| Appetite loss | -1.9 ± 2.7 | 2.3 ± 2.6 |
| Constipation | 2.3 ± 2.1 | 2.8 ± 2.0 |
| Diarrhoea | -0.7 ± 1.1 | -0.2 ± 1.1 |
| Financial difficulties | -7.3 ± 3.3 | -6.4 ± 3.2 |
EQ-5D-5L is a standardized measure of health status, provides a simple, generic measure of health for clinical and economic appraisal, and consists of 2 sections: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L VAS. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., 183 weeks) was reported in this outcome measure.
| score on a scale | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|
| Chinese Cohort: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels Score: Visual Analog Scale Score | 3.6 ± 1.3 | 1.2 ± 1.2 |
EQ-5D-5L: consists of 2 sections: EQ-5D-5L health state utility index (descriptive system) \& VAS. The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort \& anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, \& extreme problems. Response options are measured with 5-point Likert scale (for 5L version). The EQ-5D-5L responses are converted into single index utility score between 0 to 1, where higher score indicates better health state \& lower score indicate worse health state. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., 183 weeks) was reported in this outcome measure.
| score on a scale | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|
| Chinese Cohort: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels Score: Health Utility Index Value | -0.0 ± 0.0 | 0.0 ± 0.0 |
QLQ-BR23: disease-specific Health-related QOL assesses impact of breast cancer \& side effects of treatment. EORTC-QLQ-BR23 contains 23 items: multi-item scales \& single-item measures. 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) \& 4 scales related to symptoms of disease or treatment (arm symptoms, breast symptoms, systemic therapy side effects, \& upset by hair loss). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., 183 weeks) was reported in this outcome measure.
| score on a scale | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|
| Body image | -0.8 ± 2.4 | 0.2 ± 2.3 |
| Sexual functioning | -1.6 ± 1.3 | -3.6 ± 1.3 |
| Future perspective | 8.3 ± 3.2 | 5.1 ± 3.0 |
| Systemic therapy side effects | -0.5 ± 1.1 | 0.5 ± 1.0 |
| Breast symptoms | 0.8 ± 1.7 | 0.5 ± 1.6 |
| Arm symptoms | -0.4 ± 1.4 | -0.8 ± 1.4 |
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was a medically important event. TEAEs were defined as AEs that developed, worsened (according to the Investigator's opinion), or became serious during the on-treatment period.
| Participants | Physician Choice Endocrine Monotherapy (PCEM) - Main Cohort | Amcenestrant 400 mg - Main Cohort | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|---|---|
| Any TEAE | 113 | 118 | 22 | 33 |
| Any TESAE | 16 | 25 | 2 | 5 |
PFS is defined as the time in months interval from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) assessed by independent central review (ICR) or death (due to any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
| months | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort |
|---|---|---|
| Progression Free Survival (PFS) | 3.7 (2.0 to 4.9) | 3.6 (2.0 to 3.9) |
PFS is defined as the time in months interval from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by ICR or death (due to any cause), whichever comes first. PD as per RECIST 1.1: at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
| months | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|
| Chinese Cohort: Progression Free Survival | NA (3.7 to NA) | 7.2 (3.7 to NA) |
Collected over AEs and SAEs were collected from first dose of study treatment (Cycle 1 Day 1) up to 152 weeks for main cohort and 183 weeks for Chinese cohort. All-cause mortality (deaths) was collected from first dose of study drug (Day 1) to the end of follow-up for death for each participant, up to approximately 761 days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | 52/147 (35.4%) | 16/147 (10.9%) | 79/147 (53.7%) |
| Amcenestrant 400 mg- Main Cohort | 46/143 (32.2%) | 25/143 (17.5%) | 86/143 (60.1%) |
| Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | 2/42 (4.8%) | 2/42 (4.8%) | 14/42 (33.3%) |
| Amcenestrant- Chinese Cohort | 6/48 (12.5%) | 5/48 (10.4%) | 25/48 (52.1%) |
| Event | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant 400 mg- Main Cohort | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|---|---|
| Disease ProgressionGeneral disorders | 2/147 | 5/143 | 0/42 | 0/48 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 4/147 | 0/143 | 0/42 | 0/48 |
| Pleural EffusionRespiratory, thoracic and mediastinal disorders | 1/147 | 0/143 | 1/42 | 0/48 |
| Rib FractureInjury, poisoning and procedural complications | 0/147 | 0/143 | 1/42 | 0/48 |
| Pathological FractureMusculoskeletal and connective tissue disorders | 0/147 | 3/143 | 0/42 | 0/48 |
| Cancer PainNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/147 | 0/143 | 0/42 | 1/48 |
| HypertensionVascular disorders | 0/147 | 1/143 | 0/42 | 1/48 |
| Malignant Pleural EffusionRespiratory, thoracic and mediastinal disorders | 0/147 | 0/143 | 0/42 | 1/48 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 0/147 | 0/143 | 0/42 | 1/48 |
| Breast PainReproductive system and breast disorders | 0/147 | 1/143 | 0/42 | 1/48 |
| Event | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant 400 mg- Main Cohort | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort |
|---|---|---|---|---|
| NauseaGastrointestinal disorders | 13/147 | 28/143 | 1/42 | 3/48 |
| VomitingGastrointestinal disorders | 5/147 | 27/143 | 1/42 | 3/48 |
| CoughRespiratory, thoracic and mediastinal disorders | 8/147 | 7/143 | 6/42 | 6/48 |
| HeadacheNervous system disorders | 15/147 | 18/143 | 1/42 | 3/48 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 14/147 | 18/143 | 0/42 | 2/48 |
| Back PainMusculoskeletal and connective tissue disorders | 17/147 | 18/143 | 2/42 | 1/48 |
| FatigueGeneral disorders | 17/147 | 16/143 | 1/42 | 4/48 |
| ConstipationGastrointestinal disorders | 11/147 | 7/143 | 4/42 | 5/48 |
| DiarrhoeaGastrointestinal disorders | 9/147 | 14/143 | 1/42 | 1/48 |
| Hot FlushVascular disorders | 13/147 | 13/143 | 0/42 | 1/48 |
Analysis was performed on intent to treat (ITT) population which included all enrolled participants (i.e., who sign the informed consent form \[ICF\]) and for whom there is a confirmation of successful allocation of a randomization number by interactive response technology (IRT). 7 and 6 participants were included in PCEM-Chinese Cohort \& Amcenestrant-Chinese Cohort, respectively from the Main Cohort. Therefore, baseline measure data are reported for each cohort separately.
| Age, Continuous(years) | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort | Total |
|---|---|---|---|---|---|
| Main cohort | 59.2 ± 12.5 | 58.2 ± 11.8 | — | — | 58.7 ± 12.2 |
| Chinese cohort | — | — | 53.1 ± 10.7 | 55.2 ± 10.7 | 54.2 ± 10.7 |
| Sex: Female, Male(Participants) | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort | Total |
|---|---|---|---|---|---|
| Main cohort — Female | 146 | 143 | — | — | 289 |
| Main cohort — Male | 1 | 0 | — | — | 1 |
| Chinese cohort — Female | — | — | 42 | 47 | 89 |
| Chinese cohort — Male | — | — | 0 | 1 | 1 |
| Race (NIH/OMB)(Participants) | Physician Choice Endocrine Monotherapy (PCEM)- Main Cohort | Amcenestrant- Main Cohort | Physician Choice Endocrine Monotherapy (PCEM)- Chinese Cohort | Amcenestrant- Chinese Cohort | Total |
|---|---|---|---|---|---|
| Main cohort — American Indian or Alaska Native | 0 | 0 | — | — | 0 |
| Main cohort — Asian | 34 | 32 | — | — | 66 |
| Main cohort — Native Hawaiian or Other Pacific Islander | 2 | 0 | — | — | 2 |
| Main cohort — Black or African American | 0 | 0 | — | — | 0 |
| Main cohort — White | 102 | 102 | — | — | 204 |
| Main cohort — More than one race | 2 | 0 | — | — | 2 |
| Main cohort — Unknown or Not Reported | 7 | 9 | — | — | 16 |
| Chinese cohort — American Indian or Alaska Native | — | — | 0 | 0 | 0 |
| Chinese cohort — Asian | — | — | 42 | 48 | 90 |
| Chinese cohort — Native Hawaiian or Other Pacific Islander | — | — | 0 | 0 | 0 |
| Chinese cohort — Black or African American | — | — | 0 | 0 | 0 |
| Chinese cohort — White | — | — | 0 | 0 | 0 |
| Chinese cohort — More than one race | — | — | 0 | 0 | 0 |
| Chinese cohort — Unknown or Not Reported | — | — | 0 | 0 | 0 |
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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
This study is terminated, as verified in Feb 2026. You cannot join it, but the record below documents what was studied.
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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Sanofi