Phase 2 Study of Amcenestrant (SAR439859) Versus Physician's Choice in Locally Advanced or Metastatic ER-positive Breast Cancer (AMEERA-3)

An Open Label Randomized Phase 2 Trial of Amcenestrant (SAR439859), Versus Endocrine Monotherapy as Per Physician's Choice in Patients With Estrogen Receptor-positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer With Prior Exposure to Hormonal Therapies

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:

• To compare the overall survival in the 2 treatment arms
• To assess the objective response rate in the 2 treatment arms
• To evaluate the disease control rate in the 2 treatment arms
• To evaluate the clinical benefit rate in the 2 treatment arms
• To evaluate the duration of response in the 2 treatment arms
• To evaluate the PFS according to the estrogen receptor 1 gene (ESR1) mutation status in the 2 treatment arms
• To evaluate the pharmacokinetics of amcenestrant as single agent
• To evaluate health-related quality of life in the 2 treatment arms
• To compare the overall safety profile in the 2 treatment arms

Study Overview

• Status: Terminated
• Conditions: Breast Cancer Metastatic
• Intervention / Treatment: Drug: Amcenestrant; Drug: Fulvestrant; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Tamoxifen

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 367
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1426
    • Investigational Site Number : 0320001
  • Buenos Aires, Argentina, 1012
    • Investigational Site Number : 0320007
  • Buenos Aires, Argentina, 1019
    • Investigational Site Number : 0320008
  • Buenos Aires, Argentina, 1125
    • Investigational Site Number : 0320006
  • La Rioja, Argentina, 5300
    • Investigational Site Number : 0320004
  • Salta, Argentina, 4400
    • Investigational Site Number : 0320002
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, 2000
      • Investigational Site Number : 0320005
• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Investigational Site Number : 0360003
    • Woolloongabba, Queensland, Australia, 4102
      • Investigational Site Number : 0360002
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Investigational Site Number : 0360001
• Belgium
  • Charleroi, Belgium, 6000
    • Investigational Site Number : 0560002
  • Leuven, Belgium, 3000
    • Investigational Site Number : 0560001
  • Namur, Belgium, 5000
    • Investigational Site Number : 0560003
• Brazil
  • São Paulo, Brazil, 04014-002
    • IBCC - Núcleo de Pesquisa e Ensino- Site Number : 0760006
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-070
      • Associacao de Combate ao Cancer em Goias Hospital Araujo Jorge- Site Number : 0760005
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90880-480
      • Hospital Mae de Deus Site Number : 0760002
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre- Site Number : 0760001
  • São Paulo
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Fundação Faculdade Regional de Medicina de São José do Rio Preto- Site Number : 0760003
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Investigational Site Number : 1240004
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Investigational Site Number : 1240003
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Investigational Site Number : 1240006
• China
  • Beijing, China, 100021
    • Investigational Site Number : 1560001
  • Changchun, China, 130021
    • Investigational Site Number : 1560015
  • Changsha, China, 410005
    • Investigational Site Number : 1560014
  • Chengdu, China, 610041
    • Investigational Site Number : 1560025
  • Hangzhou, China, 310016
    • Investigational Site Number : 1560023
  • Hangzhou, China, 310022
    • Investigational Site Number : 1560002
  • Harbin, China, 150081
    • Investigational Site Number : 1560005
  • Hefei, China, 230001
    • Investigational Site Number : 1560010
  • Hefei, China, 230022
    • Investigational Site Number : 1560018
  • Jinan, China, 250013
    • Investigational Site Number : 1560026
  • Linyi, China, 276000
    • Investigational Site Number : 1560008
  • Nanjing, China, 210029
    • Investigational Site Number : 1560011
  • Tianjin, China, 300060
    • Investigational Site Number : 1560013
  • Wuhan, China, 430079
    • Investigational Site Number : 1560016
  • Xuzhou, China, 221018
    • Investigational Site Number : 1560031
  • Ürümqi, China, 830000
    • Investigational Site Number : 1560021
  • Maryland
    • Chongqing, Maryland, China, 400030
      • Investigational Site Number : 1560024
  • Michigan
    • Kunming, Michigan, China, 650106
      • Investigational Site Number : 1560003
• Czechia
  • Brno, Czechia, 656 53
    • Investigational Site Number : 2030002
  • Nový Jičín, Czechia, 741 01
    • Investigational Site Number : 2030003
  • Prague, Czechia, 140 59
    • Investigational Site Number : 2030004
• France
  • Angers, France, 49055
    • Investigational Site Number : 2500008
  • Créteil, France, 94010
    • Investigational Site Number : 2500006
  • Marseille, France, 13273
    • Investigational Site Number : 2500007
  • Paris, France, 75010
    • Investigational Site Number : 2500005
  • Villejuif, France, 94805
    • Investigational Site Number : 2500001
• Greece
  • Heraklion, Greece, 711 10
    • Investigational Site Number : 3000001
  • Larissa, Greece, 411 10
    • Investigational Site Number : 3000002
  • Quebec
    • Thessaloniki, Quebec, Greece, 546 45
      • Investigational Site Number : 3000004
• Israel
  • Jerusalem, Israel, 9103102
    • Investigational Site Number : 3760002
  • Petah Tikva, Israel, 4941492
    • Investigational Site Number : 3760001
  • Ramat Gan, Israel, 5262100
    • Investigational Site Number : 3760004
  • Tel Aviv, Israel, 6423906
    • Investigational Site Number : 3760003
• Italy
  • Prato, Italy, 59100
    • Investigational Site Number : 3800003
  • Milano
    • Milan, Milano, Italy, 20141
      • Investigational Site Number : 3800002
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Investigational Site Number : 3800001
• Japan
  • Osaka, Japan, 540-0006
    • Investigational Site Number : 3920003
  • Tokyo, Japan, 135-8550
    • Investigational Site Number : 3920008
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Investigational Site Number : 3920002
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Investigational Site Number : 3920001
  • Gunma
    • Ōta, Gunma, Japan, 373-8550
      • Investigational Site Number : 3920009
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-0815
      • Investigational Site Number : 3920006
  • Nagano
    • Ina, Nagano, Japan, 362-0806
      • Investigational Site Number : 3920005
  • Tokyo
    • Chūō, Tokyo, Japan, 104-0045
      • Investigational Site Number : 3920004
• Latvia
  • Riga, Latvia, LV-1002
    • Investigational Site Number : 4280002
  • Riga, Latvia, LV-1038
    • Investigational Site Number : 4280001
• Mexico
  • Mexico City, Mexico, 03100
    • Investigational Site Number : 4840005
  • Veracruz, Mexico, 91900
    • Investigational Site Number : 4840006
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Investigational Site Number : 4840002
• Poland
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 61-866
      • Investigational Site Number : 6160003
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Investigational Site Number : 6160001
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Hospital Auxilio Mutuo- Site Number : 8400028
• Russia
  • Moscow, Russia, 105005
    • Investigational Site Number : 6430005
  • Moscow, Russia, 115478
    • Investigational Site Number : 6430003
  • Georgia
    • Saint Petersburg, Georgia, Russia, 197758
      • Investigational Site Number : 6430002
• South Korea
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, South Korea, 03080
      • Investigational Site Number : 4100001
    • Seoul, Seoul-teukbyeolsi, South Korea, 03722
      • Investigational Site Number : 4100004
    • Seoul, Seoul-teukbyeolsi, South Korea, 06351
      • Investigational Site Number : 4100002
    • Seoul, Seoul-teukbyeolsi, South Korea, 05505
      • Investigational Site Number : 4100003
• Spain
  • Málaga, Spain, 29010
    • Investigational Site Number : 7240008
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number : 7240006
  • Catalunya [Cataluña]
    • Barcelona, Catalunya [Cataluña], Spain, 08036
      • Investigational Site Number : 7240003
    • L'Hospitalet de Llobregat, Catalunya [Cataluña], Spain, 08907
      • Investigational Site Number : 7240001
• Taiwan
  • Taichung, Taiwan, 404
    • Investigational Site Number : 1580002
  • Tainan, Taiwan, 704
    • Investigational Site Number : 1580003
  • Taipei, Taiwan, 100
    • Investigational Site Number : 1580001
  • Taipei, Taiwan, 104
    • Investigational Site Number : 1580005
  • Taipei, Taiwan, 114
    • Investigational Site Number : 1580004
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06200
    • Investigational Site Number : 7920004
  • Edirne, Turkey (Türkiye), 22030
    • Investigational Site Number : 7920002
  • Istanbul, Turkey (Türkiye), 34722
    • Investigational Site Number : 7920003
• Ukraine
  • Kryvyi Rih, Ukraine, 50048
    • Investigational Site Number : 8040001
  • Odesa, Ukraine, 65025
    • Investigational Site Number : 8040004
  • Uzhhorod, Ukraine, 88000
    • Investigational Site Number : 8040005
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Alabama Oncology - St. Vincent's Birmingham- Site Number : 8400008
  • California
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood and Cancer Center Site Number : 8400018
    • Santa Monica, California, United States, 90404
      • UCLA Santa Monica - Parkside- Site Number : 8400024
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Clinical Research Center- Site Number : 8400027
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Hematology Oncology Clinic Site Number : 8400020
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute- Site Number : 8400015
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City- Site Number : 8400032
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center - Lebanon - 1 Medical Center Drive- Site Number : 8400013
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Meridian Health - Hackensack University Medical Center- Site Number : 8400025
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center- Site Number : 8400006
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer & Blood Disorders - Fort Worth- Site Number : 8400022
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center- Site Number : 8400026
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties Tacoma- Site Number : 8400038
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospitals and Clinics- Site Number : 8400016

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria :

• 18 years or older.
• Histological or cytological diagnosis of adenocarcinoma of the breast.
• Locally advanced not amenable to radiation therapy or surgery in a curative intent, and/or metastatic disease.
• Estrogen receptor(ER) positive status.
• Human epidermal growth factor receptor 2 negative status.
• Participants must have received no more than 1 prior chemotherapeutic or 1 targeted therapy regimen for advanced/metastatic disease.
• In the main study, a prior treatment with a Cyclin-dependent kinase 4 and 6(CDK 4/6) inhibitor is mandatory if this treatment is approved and can be reimbursed for this participant. The percentage of participants without previous CDK 4/6 inhibitor will be capped to 20%. In the Chinese extension cohort, previous treatment with a CDK 4/6 inhibitor will not be mandatory, and there will be no limitation to the number of participants naïve to CDK4/6 inhibitor.
• Participants must present a secondary endocrine resistance to endocrine therapy defined as: progression while on endocrine therapy after at least 6 months of treatment for advanced breast cancer, or relapse while on adjuvant endocrine therapy but after the first 2 years, or with a relapse within 12 months after completing adjuvant endocrine therapy.
• Male or Female.

Exclusion criteria:

• Eastern Cooperative Oncology Group performance status =>2.
• Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of amcenestrant. Participants unable to swallow normally and to take capsules.
• Participant with any other cancer. Adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or any other cancer from which the participant has been disease free for greater than 3 years are allowed.
• Severe uncontrolled systemic disease at screening .
• Participants with known brain metastases that are untreated, symptomatic or require therapy to control symptoms.
• Prior treatment with mammalian target of rapamycin inhibitors or any other selective estrogen receptor degrader(SERD) compound, except fulvestrant if stopped for at least 3 months before randomization.
• Treatment with drugs that have the potential to inhibit Uridine'5 Diphospho-Glucuronosyl Transferase(UGT) less than 2 weeks before randomization.
• Treatment with strong Cytochrome P450 (CYP)3A inducers within 2 weeks before randomization.
• Ongoing treatment with drugs that are sensitive substrate of organic anion transporting polypeptide 1B1/B3(OATP1B1/B3) (asunaprevir, atorvastatin, bosentan, danoprevir, fexofenadine, glyburide, nateglinide, pitavastatin, pravastatin, replaglinide, rosuvastatin, and simvastatin acid).
• Treatment with anticancer agents (including investigational drugs) less than 3 weeks before randomization.
• Inadequate hematological, coagulation, renal and liver functions.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amcenestrant; Daily amcenestrant dose administered orally under fed or fast condition	Drug: Amcenestrant; Pharmaceutical form: Capsule Route of administration: Oral
Active Comparator: Fulvestrant/Aromatase inhibitors/Estrogen receptor modulator; 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; Pharmaceutical form: Solution for injection Route of administration: Intramuscular; Other Names: Faslodex®; Drug: Anastrozole; Pharmaceutical form:Tablets or capsules Route of administration: Oral; Other Names: Arimidex®/Anastrozole Generics; Drug: Letrozole; Pharmaceutical form: Tablets or capsules Route of administration: Oral; Other Names: Femara®/Letrozole Generics; Drug: Exemestane; Pharmaceutical form: Tablets or capsules Route of administration: Oral; Other Names: Aromasin®/Exemestane Generics; Drug: Tamoxifen; Pharmaceutical form: Tablets or capsules Route of administration: Oral; Other Names: Nolvadex®/Tamoxifen Generics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	From first dose of study treatment (Cycle 1 Day 1) up to 152 weeks for main cohort and 183 weeks for Chinese cohort

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

General Publications

• Tolaney SM, Chan A, Petrakova K, Delaloge S, Campone M, Iwata H, Peddi PF, Kaufman PA, De Kermadec E, Liu Q, Cohen P, Paux G, Wang L, Ternes N, Boitier E, Im SA. AMEERA-3: Randomized Phase II Study of Amcenestrant (Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Monotherapy in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. J Clin Oncol. 2023 Aug 20;41(24):4014-4024. doi: 10.1200/JCO.22.02746. Epub 2023 Jun 22.

Helpful Links

• ACT16105 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2019
• Primary Completion (Actual): February 15, 2022
• Study Completion (Actual): January 2, 2025

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: August 15, 2019
• First Posted (Actual): August 16, 2019

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Benzene Derivatives; Nitriles; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Triazoles; Stilbenes; Benzylidene Compounds; Letrozole; Fulvestrant; Anastrozole; Tamoxifen; exemestane
• Other Study ID Numbers: ACT16105 (Sanofi Identifier); 2018-004593-98 (EudraCT Number); U1111-1217-2774 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No