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Breast CancerPhase 1/2AMEERA-1NCT03284957

Phase 1/2 Study of Amcenestrant (SAR439859) Single Agent and in Combination With Other Anti-cancer Therapies in Postmenopausal Women With Estrogen Receptor Positive Advanced Breast Cancer

A Phase 1/2 study testing Amcenestrant, Palbociclib and Alpelisib in people with Breast Cancer, run by Sanofi at 25 sites in 10 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Primary Objectives: Dose Escalation: To assess the incidence rate of dose-limiting toxicity (DLT) and to determine the maximum tolerated dose (MTD) as well as the recommended dose (RD) of amcenestrant administered as monotherapy and in combination with palbociclib To assess the incidence rate of DLT and determine the… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Amcenestrant, Palbociclib and Alpelisib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
136 participants
Where
25 sitesin 10 countries
Study dates
20 Sep 2017to 8 Nov 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must be postmenopausal women
  • Histological diagnosis of breast adenocarcinoma
  • Locally advanced or metastatic disease
  • Either primary tumor or any metastatic site to be positive for Estrogen Receptors (ER+) and negative for HER2 (HER2-) receptor
  • Participants must have been previously treated with at least 6 months of endocrine therapy for advanced disease:
  • Dose Escalation study parts:
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  • Arm #3 - Part F and Arm #5 - Part J: up to 2 prior lines of either single endocrine therapy and/or endocrine-based therapy Arm #4 -H: up to 2 prior lines of either single endocrine therapy and/or endocrine-based therapy (exemestane not allowed)
  • Dose Expansion study parts: Arm #2: - Part D: no more than 2 prior lines of advanced endocrine therapy for advanced disease are allowed Arm #3, - Part G: patients must have received and progressed on the combination of Aromatase Inhibitors (AI) + CDK4/6 inhibitor as the first line (1L) treatment for advanced disease Arm #4 - Part I: participants must have received and progressed on the combination of Aromatase Inhibitors (AI) +CDK4/6 Inhibitor as the first line (1L) treatment for advanced disease (exemestane not allowed) Arm#5: - Part K: up to 1 prior line of a single endocrine therapy for advanced disease Note: Additional patients who relapsed while on previous adjuvant endocrine therapy that was initiated ≥24 months ago, or relapsed < 12 months after completion of adjuvant endocrine therapy are also allowed for Arms #2, #3, #4, and #5 (Parts C, D, F, G, H, I, J and K).
  • Participants previously treated with chemotherapy for advanced disease: no more than 3 prior chemotherapeutic regimens in Arm #1 Part A, and no more than 1 prior chemotherapeutic regimen in Arms #1, #2, #3, #4, and #5 (Parts B, C, D, F, H and J respectively); prior chemotherapy for advanced disease is not allowed in dose expansion of Arms #3, #4, and #5 (Part G, I and K respectively).
  • Measurable lesion

Who cannot join

  • Medical history or ongoing gastrointestinal disorders that could affect absorption of oral study drugs (including difficulties with swallowing capsules)
  • Participants with any other cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or any other cancer from which the participant has been disease free for >3 years)
  • Participants with known brain metastases
  • Treatment with anticancer agents (including investigational drugs) less than 2 weeks before first study treatment starts (less than 4 weeks if the anticancer agents were antibodies)
  • Prior treatment with another selective ER down-regulator (SERD)
  • Dose Escalation study parts (Parts F, H and J): SERDs are not allowed except for fulvestrant which will need a washout of at least 6 weeks prior to the first study drug administration
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  • Dose Expansion study parts (Parts G, I and K): prior (last) treatment with any SERD including fulvestrant will not be allowed
  • Inadequate hematological and biochemical lab tests
  • Participants with Gilbert disease
  • Treatment with HIV-antiviral, antifungal and antioxidant agents less than 2 weeks before study treatment starts
  • Treatment with strong P450 (CYP) 3A inducers within 2 weeks before first study treatment
  • Treatment with OATP1B1/B3 sensitive substrates and which cannot be replaced
  • Arm#2 Treatment with strong CYP3A inhibitors within 2 weeks before first study treatment starts
  • More than one prior advanced cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapy in Arm #1, Arm #2 (Part C), Arm #3 (Parts F and G), and Arm#4 (Part H).
  • Arm #2, #3, #4 and #5 (Parts C, D, F, G, H, I, J and K) only: participants with concurrent or history of pneumonitis
  • Arm #3, #4 and #5 (Parts F, G, H, I, J and K) only: prior treatment therapies that target the PI3K axis (mTOR inhibitors, AKT inhibitors, PI3K inhibitors)
  • Arm #3 and #4 (Parts F, G, H and I) only: participants with diabetes mellitus type-I or uncontrolled diabetes mellitus type-II: ie, fasting plasma glucose ≥ 140mg/dl (7.7 mmol/l) or HbA1C > 6.2%
  • Arm #3 and #4 (Parts F, G, H and I) only: history of severe cutaneous reaction (eg. Stevens-Johnson syndrome [SJS], erythema multiforme [EM]), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms [DRESS].
  • Arm #3 (Parts F and G) only: ongoing osteonecrosis of jaw
  • Arm #4 (Parts H and I) only: any active, untreated or uncontrolled infection (e.g. viral, bacterial, fungal etc.)
  • Arm #4 (Parts H and I) only: participants with active and uncontrolled stomatitis, angioedema due to concomitant treatment with ACE inhibitors, impaired wounds
  • Arm #4 (Parts H and I) only: uncontrolled hypercholesterolemia, hypertriglyceridemia and hyperglycemia in non-diabetic participants
  • Arm #4 (Parts H and I) only: treatment with strong or moderate CYP3A4 inhibitors, strong CYP3A4 inducers and/or P-gp inhibitors within 2 weeks before the first study treatment administration or 5 elimination half-lives, whichever is the longest
  • Arm #5 (Parts J and K) only: history or current (controlled/not controlled) venous thromboembolism (i.e. deep vein thrombosis (DVT), pulmonary embolism (PE), cerebral venous sinus thrombosis (CVST)
  • The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial locations and contacts

25 sites in 10 countries.

25 sites in 10 countries

France5 sites

  • Investigational Site Number : 2500002

    Bordeaux, 33076

  • Investigational Site Number : 2500005

    Lille, 59000

  • Investigational Site Number : 2500003

    Lyon, 69373

  • Investigational Site Number : 2500001

    Saint-Herblain, 44805

  • Investigational Site Number : 2500004

    Villejuif, 94805

Other trials in France

United States4 sites

  • University of Colorado - Anschutz Medical Campus- Site Number : 8400005

    Aurora, Colorado, 80045

  • Massachusetts General Hospital- Site Number : 8400002

    Boston, Massachusetts, 02114

  • Memorial Sloan Kettering Cancer Center - New York - York Avenue- Site Number : 8400003

    New York, New York, 10065

  • Fred Hutchinson Cancer Center- Site Number : 8400001

    Seattle, Washington, 98109

Other trials in United States

Canada3 sites

  • Investigational Site Number : 1240004

    Edmonton, Alberta, T6G 1Z2

  • Investigational Site Number : 1240002

    Toronto, Ontario, M4N 3M5

  • Investigational Site Number : 1240003

    Vancouver, British Columbia, V5Z 1L3

Other trials in Canada

Czechia3 sites

  • Investigational Site Number : 2030002

    Brno, 656 53

  • Investigational Site Number : 2030001

    Prague, 128 08

  • Investigational Site Number : 2030003

    Prague, 140 59

Other trials in Czechia

Spain3 sites

  • Investigational Site Number : 7240007

    Madrid, 28034

  • Investigational Site Number : 7240001

    Madrid, 28041

  • Investigational Site Number : 7240002

    Madrid, 28050

Other trials in Spain

Portugal2 sites

  • Investigational Site Number : 6200001

    Lisbon, 1649-035

  • Investigational Site Number : 6200002

    Lisbon, 1998-018

Other trials in Portugal

United Kingdom2 sites

  • Investigational Site Number : 8260002

    Cardiff, Cardiff [Caerdydd Gb-crd], CF14 2TL

  • Investigational Site Number : 8260003

    Oxford, Oxfordshire, OX3 7LE

Other trials in United Kingdom

Belgium1 site

  • Investigational Site Number : 0560001

    Leuven, 3000

Other trials in Belgium

Italy1 site

  • Investigational Site Number : 3800003

    Milan, Milano, 20141

Other trials in Italy

Poland1 site

  • Investigational Site Number : 6160004

    Gdynia, Pomeranian Voivodeship, 81-519

Other trials in Poland

About this study

Official title: A Phase 1/2 Study for the Safety, Efficacy, Pharmacokinetic and Pharmacodynamics Evaluation of Amcenestrant (SAR439859), Administered Orally as Monotherapy, Then in Combination With Other Anti-cancer Therapies in Postmenopausal Women With Estrogen Receptor-positive Advanced Breast Cancer

Primary Objectives:

Dose Escalation:

Read more
  • To assess the incidence rate of dose-limiting toxicity (DLT) and to determine the maximum tolerated dose (MTD) as well as the recommended dose (RD) of amcenestrant administered as monotherapy and in combination with palbociclib
  • To assess the incidence rate of DLT and determine the RD of everolimus or abemaciclib in combination with the selected amcenestrant dose for the combination therapy

Safety Run-In:

  • To confirm the RD of amcenestrant in combination with alpelisib

Dose Expansion:

  • Antitumor activity using objective response rate (ORR)
  • Overall safety profile of amcenestrant administered in combination with palbociclib, alpelisib, everolimus, and abemaciclib

Secondary Objectives:

  • Overall safety profile of amcenestrant monotherapy and in combination
  • Pharmacokinetic (PK) profile of amcenestrant administered as monotherapy or in combination and PK profile of palbociclib, alpelisib, everolimus and abemaciclib
  • Antitumor activity using ORR, the clinical benefit rate (CBR) and progression free survival (PFS)
  • Time to first tumor response
  • Residual ER availability with positron emission tomography (PET) scan [(18)F] fluoroestradiol (18F-FES) uptake with increasing doses of amcenestrant
  • Food effect on PK of amcenestrant
  • Potential induction/inhibition effect of amcenestrant on cytochrome P450 (CYP) 3A using 4b-OH cholesterol
Read the detailed description

Duration of the study, per participant, will include eligibility period (screening period) of up to 4 weeks (28 days), treatment period (at least 1 cycle [28 days] of study treatment), and end of treatment (EOT) visit at least 22 to 30 days (or until the participant receives another anticancer therapy, whichever is earlier) following the last study treatment administration. The expected enrollment period is approximately 60 months.

Conditions
Breast Cancer
Being tested
Amcenestrant, Palbociclib, Alpelisib, Everolimus, Abemaciclib
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AmcenestrantDrug

    Also called SAR439859

    Pharmaceutical form: capsule

    Route of administration: oral

  • PalbociclibDrug

    Also called Ibrance®

    Pharmaceutical form: capsule

    Route of administration: oral

  • AlpelisibDrug

    Also called Piqray®

    Pharmaceutical form: tablet

    Route of administration: oral

  • EverolimusDrug

    Pharmaceutical form: tablet

  • AbemaciclibDrug

    Also called Verzenio®

    Pharmaceutical form: tablet

Study groups in NCT03284957
Study groupRoleWhat they receive
Amcenestrant Monotherapy: Arm #1 Part A Dose Escalation, Part B Dose ExpansionExperimentalPart A: Amcenestrant will be administered orally once daily (QD). Treatment will begin with an identified starting dose. Administration of higher doses to subsequent participants is based on occurrence of DLTs and evaluation of target saturation and PK parameters at initial and subsequent doses, until maximum administered dose (MAD) is reached. Drug will be administered in a 28-day cycle. Part B: When the dose escalation phase ends, the recommended dose will be administered for the expansion cohort. Drug will be administered in a 28-day cycle.
Receives: Drug: Amcenestrant
Amcenestrant/Palbociclib: Arm #2 Part C Dose Escalation, Part D Dose ExpansionExperimentalPart C: Amcenestrant will be administered in combination with palbociclib: amcenestrant starting oral daily dose will be one dose level below monotherapy RD and palbociclib will be dosed at fixed standard dose. Administration of higher dose of amcenestrant (with standard palbociclib dose) to subsequent participants will be based on occurrence of DLTs at initial and subsequent doses, until MAD of amcenestrant is reached. Drugs will be administered in a 28-day cycle (palbociclib will be administered for 21 days of cycle). Part D: Based on the results in Part C, participants will be administered either: 1) a determined amcenestrant dose (RD) with standard dose of palbociclib in combination therapy, or 2) one of two randomized dose levels of amcenestrant with standard dose of palbociclib in combination therapy. Drugs will be administered in a 28-day cycle (palbociclib will be administered for 21 days of cycle).
Receives: Drug: Amcenestrant; Drug: Palbociclib
Amcenestrant/Alpelisib: Arm #3 Part F Safety Run-In, Part G Dose ExpansionExperimentalPart F: Amcenestrant will be administered in combination with alpelisib at a fixed standard dose. Additional dose levels of amcenestrant with alpelisib could be explored if needed based on the safety and PK results. Lower dose of alpelisib could be explored based on the PK results and safety profile from the initial combination administration. Both amcenestrant and alpelisib will be administered in a 28-day cycle. Part G: Based on the conclusion in Part F, participants will be administered the determined RD of amcenestrant and alpelisib given in the combination in an expansion cohort. Both study drugs will be administered in a 28-day cycle.
Receives: Drug: Amcenestrant; Drug: Alpelisib
Amcenestrant/Everolimus: Arm #4 Part H Dose Escalation, Part I Dose ExpansionExperimentalPart H: Amcenestrant will be administered at the determined RD in combination with 2 dose levels of everolimus. Additional dose levels of amcenestrant with everolimus could be explored if needed based on the safety and PK results. Both amcenestrant and everolimus will be administered in a 28-day cycle. Part I: Based on the conclusion in Part H, participants will be administered the determined RD of amcenestrant and RD of everolimus given in the combination in an expansion cohort. Both study drugs will be administered in a 28-day cycle.
Receives: Drug: Amcenestrant; Drug: Everolimus
Amcenestrant/Abemaciclib: Arm #5 Part J Dose Escalation, Part K Dose ExpansionExperimentalPart J: Amcenestrant will be administered at the determined RD in combination with 2 dose levels of abemaciclib. Additional dose levels of amcenestrant with abemaciclib could be explored if needed based on the safety and PK results. Both amcenestrant and abemaciclib will be administered in a 28-day cycle. Part K: Based on the conclusion in Part J, participants will be administered the determined RD of amcenestrant and RD of abemaciclib given in the combination in an expansion cohort. Both study drugs will be administered in a 28-day cycle.
Receives: Drug: Amcenestrant; Drug: Abemaciclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Parts A, C, F, H, J: Number of Participants With Study Treatment-Related Dose-Limiting Toxicities (DLTs)

    DLTs: any treatment-emergent adverse event(TEAE) related to study treatment per National Cancer Institute Common Terminology Criteria for AE scale version (v) 4.03:Grade(G)≥3 nonhematological toxicity except:G3 nausea/vomiting resolved to G≤1 in 48 hours(h),G3 diarrhea with therapy and lasting<48h,G3 hyperglycemia resolved to G≤1 in 48h(Part H);G≥3 hematological toxicity except:G3 anemia,G4 neutropenia<7days(d),G3 neutropenia without fever/infection,G3 thrombocytopenia without bleeding;elevated total serum bilirubin(BL)>2xupper limit of normal(except Part F),Part F:G3 hyperglycemia not resolved to G≤2 in 7d after antidiabetic treatment,G2 hyperglycemia not resolved to G≤1 in 21d,G2 alanine aminotransferase(ALT) increase in conjunction with total blood BL G≥2 without liver metastases,G≥3 ALT/aspartate aminotransferase increase for>4d,G3 rash/maculopapular rash not resolved to G≤1 in 7d;treatment related toxicity causing≥7d omission in Cycle 1 or >2 weeks delay in Cycle 2 in Part C.

    Measured: Cycle 1 Day 1 to Cycle 1 Day 28 (cycle duration=28 days)

  2. Part B: Objective Response Rate (ORR) as Determined by Independent Central Review (ICR)

    ORR was determined by dividing the number of participants who achieved confirmed complete response (CR) or partial response (PR) by the number of participants from the analysis population. ORR was assessed by ICR according to response evaluation criteria in solid tumors (RECIST) v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 278 weeks

  3. Parts D, I: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs)

    AE was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which did not necessarily had a causal relationship with the treatment. SAE was any untoward medical occurrence that at any dose, resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed or worsened or became serious during the treatment period.

    Measured: From first dose of study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration; approximately 232 weeks for Part D and 11 weeks for Part I

Secondary outcomes (37)

  1. Parts A, B, C, F, H, J: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events

    AE was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which did not necessarily had a causal relationship with the treatment. SAE was any untoward medical occurrence that at any dose, resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed or worsened or became serious during the treatment period.

    Measured: From first dose of study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration; approximately 94, 282, 144, 96, 59, 130 weeks for Parts A, B, C, F, H, J respectively

  2. Parts A, B, C, D, F, H, I, J: Objective Response Rate as Determined by Investigators/Local Radiologists

    ORR was determined by dividing the number of participants who achieved confirmed CR or PR by the number of participants from the analysis population. ORR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228, 92, 55, 7, 126 weeks for Parts A, B, C, D, F, H, I, J respectively

  3. Parts A, B, C, D, F, H, I, J: Clinical Benefit Rate (CBR) as Determined by Investigators/Local Radiologists

    CBR was determined by dividing the number of participants who achieved confirmed CR, PR as best overall response (BOR) or stable disease (SD) for ≥24 weeks by the number of participants from the analysis population. CBR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study.

    Measured: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228, 92, 55, 7, 126 weeks for Parts A, B, C, D, F, H, I, J respectively

  4. Part B: Clinical Benefit Rate as Determined by Independent Central Review

    CBR was determined by dividing the number of participants who achieved confirmed CR, PR as BOR or SD for ≥24 weeks by the number of participants from the analysis population. CBR was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

    Measured: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 278 weeks

  5. Parts A, B, C, D, F, H, I, J: Duration of Response (DOR) as Determined by Investigators/Local Radiologists

    DOR was defined as the time interval from the date of the first occurrence of confirmed CR or PR to the date of the first documentation of disease progression or death due to disease progression, whichever occurred first. DOR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, an absolute increase of at least 5 mm in the sum. Appearance of 1 or more new lesions was also considered progression.

    Measured: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228, 92, 55, 7, 126 weeks for Parts A, B, C, D, F, H, I, J respectively

  6. Part B: Duration of Response as Determined by Independent Central Review

    DOR was defined as the time interval from the date of the first occurrence of confirmed CR or PR to the date of the first documentation of disease progression or death due to disease progression, whichever occurred first. DOR was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, an absolute increase of at least 5 mm in the sum. Appearance of 1 or more new lesions was also considered progression.

    Measured: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 278 weeks

  7. Parts A, B, C, D, F, H, I, J: Progression-Free Survival (PFS) as Determined by Investigators/Local Radiologists

    PFS was defined as time from the date of the first treatment intake to the date of the first documentation of objective PD according to RECIST v1.1, clinical PD or death due to any cause, whichever occurred first. PFS was assessed by investigators/local radiologists. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, an absolute increase of at least 5 mm in the sum. Appearance of 1 or more new lesions was also considered progression.

    Measured: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228, 92, 55, 7, 126 weeks for Parts A, B, C, D, F, H, I, J respectively

  8. Parts A, B, C, D: Objective Response Rate as Determined by Investigators/Local Radiologists According to Estrogen Receptor 1 (ESR1) Mutation at Baseline

    ORR was determined by dividing the number of participants who achieved confirmed CR or PR by the number of participants from the analysis population. ORR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The ESR1 gene mutation status (mutated or wild-type) was analyzed by multiplex droplet digital polymerase chain reaction (ddPCR) after extraction of plasma circulating deoxyribonucleic acid (DNA). The baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.

    Measured: From Baseline (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228 weeks for Parts A, B, C, D respectively

  9. Part B: Objective Response Rate as Determined by Independent Central Review According to Estrogen Receptor 1 Mutation at Baseline

    ORR was determined by dividing the number of participants who achieved confirmed CR or PR by the number of participants from the analysis population. ORR was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The ESR1 gene mutation status (mutated or wild-type) was analyzed by multiplex ddPCR after extraction of plasma circulating DNA. The baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.

    Measured: Baseline (Day 1) up to maximum exposure of study treatment; approximately 278 weeks

  10. Parts A, B, C, D: Clinical Benefit Rate as Determined by Investigators/Local Radiologists According to Estrogen Receptor 1 Mutation at Baseline

    CBR was determined by dividing the number of participants who achieved confirmed CR, PR as BOR or SD for ≥24 weeks by the number of participants from analysis population. CBR was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The ESR1 gene mutation status (mutated or wild-type) was analyzed by multiplex ddPCR after extraction of plasma circulating DNA. Baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.

    Measured: From Baseline (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228 weeks for Parts A, B, C, D respectively

  11. Parts B, D, I: Time to First Confirmed Response as Determined by Investigators/Local Radiologists

    The time to first confirmed response was defined as the time interval from the date of first administration of the study treatment to the date of the first occurrence of confirmed CR or PR. The time to first confirmed response was assessed by investigators/local radiologists according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 90, 278, 140, 228, 92, 55, 7, 126 weeks for Parts A, B, C, D, F, H, I, J respectively

  12. Part B: Time to First Confirmed Response as Determined by Independent Central Review

    The time to first confirmed response was defined as the time interval from the date of first administration of the study treatment to the date of the first occurrence of confirmed CR or PR. The time to first confirmed response was assessed by ICR according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 278 weeks

  13. Part A: Number of Participants With 18F-Fluorestradiol Positron Emission Tomography Percentage Reduction

    Inhibition of estrogen receptor (ER) occupancy investigation using 18F-FES-PET imaging was a limited invasive procedure that allowed assessment of ER presence by assessing the binding of radiolabeled estradiol, the ligand of ER (signal extinction). Number of participants with percentage reduction (≥90%, ≥70%, ≥50% and ≥30%) in 18F-FES-PET signal are reported. The baseline value was defined as the last value or measurement taken up to the date and time of the first dose of study treatment irrespective of the treatment.

    Measured: Baseline (within 3 days or more prior to Day 1) and between Day 11 and Day 15 of Cycle 1 (cycle duration=28 days)

  14. Parts A, B, C, D, H, I, J: Time Interval Between Administration and the Sampling Preceding the First Concentration Above the Lower Limit of Quantification (LLOQ) (Tlag) of Amcenestrant After a Single Oral Administration

    Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. Pharmacokinetic (PK) parameters were determined by non-compartmental analysis. LLOQ value for amcenestrant was 5 nanograms per milliliter (ng/mL).

    Measured: Cycle 1 Day 1 (cycle duration=28 days)

  15. Parts A, B, C, D, H, I, J: Time to Reach Maximum Plasma Concentration (Tmax) of Amcenestrant After a Single Oral Administration

    Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.

    Measured: Cycle 1 Day 1 (cycle duration=28 days)

  16. Parts A, B, C, D, H, I, J: Maximum Plasma Concentration (Cmax) of Amcenestrant After a Single Oral Administration

    Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.

    Measured: Cycle 1 Day 1 (cycle duration=28 days)

  17. Parts A, B, C, D, H, I, J: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Dosing Interval (AUC0-tau) of Amcenestrant After a Single Oral Administration

    Blood samples were collected at the specified timepoint for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis. tau=12 h for Part A BID dosing and 24 h for other parts.

    Measured: Cycle 1 Day 1 (cycle duration=28 days)

  18. Parts A, B, C, D, F, H, I, J: Time to Reach Maximum Plasma Concentration of Amcenestrant After Repeated Oral Administrations

    Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.

    Measured: Parts A, B, F, H, I, J: Cycle 1 Day 22; Parts C and D: Cycle 1 Day 21 (cycle duration=28 days)

  19. Parts A, B, C, D, F, H, I, J: Maximum Plasma Concentration of Amcenestrant After Repeated Oral Administrations

    Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis.

    Measured: Parts A, B, F, H, I, J: Cycle 1 Day 22; Parts C and D: Cycle 1 Day 21 (cycle duration=28 days)

  20. Parts A, B, C, D, F, H, I, J: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Dosing Interval of Amcenestrant After Repeated Oral Administrations

    Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations. PK parameters were determined by non-compartmental analysis. tau=12 h for Part A BID dosing and 24 h for other parts.

    Measured: Parts A, B, F, H, I, J: Cycle 1 Day 22; Parts C and D: Cycle 1 Day 21 (cycle duration=28 days)

  21. Parts A, B, C, D, F, H, I, J: Plasma Concentration Observed Before Treatment Administration (Ctrough) of Amcenestrant

    Blood samples were collected at the specified timepoints for the measurement of amcenestrant concentrations.

    Measured: Cycle 1: Pre-dose (0 hour) on Day 8 (Parts A, B, C, D), Day 15 (Parts B, C, D), Day 21 (Parts C and D) and Day 22 (Parts A, B, F, H, I, J) (cycle duration=28 days)

  22. Part B: Cumulated Amount of Amcenestrant Excreted in Urine From Time 0 to 24 Hours (Ae0-24)

    Urine samples were collected at the specified timepoints for the measurement of amcenestrant amount excreted in urine.

    Measured: Day 22 of Cycle 1 (cycle duration=28 days)

  23. Part A (QD Regimen): Geometric Mean Ratio of Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24) of Amcenestrant

    The food effect was assessed by comparing the geometric means of AUC0-24 between Cycle 1 Day 1 (fasted condition) and Cycle 1 Day 3 (fed condition) in Part A.

    Measured: Days 1 and 3 of Cycle 1 (cycle duration=28 days)

  24. Part A (QD Regimen): Geometric Mean Ratio of Maximum Plasma Concentration of Amcenestrant

    The food effect was assessed by comparing the geometric means of Cmax between Cycle 1 Day 1 (fasted condition) and Cycle 1 Day 3 (fed condition) in Part A.

    Measured: Days 1 and 3 of Cycle 1 (cycle duration=28 days)

  25. Parts C and D: Time to Reach Maximum Plasma Concentration of Palbociclib After First Dose and Repeated Oral Administrations in Combination With Amcenestrant

    Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 21) of palbociclib in combination with amcenestrant for the measurement of palbociclib concentrations. PK parameters were determined by non-compartmental analysis.

    Measured: Days 1 and 21 of Cycle 1 (cycle duration=28 days)

  26. Parts C and D: Maximum Plasma Concentration of Palbociclib After First Dose and Repeated Oral Administrations in Combination With Amcenestrant

    Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 21) of palbociclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.

    Measured: Days 1 and 21 of Cycle 1 (cycle duration=28 days)

  27. Parts C and D: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours of Palbociclib After First Dose and Repeated Oral Administrations in Combination With Amcenestrant

    Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 21) of palbociclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.

    Measured: Days 1 and 21 of Cycle 1 (cycle duration=28 days)

  28. Part F: Time to Reach Maximum Plasma Concentration of Alpelisib After Repeated Oral Administrations Alone or in Combination With Amcenestrant

    Blood samples were collected after 3-day repeated oral administrations of alpelisib as monotherapy (Day 3) and after 22-day repeated oral administrations of alpelisib in combination with repeated doses of amcenestrant (Day 22). PK parameters were determined by non-compartmental analysis.

    Measured: Days 3 and 22 of Cycle 1 (cycle duration=28 days)

  29. Part F: Maximum Plasma Concentration of Alpelisib After Repeated Oral Administrations Alone or in Combination With Amcenestrant

    Blood samples were collected after 3-day repeated oral administrations of alpelisib as monotherapy (Day 3) and after 22-day repeated oral administrations of alpelisib in combination with repeated doses of amcenestrant (Day 22). PK parameters were determined by non-compartmental analysis.

    Measured: Days 3 and 22 of Cycle 1 (cycle duration=28 days)

  30. Part F: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours of Alpelisib After Repeated Oral Administrations Alone or in Combination With Amcenestrant

    Blood samples were collected after 3-day repeated oral administrations of alpelisib as monotherapy (Day 3) and after 22-day repeated oral administrations of alpelisib in combination with repeated doses of amcenestrant (Day 22). PK parameters were determined by non-compartmental analysis.

    Measured: Days 3 and 22 of Cycle 1 (cycle duration=28 days)

  31. Parts H and I: Time to Reach Maximum Plasma Concentration of Everolimus After First Dose and Repeated Oral Administrations in Combination With Amcenestrant

    Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of everolimus in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.

    Measured: Days 1 and 22 of Cycle 1 (cycle duration=28 days)

  32. Parts H and I: Maximum Plasma Concentration of Everolimus After First Dose and Repeated Oral Administrations in Combination With Amcenestrant

    Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of everolimus in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.

    Measured: Days 1 and 22 of Cycle 1 (cycle duration=28 days)

  33. Parts H and I: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours of Everolimus After First Dose and Repeated Oral Administrations in Combination With Amcenestrant

    Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of everolimus in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.

    Measured: Days 1 and 22 of Cycle 1 (cycle duration=28 days)

  34. Part J: Time to Reach Maximum Plasma Concentration of Abemaciclib and Its Metabolites M2, M18 and M20 After First Dose and Repeated Oral Administrations in Combination With Amcenestrant

    Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of abemaciclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.

    Measured: Days 1 and 22 of Cycle 1 (cycle duration=28 days)

  35. Part J: Maximum Plasma Concentration of Abemaciclib and Its Metabolites M2, M18 and M20 After First Dose and Repeated Oral Administrations in Combination With Amcenestrant

    Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of abemaciclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.

    Measured: Days 1 and 22 of Cycle 1 (cycle duration=28 days)

  36. Part J: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Abemaciclib and Its Metabolites M2, M18 and M20 After First Dose and Repeated Oral Administrations in Combination With Amcenestrant

    Blood samples were collected after single dose (Day 1) and repeated oral administrations (Day 22) of abemaciclib in combination with amcenestrant. PK parameters were determined by non-compartmental analysis.

    Measured: Days 1 and 22 of Cycle 1 (cycle duration=28 days)

  37. Parts A, B, J: Post/Pre--Treatment Ratio of 4 Beta (β)-Hydroxycholesterol

    Ratios of 4β-hydroxycholesterol concentrations were calculated from plasma samples collected before and after amcenestrant administration.

    Measured: Pre-treatment on Day 1 of Cycle 1; post-treatment on Day 22 of Cycle 1, Day 1 and Day 28 (only for Part J) of Cycle 2 (cycle duration=28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Sep 2017
  2. Study start20 Sep 2017
  3. Primary completion8 Nov 2024
  4. Study completion8 Nov 2024

Why it stopped: Sponsor decision to prematurely stop the study, not linked to any safety concern.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
136 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03284957
Sponsor's protocol ID
TED14856
Other IDs
U1111-1189-4896, 2024-512997-89, 2017-000690-36, 2017
Acronym
AMEERA-1
Status last verified
Nov 2025
First submitted
13 Sep 2017
Last updated
24 Nov 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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

Publications

  • Bardia A, Chandarlapaty S, Linden HM, Ulaner GA, Gosselin A, Cartot-Cotton S, Cohen P, Doroumian S, Paux G, Celanovic M, Pelekanou V, Ming JE, Ternes N, Bouaboula M, Lee JS, Bauchet AL, Campone M. AMEERA-1 phase 1/2 study of amcenestrant, SAR439859, in postmenopausal women with ER-positive/HER2-negative advanced breast cancer. Nat Commun. 2022 Jul 15;13(1):4116. doi: 10.1038/s41467-022-31668-8.

    PubMed 35840573

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Amcenestrant, Palbociclib and Alpelisib in people with Breast Cancer, run by Sanofi at 25 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in France, United States, Canada, Czechia, Spain and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Parts A, C, F, H, J: Number of Participants With Study Treatment-Related Dose-Limiting Toxicities (DLTs) (time frame: Cycle 1 Day 1 to Cycle 1 Day 28 (cycle duration=28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03284957, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2025.

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