Trial Outcomes & Findings for 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 (NCT NCT03284957)

Last Updated: 2025-11-24

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

136 participants

Primary outcome timeframe

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

Results posted on

2025-11-24

Participant Flow

This study was conducted at 25 sites in 10 countries between 20-Sep-2017 and 08-Nov-2024. A total of 136 participants were enrolled in the study. Sponsor decided to prematurely stop the study, it was not linked to any safety concern.

The study consisted of dose-escalation phases (Parts A, C, H, J), safety run-in phase (Part F) and dose-expansion phases (Parts B, D, G, I, K). Participants received amcenestrant as monotherapy (Parts A, B) or in combination with palbociclib (Parts C, D), alpelisib (Part F), everolimus (Parts H, I) or abemaciclib (Part J). Parts G and K were never initiated due to the early termination of the study. Reason for not completed = reason for permanent full treatment discontinuation.

Participant milestones

Participant milestones
Measure	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then twice daily (BID) from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part D: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 20 mg Participants received amcenestrant 20 milligrams (mg) capsule orally once daily (QD) in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 150 mg Participants received amcenestrant 150 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Overall Study STARTED	3	3	6	49	9	6	30	8	3	3	3	4	3	1	3	2
Overall Study COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	3	3	6	49	9	6	30	8	3	3	3	4	3	1	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then twice daily (BID) from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part D: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 20 mg Participants received amcenestrant 20 milligrams (mg) capsule orally once daily (QD) in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 150 mg Participants received amcenestrant 150 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Overall Study Adverse Event	0	0	1	1	1	0	4	1	1	0	0	0	0	0	0	0
Overall Study Progressive Disease	3	3	5	45	8	5	18	7	2	3	3	4	3	1	1	2
Overall Study Withdrawal by Subject	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0
Overall Study Other	0	0	0	3	0	1	6	0	0	0	0	0	0	0	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Amcenestrant 20 mg n=3 Participants Participants received amcenestrant 20 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 150 mg n=3 Participants Participants received amcenestrant 150 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=6 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=49 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=9 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=6 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part D: Amcenestrant 200 mg + Palbociclib 125 mg n=30 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=8 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 10 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Total n=136 Participants Total of all reporting groups
Age, Customized 85 years and over	0 Participants n=45 Participants	0 Participants n=12929 Participants	0 Participants n=6349 Participants	0 Participants n=4548 Participants	0 Participants n=28448 Participants	1 Participants n=10 Participants	3 Participants n=1353 Participants	0 Participants n=9 Participants	0 Participants n=6 Participants	2 Participants n=45 Participants	0 Participants n=1675 Participants	0 Participants n=100 Participants	0 Participants n=101 Participants	0 Participants n=101 Participants	0 Participants n=1053 Participants	0 Participants n=152 Participants	6 Participants n=144 Participants
Sex: Female, Male Female	3 Participants n=45 Participants	3 Participants n=12929 Participants	4 Participants n=6349 Participants	3 Participants n=4548 Participants	3 Participants n=28448 Participants	6 Participants n=10 Participants	49 Participants n=1353 Participants	9 Participants n=9 Participants	6 Participants n=6 Participants	30 Participants n=45 Participants	8 Participants n=1675 Participants	3 Participants n=100 Participants	3 Participants n=101 Participants	1 Participants n=101 Participants	3 Participants n=1053 Participants	2 Participants n=152 Participants	136 Participants n=144 Participants
Age, Customized From 18 - 64 years	1 Participants n=45 Participants	3 Participants n=12929 Participants	3 Participants n=6349 Participants	1 Participants n=4548 Participants	3 Participants n=28448 Participants	5 Participants n=10 Participants	29 Participants n=1353 Participants	6 Participants n=9 Participants	2 Participants n=6 Participants	19 Participants n=45 Participants	4 Participants n=1675 Participants	2 Participants n=100 Participants	2 Participants n=101 Participants	1 Participants n=101 Participants	2 Participants n=1053 Participants	0 Participants n=152 Participants	83 Participants n=144 Participants
Age, Customized From 65 - 84 years	2 Participants n=45 Participants	0 Participants n=12929 Participants	1 Participants n=6349 Participants	2 Participants n=4548 Participants	0 Participants n=28448 Participants	0 Participants n=10 Participants	17 Participants n=1353 Participants	3 Participants n=9 Participants	4 Participants n=6 Participants	9 Participants n=45 Participants	4 Participants n=1675 Participants	1 Participants n=100 Participants	1 Participants n=101 Participants	0 Participants n=101 Participants	1 Participants n=1053 Participants	2 Participants n=152 Participants	47 Participants n=144 Participants
Sex: Female, Male Male	0 Participants n=45 Participants	0 Participants n=12929 Participants	0 Participants n=6349 Participants	0 Participants n=4548 Participants	0 Participants n=28448 Participants	0 Participants n=10 Participants	0 Participants n=1353 Participants	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=45 Participants	0 Participants n=1675 Participants	0 Participants n=100 Participants	0 Participants n=101 Participants	0 Participants n=101 Participants	0 Participants n=1053 Participants	0 Participants n=152 Participants	0 Participants n=144 Participants
Race/Ethnicity, Customized White	1 Participants n=45 Participants	3 Participants n=12929 Participants	1 Participants n=6349 Participants	3 Participants n=4548 Participants	2 Participants n=28448 Participants	3 Participants n=10 Participants	35 Participants n=1353 Participants	4 Participants n=9 Participants	4 Participants n=6 Participants	29 Participants n=45 Participants	6 Participants n=1675 Participants	0 Participants n=100 Participants	3 Participants n=101 Participants	0 Participants n=101 Participants	2 Participants n=1053 Participants	2 Participants n=152 Participants	98 Participants n=144 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=45 Participants	0 Participants n=12929 Participants	0 Participants n=6349 Participants	0 Participants n=4548 Participants	0 Participants n=28448 Participants	1 Participants n=10 Participants	0 Participants n=1353 Participants	1 Participants n=9 Participants	0 Participants n=6 Participants	1 Participants n=45 Participants	0 Participants n=1675 Participants	0 Participants n=100 Participants	0 Participants n=101 Participants	0 Participants n=101 Participants	0 Participants n=1053 Participants	0 Participants n=152 Participants	3 Participants n=144 Participants
Race/Ethnicity, Customized Asian	0 Participants n=45 Participants	0 Participants n=12929 Participants	0 Participants n=6349 Participants	0 Participants n=4548 Participants	0 Participants n=28448 Participants	0 Participants n=10 Participants	1 Participants n=1353 Participants	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=45 Participants	0 Participants n=1675 Participants	0 Participants n=100 Participants	0 Participants n=101 Participants	0 Participants n=101 Participants	0 Participants n=1053 Participants	0 Participants n=152 Participants	1 Participants n=144 Participants
Race/Ethnicity, Customized Not reported	2 Participants n=45 Participants	0 Participants n=12929 Participants	2 Participants n=6349 Participants	0 Participants n=4548 Participants	1 Participants n=28448 Participants	2 Participants n=10 Participants	13 Participants n=1353 Participants	3 Participants n=9 Participants	2 Participants n=6 Participants	0 Participants n=45 Participants	2 Participants n=1675 Participants	3 Participants n=100 Participants	0 Participants n=101 Participants	1 Participants n=101 Participants	1 Participants n=1053 Participants	0 Participants n=152 Participants	32 Participants n=144 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=45 Participants	0 Participants n=12929 Participants	1 Participants n=6349 Participants	0 Participants n=4548 Participants	0 Participants n=28448 Participants	0 Participants n=10 Participants	0 Participants n=1353 Participants	1 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=45 Participants	0 Participants n=1675 Participants	0 Participants n=100 Participants	0 Participants n=101 Participants	0 Participants n=101 Participants	0 Participants n=1053 Participants	0 Participants n=152 Participants	2 Participants n=144 Participants

PRIMARY outcome

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

Population: The DLT-evaluable population included participants who received 1 cycle (28 days, oral administration), with intake of at least 75% of intended doses, unless they discontinued study treatment before Cycle 1 completion due to a DLT, and in Part A had an evaluable 18F-fluorestradiol (18F-FES) positron emission tomography (PET) scan at baseline and between Days 11 and 15 of first cycle. Any participant who developed a DLT in Part A despite absence of evaluable 18F-FES-PET scan was also included.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=2 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=2 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=9 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=6 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, C, F, H, J: Number of Participants With Study Treatment-Related Dose-Limiting Toxicities (DLTs)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—

PRIMARY outcome

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

Population: The efficacy population included all treated participants with measurable disease at study entry who provided a baseline and at least 1 post-baseline evaluable tumor assessment. Participants with an early progression as per RECIST v1.1 or who died from disease progression were also included in this set.

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=46 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Part B: Objective Response Rate (ORR) as Determined by Independent Central Review (ICR)	—	—	—	—	—	—	—	—	—	—	10.9 percentage of participants Interval 4.4 to 21.5	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: The safety population included all registered participants exposed to the study treatment, regardless of the amount of treatment administered.

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=30 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts D, I: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs) TEAEs	—	—	—	—	—	—	—	—	—	—	30 Participants	1 Participants	—	—	—	—
Parts D, I: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs) TESAEs	—	—	—	—	—	—	—	—	—	—	8 Participants	1 Participants	—	—	—	—

SECONDARY outcome

Timeframe: 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

Population: The safety population included all registered participants exposed to the study treatment, regardless of the amount of treatment administered.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=6 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=49 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=9 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=8 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, F, H, J: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events TEAEs	3 Participants	3 Participants	6 Participants	49 Participants	9 Participants	3 Participants	6 Participants	8 Participants	3 Participants	3 Participants	3 Participants	3 Participants	4 Participants	2 Participants	—	—
Parts A, B, C, F, H, J: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events TESAEs	0 Participants	1 Participants	3 Participants	15 Participants	2 Participants	1 Participants	1 Participants	6 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=4 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=46 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=9 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=7 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=29 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D, F, H, I, J: Objective Response Rate as Determined by Investigators/Local Radiologists	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	8.7 percentage of participants Interval 3.0 to 18.8	22.2 percentage of participants Interval 4.1 to 55.0	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	0 percentage of participants Interval 0.0 to 39.3	34.5 percentage of participants Interval 20.0 to 51.4	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	0 percentage of participants NA indicates that upper and lower limit of 90% confidence interval (CI) were not estimable due to insufficient number of participants with events.	33.3 percentage of participants Interval 1.7 to 86.5	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	50 percentage of participants NA indicates that the upper and lower limit of 90% CI were not estimable, as there were insufficient numbers of participants with several participants censored prior to any event.

SECONDARY outcome

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=4 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=46 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=9 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=7 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=29 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D, F, H, I, J: Clinical Benefit Rate (CBR) as Determined by Investigators/Local Radiologists	66.7 percentage of participants Interval 13.5 to 98.3	33.3 percentage of participants Interval 1.7 to 86.5	25.0 percentage of participants Interval 1.3 to 75.1	26.1 percentage of participants Interval 15.8 to 38.8	44.4 percentage of participants Interval 16.9 to 74.9	14.3 percentage of participants NA indicates that the upper and lower limit of 90% CI were not estimable, as there were insufficient numbers of participants with several participants censored prior to any event.	50.0 percentage of participants Interval 15.3 to 84.7	75.9 percentage of participants Interval 59.4 to 88.1	50 percentage of participants NA indicates that the upper and lower limit of 90% CI were not estimable, as there were insufficient numbers of participants with several participants censored prior to any event.	33.3 percentage of participants NA indicates that the upper and lower limit of 90% CI were not estimable, as there were insufficient numbers of participants with several participants censored prior to any event.	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	66.7 percentage of participants Interval 13.5 to 98.3	75.0 percentage of participants Interval 24.9 to 98.7	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	66.7 percentage of participants NA indicates that the upper and lower limit of 90% CI were not estimable, as there were insufficient numbers of participants with several participants censored prior to any event.	50 percentage of participants NA indicates that the upper and lower limit of 90% CI were not estimable, as there were insufficient numbers of participants with several participants censored prior to any event.

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=46 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Part B: Clinical Benefit Rate as Determined by Independent Central Review	—	—	—	—	—	—	—	—	—	—	28.3 percentage of participants Interval 17.6 to 41.1	—	—	—	—	—

SECONDARY outcome

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=2 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=10 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D, F, H, I, J: Duration of Response (DOR) as Determined by Investigators/Local Radiologists	—	—	—	NA weeks Interval 32.14 to NA indicates that median and upper limit of 95% CI were not estimable due to insufficient number of participants with events.	32.2 weeks Interval 24.14 to NA indicates that upper limit of 95% CI was not estimable due to insufficient number of participants with events.	—	—	52.4 weeks Interval 16.0 to NA indicates that upper limit of 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	23.9 weeks NA indicates that upper and lower limit of 95% CI could not be calculated for only 1 participant.	—	—	—	11.43 weeks NA indicates that upper and lower limit of 95% CI could not be calculated for only 1 participant.

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=5 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Part B: Duration of Response as Determined by Independent Central Review	—	—	—	—	—	—	—	—	—	—	NA weeks Interval 18.71 to NA indicates that median and upper limit of 95% CI were not estimable due to insufficient number of participants with events.	—	—	—	—	—

SECONDARY outcome

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=4 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=46 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=9 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=7 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=29 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D, F, H, I, J: Progression-Free Survival (PFS) as Determined by Investigators/Local Radiologists	32.3 weeks Interval 8.43 to 90.57	7.9 weeks Interval 7.57 to 39.0	7.7 weeks Interval 7.14 to 32.0	8.3 weeks Interval 7.86 to 23.14	44.3 weeks Interval 7.43 to 80.43	NA weeks NA indicates that median, upper and lower limit of 95% CI were not estimable due to insufficient number of participants with events.	60.0 weeks Interval 7.43 to NA indicates that upper limit of 95% CI was not estimable due to insufficient number of participants with events.	79.7 weeks Interval 40.0 to NA indicates that upper limit of 95% CI was not estimable due to insufficient number of participants with events.	NA weeks NA indicates that median, upper and lower limit of 95% CI were not estimable due to insufficient number of participants with events.	NA weeks NA indicates that median, upper and lower limit of 95% CI were not estimable due to insufficient number of participants with events.	7.3 weeks Interval 6.29 to 15.29	31.3 weeks Interval 5.29 to 41.71	31.3 weeks Interval 6.14 to 31.57	NA weeks NA indicates that median, upper and lower limit of 95% CI were not estimable due to insufficient number of participants with events.	NA weeks NA indicates that median, upper and lower limit of 95% CI were not estimable due to insufficient number of participants with events.	NA weeks NA indicates that median, upper and lower limit of 95% CI were not estimable due to insufficient number of participants with events.

SECONDARY outcome

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

Population: Analysis was performed on the efficacy population. As pre-specified in statistical analysis plan (SAP), analysis was performed on pooled population \[Part A and B: Amcenestrant (Dose \>20 mg); Parts C and D: Amcenestrant 200 mg + Palbociclib 125 mg\] based on the pharmacodynamic effect to maximize sample size within each arm to provide more robust estimates. Only participants with data collected for each specified category are reported.

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=59 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=38 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D: Objective Response Rate as Determined by Investigators/Local Radiologists According to Estrogen Receptor 1 (ESR1) Mutation at Baseline Wild-Type	—	—	—	—	—	—	—	—	—	—	13.3 percentage of participants Interval 4.7 to 28.0	33.3 percentage of participants Interval 18.6 to 50.9	—	—	—	—
Parts A, B, C, D: Objective Response Rate as Determined by Investigators/Local Radiologists According to Estrogen Receptor 1 (ESR1) Mutation at Baseline Mutated	—	—	—	—	—	—	—	—	—	—	3.6 percentage of participants Interval 0.2 to 15.9	27.3 percentage of participants Interval 7.9 to 56.4	—	—	—	—
Parts A, B, C, D: Objective Response Rate as Determined by Investigators/Local Radiologists According to Estrogen Receptor 1 (ESR1) Mutation at Baseline Unknown	—	—	—	—	—	—	—	—	—	—	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	—	—	—	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=46 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Part B: Objective Response Rate as Determined by Independent Central Review According to Estrogen Receptor 1 Mutation at Baseline Wild-Type	—	—	—	—	—	—	—	—	—	—	15.4 percentage of participants Interval 5.4 to 31.8	—	—	—	—	—
Part B: Objective Response Rate as Determined by Independent Central Review According to Estrogen Receptor 1 Mutation at Baseline Mutated	—	—	—	—	—	—	—	—	—	—	5.3 percentage of participants Interval 0.3 to 22.6	—	—	—	—	—
Part B: Objective Response Rate as Determined by Independent Central Review According to Estrogen Receptor 1 Mutation at Baseline Unknown	—	—	—	—	—	—	—	—	—	—	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	—	—	—	—	—

SECONDARY outcome

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

Population: Analysis was performed on the efficacy population. As pre-specified in SAP, analysis was performed on pooled population \[Part A and B: Amcenestrant (Dose \>20 mg); Parts C and D: Amcenestrant 200 mg + Palbociclib 125 mg\] based on the pharmacodynamic effect to maximize sample size within each arm to provide more robust estimates. Only participants with data collected for each specified category are reported.

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=59 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=38 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D: Clinical Benefit Rate as Determined by Investigators/Local Radiologists According to Estrogen Receptor 1 Mutation at Baseline Wild-Type	—	—	—	—	—	—	—	—	—	—	36.7 percentage of participants Interval 22.1 to 53.3	70.4 percentage of participants Interval 52.9 to 84.3	—	—	—	—
Parts A, B, C, D: Clinical Benefit Rate as Determined by Investigators/Local Radiologists According to Estrogen Receptor 1 Mutation at Baseline Mutated	—	—	—	—	—	—	—	—	—	—	32.1 percentage of participants Interval 17.9 to 49.4	63.6 percentage of participants Interval 35.0 to 86.5	—	—	—	—
Parts A, B, C, D: Clinical Benefit Rate as Determined by Investigators/Local Radiologists According to Estrogen Receptor 1 Mutation at Baseline Unknown	—	—	—	—	—	—	—	—	—	—	0 percentage of participants NA indicates that upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	—	—	—	—	—

SECONDARY outcome

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=4 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=10 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts B, D, I: Time to First Confirmed Response as Determined by Investigators/Local Radiologists	—	—	—	—	—	—	—	—	—	—	8.1 weeks Interval 8.0 to 40.0	16.2 weeks Interval 8.0 to 32.0	—	—	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=5 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Part B: Time to First Confirmed Response as Determined by Independent Central Review	—	—	—	—	—	—	—	—	—	—	31.1 weeks Interval 23.0 to 68.0	—	—	—	—	—

SECONDARY outcome

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

Population: The safety population included all registered participants exposed to the study treatment, regardless of the amount of treatment administered.

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=6 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Part A: Number of Participants With 18F-Fluorestradiol Positron Emission Tomography Percentage Reduction ≥90% Reduction	2 Participants	3 Participants	2 Participants	—	—	—	—	—	—	—	0 Participants	3 Participants	2 Participants	—	—	—
Part A: Number of Participants With 18F-Fluorestradiol Positron Emission Tomography Percentage Reduction ≥70% Reduction	3 Participants	3 Participants	2 Participants	—	—	—	—	—	—	—	1 Participants	3 Participants	3 Participants	—	—	—
Part A: Number of Participants With 18F-Fluorestradiol Positron Emission Tomography Percentage Reduction ≥50% Reduction	3 Participants	3 Participants	2 Participants	—	—	—	—	—	—	—	1 Participants	3 Participants	4 Participants	—	—	—
Part A: Number of Participants With 18F-Fluorestradiol Positron Emission Tomography Percentage Reduction ≥30% Reduction	3 Participants	3 Participants	3 Participants	—	—	—	—	—	—	—	1 Participants	3 Participants	4 Participants	—	—	—

SECONDARY outcome

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

Population: The PK population included all participants from the safety population with at least 1 evaluable treatment concentration after study treatment administration. Only participants with data collected at specified timepoint are reported.

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).

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=6 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=16 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=8 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=19 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D, H, I, J: Time Interval Between Administration and the Sampling Preceding the First Concentration Above the Lower Limit of Quantification (LLOQ) (Tlag) of Amcenestrant After a Single Oral Administration	0.00 hour Interval 0.0 to 0.0	0.00 hour Interval 0.0 to 0.0	0.00 hour Interval 0.0 to 0.0	0.00 hour Interval 0.0 to 1.02	0.00 hour Interval 0.0 to 1.0	0.00 hour Interval 0.0 to 0.98	0.00 hour Interval 0.0 to 1.0	0.470 hour Interval 0.0 to 1.08	0.00 hour Interval 0.0 to 0.98	0.00 hour Interval 0.0 to 0.0	0.00 hour Interval 0.0 to 0.5	0.00 hour Interval 0.0 to 1.58	0.00 hour Interval 0.0 to 0.5	0.00 hour Interval 0.0 to 0.0	0.00 hour Interval 0.0 to 0.0	—

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=6 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=16 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=8 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=19 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D, H, I, J: Time to Reach Maximum Plasma Concentration (Tmax) of Amcenestrant After a Single Oral Administration	3.00 hour Interval 1.5 to 3.83	3.03 hour Interval 2.02 to 4.0	2.98 hour Interval 2.0 to 5.95	3.98 hour Interval 1.97 to 9.98	5.82 hour Interval 2.0 to 9.12	4.02 hour Interval 3.0 to 4.05	4.97 hour Interval 1.0 to 6.13	3.03 hour Interval 2.0 to 23.9	3.98 hour Interval 2.0 to 7.92	4.00 hour Interval 4.0 to 4.0	1.52 hour Interval 1.5 to 2.0	3.00 hour Interval 3.0 to 24.77	2.98 hour Interval 1.98 to 4.02	3.88 hour Interval 3.0 to 4.0	3.50 hour Interval 3.0 to 4.0	—

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=6 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=16 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=8 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=19 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D, H, I, J: Maximum Plasma Concentration (Cmax) of Amcenestrant After a Single Oral Administration	4740 ng/mL Standard Deviation 2920	7010 ng/mL Standard Deviation 4180	4620 ng/mL Standard Deviation 2740	6020 ng/mL Standard Deviation 2810	2270 ng/mL Standard Deviation 1130	1700 ng/mL Standard Deviation 355	5470 ng/mL Standard Deviation 1280	2500 ng/mL Standard Deviation 1110	1940 ng/mL Standard Deviation 664	2330 ng/mL Standard Deviation NA NA indicates that standard deviation (SD) was not estimable for only 1 participant.	187 ng/mL Standard Deviation 46.7	1310 ng/mL Standard Deviation 1380	1650 ng/mL Standard Deviation 1340	4500 ng/mL Standard Deviation 2860	5360 ng/mL Standard Deviation 750	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=6 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=16 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=8 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=17 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
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	40400 ng*h/mL Standard Deviation 17500	61100 ng*h/mL Standard Deviation 36300	28200 ng*h/mL Standard Deviation 16900	50900 ng*h/mL Standard Deviation 26000	21300 ng*h/mL Standard Deviation 5910	14100 ng*h/mL Standard Deviation 3190	46400 ng*h/mL Standard Deviation 4400	21400 ng*h/mL Standard Deviation 10000	20900 ng*h/mL Standard Deviation 4330	17900 ng*h/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.	1040 ng*h/mL Standard Deviation 560	9140 ng*h/mL Standard Deviation 8730	13600 ng*h/mL Standard Deviation 13800	36500 ng*h/mL Standard Deviation 25100	38000 ng*h/mL Standard Deviation 13800	—

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=3 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=13 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=8 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=5 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=13 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D, F, H, I, J: Time to Reach Maximum Plasma Concentration of Amcenestrant After Repeated Oral Administrations	2.95 hour Interval 2.02 to 3.78	3.00 hour Interval 3.0 to 4.0	2.98 hour Interval 2.0 to 3.0	3.00 hour Interval 1.02 to 6.0	4.88 hour Interval 1.37 to 8.17	3.22 hour Interval 1.97 to 3.98	4.00 hour Interval 1.83 to 10.0	4.00 hour Interval 1.75 to 6.0	2.47 hour Interval 2.03 to 4.03	4.17 hour Interval 3.95 to 5.92	2.17 hour Interval 2.0 to 4.02	2.97 hour Interval 2.93 to 3.0	2.07 hour Interval 2.0 to 3.03	4.07 hour Interval 4.07 to 4.07	2.67 hour Interval 2.05 to 3.0	3.33 hour Interval 3.33 to 3.33

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=3 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=13 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=8 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=5 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=13 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D, F, H, I, J: Maximum Plasma Concentration of Amcenestrant After Repeated Oral Administrations	4020 ng/mL Standard Deviation 2460	5570 ng/mL Standard Deviation 962	5200 ng/mL Standard Deviation 296	4380 ng/mL Standard Deviation 1230	2060 ng/mL Standard Deviation 831	4230 ng/mL Standard Deviation 1250	4350 ng/mL Standard Deviation 3190	2120 ng/mL Standard Deviation 691	3300 ng/mL Standard Deviation 1390	2760 ng/mL Standard Deviation 411	218 ng/mL Standard Deviation 95.3	2390 ng/mL Standard Deviation 1200	2150 ng/mL Standard Deviation 873	848 ng/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.	3350 ng/mL Standard Deviation 1230	3820 ng/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=3 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=13 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=8 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=5 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=13 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=2 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
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	36800 ng*h/mL Standard Deviation 23500	42700 ng*h/mL Standard Deviation 11200	36500 ng*h/mL Standard Deviation 7680	43200 ng*h/mL Standard Deviation 16200	20600 ng*h/mL Standard Deviation 7520	30600 ng*h/mL Standard Deviation 11900	33100 ng*h/mL Standard Deviation 11400	17600 ng*h/mL Standard Deviation 7540	28300 ng*h/mL Standard Deviation 21100	25000 ng*h/mL Standard Deviation 7180	1630 ng*h/mL Standard Deviation 1120	15900 ng*h/mL Standard Deviation 7350	13900 ng*h/mL Standard Deviation 4380	8270 ng*h/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.	26600 ng*h/mL Standard Deviation 12900	30300 ng*h/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.

SECONDARY outcome

Timeframe: 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)

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

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=3 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID n=4 Participants Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg n=39 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg n=7 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg n=5 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg n=28 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=2 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID n=3 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts A, B, C, D, F, H, I, J: Plasma Concentration Observed Before Treatment Administration (Ctrough) of Amcenestrant Cycle 1 Day 8	871 ng/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.	302 ng/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.	2220 ng/mL Standard Deviation 1100	665 ng/mL Standard Deviation 581	348 ng/mL Standard Deviation 180	—	389 ng/mL Standard Deviation 234	303 ng/mL Standard Deviation 294	—	—	0 ng/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.	91.4 ng/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.	159 ng/mL Standard Deviation 35.8	—	—	—
Parts A, B, C, D, F, H, I, J: Plasma Concentration Observed Before Treatment Administration (Ctrough) of Amcenestrant Cycle 1 Day 15	—	—	—	553 ng/mL Standard Deviation 605	328 ng/mL Standard Deviation 168	—	243 ng/mL Standard Deviation 151	226 ng/mL Standard Deviation 198	—	—	—	—	—	—	—	—
Parts A, B, C, D, F, H, I, J: Plasma Concentration Observed Before Treatment Administration (Ctrough) of Amcenestrant Cycle 1 Day 21	—	—	—	—	359 ng/mL Standard Deviation 132	—	297 ng/mL Standard Deviation 144	223 ng/mL Standard Deviation 187	—	—	—	—	—	—	—	—
Parts A, B, C, D, F, H, I, J: Plasma Concentration Observed Before Treatment Administration (Ctrough) of Amcenestrant Cycle 1 Day 22	388 ng/mL Standard Deviation 327	348 ng/mL Standard Deviation 197	1510 ng/mL Standard Deviation 1030	598 ng/mL Standard Deviation 460	—	410 ng/mL Standard Deviation 449	—	—	326 ng/mL Standard Deviation 216	346 ng/mL Standard Deviation 128	6.80 ng/mL Standard Deviation 9.62	75.1 ng/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.	76.1 ng/mL Standard Deviation 56.0	114 ng/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.	214 ng/mL Standard Deviation 138	229 ng/mL Standard Deviation NA NA indicates that SD was not estimable for only 1 participant.

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=9 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Part B: Cumulated Amount of Amcenestrant Excreted in Urine From Time 0 to 24 Hours (Ae0-24)	—	—	—	—	—	—	—	—	—	—	30800 ng Standard Deviation 36100	—	—	—	—	—

SECONDARY outcome

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

Population: The food-effect population included participants who received study treatment in fed condition on Cycle 1 Day 3 and in fasted condition on Cycle 1 Day 1 in Part A. As pre-specified in SAP, food effect was assessed in Part A QD regimen cohorts only.

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=1 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=2 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Part A (QD Regimen): Geometric Mean Ratio of Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24) of Amcenestrant	1.12 ratio Interval 0.51 to 2.45	1.38 ratio Interval 0.88 to 2.17	—	—	—	—	—	—	—	—	1.05 ratio Interval 0.6 to 1.83	0.69 ratio Interval 0.31 to 1.5	1.77 ratio Interval 1.2 to 2.62	—	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg n=1 Participants Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg n=3 Participants Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=2 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=1 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=4 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Part A (QD Regimen): Geometric Mean Ratio of Maximum Plasma Concentration of Amcenestrant	1.38 ratio Interval 0.53 to 3.59	1.43 ratio Interval 0.83 to 2.48	—	—	—	—	—	—	—	—	0.80 ratio Interval 0.41 to 1.58	0.41 ratio Interval 0.16 to 1.07	1.67 ratio Interval 1.04 to 2.69	—	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=8 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=19 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts C and D: Time to Reach Maximum Plasma Concentration of Palbociclib After First Dose and Repeated Oral Administrations in Combination With Amcenestrant Cycle 1 Day 1	—	—	—	—	—	—	—	—	—	—	5.70 hour Interval 3.0 to 10.0	3.99 hour Interval 2.02 to 7.98	6.00 hour Interval 2.07 to 24.0	—	—	—
Parts C and D: Time to Reach Maximum Plasma Concentration of Palbociclib After First Dose and Repeated Oral Administrations in Combination With Amcenestrant Cycle 1 Day 21	—	—	—	—	—	—	—	—	—	—	4.10 hour Interval 1.93 to 9.97	6.00 hour Interval 3.02 to 8.08	4.75 hour Interval 3.0 to 9.58	—	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=8 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=19 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Parts C and D: Maximum Plasma Concentration of Palbociclib After First Dose and Repeated Oral Administrations in Combination With Amcenestrant Cycle 1 Day 1	—	—	—	—	—	—	—	—	—	—	70.4 ng/mL Standard Deviation 26.1	64.7 ng/mL Standard Deviation 28.4	62.3 ng/mL Standard Deviation 17.5	—	—	—
Parts C and D: Maximum Plasma Concentration of Palbociclib After First Dose and Repeated Oral Administrations in Combination With Amcenestrant Cycle 1 Day 21	—	—	—	—	—	—	—	—	—	—	98.1 ng/mL Standard Deviation 37.6	59.4 ng/mL Standard Deviation 28.1	96.3 ng/mL Standard Deviation 34.9	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=8 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg n=6 Participants Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg n=19 Participants Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
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 Cycle 1 Day 1	—	—	—	—	—	—	—	—	—	—	1040 ng*h/mL Standard Deviation 257	889 ng*h/mL Standard Deviation 376	949 ng*h/mL Standard Deviation 265	—	—	—
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 Cycle 1 Day 21	—	—	—	—	—	—	—	—	—	—	1660 ng*h/mL Standard Deviation 751	823 ng*h/mL Standard Deviation 266	1570 ng*h/mL Standard Deviation 523	—	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=7 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Part F: Time to Reach Maximum Plasma Concentration of Alpelisib After Repeated Oral Administrations Alone or in Combination With Amcenestrant Cycle 1 Day 3	—	—	—	—	—	—	—	—	—	—	3.02 hour Interval 1.02 to 9.0	—	—	—	—	—
Part F: Time to Reach Maximum Plasma Concentration of Alpelisib After Repeated Oral Administrations Alone or in Combination With Amcenestrant Cycle 1 Day 22	—	—	—	—	—	—	—	—	—	—	1.69 hour Interval 1.25 to 2.12	—	—	—	—	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Part A: Amcenestrant 400 mg Participants received amcenestrant 400 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 600 mg Participants received amcenestrant 600 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 300 mg BID Participants received amcenestrant 300 mg capsule orally once on Cycle 1 Day 1 and then BID from Cycle 1 Day 3 onwards (no dose on Cycle 1 Day 2) in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 200 mg + Palbociclib 125 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part C: Amcenestrant 400 mg + Palbociclib 125 mg Participants received amcenestrant 400 mg capsule orally QD in a fed state along with palbociclib 125 mg capsule orally QD in a fed state for 21 consecutive days followed by 7 days off treatment in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part F: Amcenestrant 200 mg + Alpelisib 300 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state from Cycle 1 Day 4 onwards along with alpelisib 300 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part H: Amcenestrant 200 mg + Everolimus 5 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 5 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part B: Amcenestrant 400 mg n=7 Participants Participants received amcenestrant 400 mg capsule orally QD in a fed or fasted state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part I: Amcenestrant 200 mg + Everolimus 10 mg Participants received amcenestrant 200 mg capsule orally QD in a fed state along with everolimus 10 mg tablet orally QD in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part A: Amcenestrant 200 mg Participants received amcenestrant 200 mg capsule orally QD in a fasted state (no dose on Cycle 1 Day 2, dose administered in a fed state on Cycle 1 Day 3 only) in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 100 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 100 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.	Part J: Amcenestrant 200 mg + Abemaciclib 150 mg BID Participants received amcenestrant 200 mg capsule orally QD in a fed state along with abemaciclib 150 mg tablet orally BID in a fed state in 28-day cycles until disease progression, unacceptable toxicity, participant's wish to stop the study, or any other reason, whichever came first.
Part F: Maximum Plasma Concentration of Alpelisib After Repeated Oral Administrations Alone or in Combination With Amcenestrant Cycle 1 Day 3	—	—	—	—	—	—	—	—	—	—	2430 ng/mL Standard Deviation 631	—	—	—	—	—
Part F: Maximum Plasma Concentration of Alpelisib After Repeated Oral Administrations Alone or in Combination With Amcenestrant Cycle 1 Day 22	—	—	—	—	—	—	—	—	—	—	3480 ng/mL Standard Deviation 516	—	—	—	—	—

SECONDARY outcome

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