Abstract 264P
Background
Amcenestrant is an optimized, oral SERD that has shown favorable safety and encouraging antitumor activity in combination with palbociclib (palbo) in ER+/HER2– aBC. Here, we report updated data, including antitumor activity by subgroups.
Methods
This open-label, phase 1/2 study assessed palbo 125 mg (21 days on, 7 off) + amcenestrant in dose escalation (Part C; n = 15; 200 and 400 mg QD in 28-day cycles) and dose expansion (Part D; n = 30; 200 mg recommended phase 2 dose) in ER+/HER2– aBC patients (pts) with ≥ 6 months of prior endocrine therapy. Antitumor activity was assessed by objective response (OR) rate (ORR; confirmed complete response [CR] and partial response [PR]) and clinical benefit (CB) rate (CBR; CR, PR, or stable disease [SD] ≥ 24 weeks) per RECIST v1.1 in response-evaluable pts without prior CDK4/6 or mTOR inhibitors (n = 35; Part C, n = 6; Part D, n = 29). Subgroup analyses by prior treatment and baseline ESR1 mutation status (wild-type [wt] or mutated [m]) were conducted. ESR1 mutations and genomic profiling were assessed in cfDNA by ddPCR and NGS, respectively.
Results
Subgroup analyses are shown in the table (March, 2021 cut off). CB was observed for 7/8 pts with Y537S, D538G, E380Q, or Y537N baseline ESR1 mutations; OR was observed for 3/8 pts with D538G or E380Q. In 33 response-evaluable pts with baseline NGS data: 23 pts had wtESR1 + other genomic aberrations, with OR in 6/23 (26.1%) and CB in 16/23 (69.6%); of 11/33 pts with OR, 8 pts had wtESR1 (including 1 pt with prior fulvestrant, PIK3CA and PTEN) and 2 pts had no aberration; of 5/33 pts with mESR1 and concurrent aberrations, 2/5 had OR and 4/5 had CB; of 9/33 pts with no CB, genomic aberrations included PIK3CA and TP53. Table: 264P
| Last prior therapy | Baseline ESR1 status by ddPCR | ||||
| Response-evaluable pts (n=35) | Overall | Neo(adjuvant) | Advanced | wtESR1 | mESR1 |
| Best Overall Response, n (%) | |||||
| •Number | 35 | 15 | 20 | 27 | 8 |
| •Complete Response (CR) | 0 | 0 | 0 | 0 | 0 |
| •Partial Response (PR) | 12 (34.3%) | 4 (26.7%) | 8 (40.0%) | 9 (33.3%) | 3 (37.5%) |
| •Stable Disease (SD) | 22 (62.9%) | 10 (66.7%) | 12 (60.0%) | 17 (63.0%) | 5 (62.5%) |
| •Progressive Disease (PD) | 1 (2.9%) | 1 (6.7%) | 0 | 1 (3.7%) | 0 |
| Objective Response Rate, n (%) | 12 (34.3%) | 4 (26.7%) | 8 (40.0%) | 9 (33.3%) | 3 (37.5%) |
| Clinical Benefit Rate, n (%) | 26 (74.3%) | 8 (53.3%) | 18 (90.0%) | 19 (70.4%) | 7 (87.5%) |
Conclusions
Amcenestrant combined with palbociclib showed encouraging OR and CB in pts with ER+/HER2- aBC, irrespective of ESR1 mutation status.
Clinical trial identification
NCT03284957.
Editorial acknowledgement
Editorial support was provided by Rohan Keshwara, PhD, and Julian Martins, MBBS, MA, of inScience Communications (Philadelphia, PA, USA), funded by Sanofi.
Legal entity responsible for the study
Sanofi.
Funding
Sanofi.
Disclosure
S. Chandarlapaty: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Paige.ai; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Paige.ai. H.M. Linden: Other, Personal, Stocks/Shares, An Immediate Family Member: Evolent; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Tolmar; Financial Interests, Institutional, Research Grant: Zionexa; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Zenatalis; Financial Interests, Institutional, Research Grant: Zymeworks. P. Neven: Financial Interests, Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Roche; Financial Interests, Institutional, Advisory Role: Radius Health; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: Lilly; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: Roche. K. Petrakova: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Radius Health; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Daiichi Pharma/AstraZeneca; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Biothernostics Inc.; Financial Interests, Personal, Advisory Board: Phillips; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Foundation Medicine; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Radius Health; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Daiichi Pharma/AstraZeneca. P. Kabos: Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Sanofi; Financial Interests, Personal, Research Grant: Radius Health. V. Boni: Financial Interests, Personal, Other, Honoraria: Loxo; Financial Interests, Personal, Other, Honoraria: IDEAYA Biosciences; Financial Interests, Personal, Advisory Role: OncoArt; Financial Interests, Personal, Advisory Role: Guidepoint Global; Financial Interests, Personal, Speaker’s Bureau: Solti; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Loxo; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: CytomX Therapeutics; Financial Interests, Institutional, Research Grant: Kura Oncology; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Menarini; Financial Interests, Institutional, Research Grant: Synthon; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Merus; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Zenith Epigenetics; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Adaptimmune; Financial Interests, Institutional, Research Grant: Alkermes; Financial Interests, Institutional, Research Grant: Array BioPharma; Financial Interests, Institutional, Research Grant: BioNTech AG; Financial Interests, Institutional, Research Grant: Boston Biomedical; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim Pharmaceuticals Inc; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Bayer HealthCare Pharmaceuticals, Inc.; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: START. V. Pelekanou, N. Ternès, A. Gosselin, M. Celanovic, P. Cohen, G. Paux: Financial Interests, Personal, Full or part-time Employment: Sanofi. M. Campone: Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Sanofi; Financial Interests, Personal and Institutional, Research Grant: Pierre Fabre; Financial Interests, Personal and Institutional, Research Grant: Takeda; Financial Interests, Personal and Institutional, Research Grant: AbbVie; Financial Interests, Personal and Institutional, Research Grant: Servier; Financial Interests, Personal and Institutional, Research Grant: Sandoz; Financial Interests, Personal and Institutional, Research Grant: Accord; Financial Interests, Personal and Institutional, Speaker’s Bureau: Novartis; Financial Interests, Personal and Institutional, Speaker’s Bureau: Lilly. All other authors have declared no conflicts of interest.