Abstract P1-17-11: Updated data from AMEERA-1: Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), combined with palbociclib in postmenopausal women with ER+/HER2- advanced breast cancer
Authors: Chandarlapaty Sarat , Linden Hannah M , Neven Patrick , Petrakova Katarina , Bardia Aditya , Kabos Peter , Braga Sofia , Boni Valentina , Gosselin Alice , Celanovic Marina , Cohen Patrick , Paux Gautier , Pelekanou Vasiliki , Ternès Nils , Lee Joon Sang , Campone Mario 
Published: March 2022

Abstract
Background: In Arm 2 of the ongoing AMEERA-1 trial (NCT03284957), amcenestrant, an optimized oral SERD combined with the CDK4/6 inhibitor (CDK4/6i) palbociclib demonstrated favorable safety and encouraging antitumor activity among patients with endocrine-resistant ER+/HER2− advanced breast cancer in dose escalation (Part C) and dose expansion (Part D) (Chandarlapaty et al., ASCO 2021; abstract 1058). Here we report an update of safety, antitumor activity data, and progression-free survival (PFS), of amcenestrant 200 mg in combination with palbociclib. Analysis of genomic data, including modulation over time and correlation with clinical outcome, will also be presented. Methods: The trial enrolled postmenopausal women with ER+/HER2- locally-advanced or metastatic breast cancer with disease progression while on ≥ 6 months of prior endocrine therapy (ET) in the advanced setting, or who relapsed on adjuvant ET after the first 2 years of treatment or within 12 months of completing adjuvant ET. Prior chemotherapy (≤ 1) was allowed as well as prior CDK4/6i-based therapy (≤ 1, in Part C only). In this pooled analysis (N = 39), patients in Parts C + D received amcenestrant 200 mg once daily + palbociclib 125 mg (21 days on/7 days off), administered in 28-day cycles. Safety in the pooled analysis was reported using methods previously described (Chandarlapaty et al., ASCO 2021; abstract 1058). Data from investigator-assessed, response-evaluable patients in the pooled analysis without prior exposure to targeted therapies (N = 34) were used to evaluate antitumor activity per RECIST v1.1, including the objective response rate (ORR), clinical benefit rate (CBR), and PFS. Results: At a data cutoff of May 30, 2021, in the pooled analysis (N = 39), the median (range) duration of treatment exposure was 44.3 weeks (1-80). Of 39 patients, 24 (61.5%) had initiated at least 10 cycles (40 weeks) of treatment, with 20/39 (51.3%) still receiving ongoing treatment. Among the 34/39 (87.2%) patients in the response-evaluable population, median follow-up was 48.3 weeks with a PFS probability of being event free at 24 weeks of 78.2% (95% CI: 59.6%; 89.0%). Median PFS is not yet mature, with 14/34 (41.2%) patients having had a PFS event (all were progression events and no deaths occurred). The ORR was 11/34 (32.4%; all partial responses). Clinical benefit at 24 weeks was seen in 25/34 (CBR = 73.5%) patients. Median (range) time to first response was 16.3 weeks (8-32). Amcenestrant treatment-related adverse events (TRAEs) and palbociclib TRAEs, respectively, occurred in 27/39 (69.2%) and 35/39 (89.7%) patients for all grade events and in 5/39 (12.8%) and 18/39 (46.2%) patients for Grade ≥ 3 events. Non-hematological amcenestrant and palbociclib TRAEs are reported in Table 1. Neutrophil count decrease based on hematological laboratory abnormalities was observed in the majority of patients (94.9%; with Grade ≥ 3 in 56.4%).
Conclusions: Among postmenopausal women with endocrine-resistant ER+/HER2- advanced breast cancer, amcenestrant 200 mg in combination with the approved dose of palbociclib continues to demonstrate encouraging long-term antitumor activity, sustained clinical benefit, and a favorable safety profile consistent with previous results. Funding: Sanofi.
Table 1.Non-hematological amcenestrant and palbociclib TRAEs occurring in &gt; 10% of patientsPooled Analysis. Amcenestrant 200 mg + Palbociclib. (Parts C + D; N = 39)Amcenestrant Non-hematological TRAEs, n (%)All GradesGrade ≥ 3–Fatigue7 (17.9)0–Nausea7 (17.9)0–Arthralgia4 (10.3)0–Asthenia4 (10.3)0–Hot flush4 (10.3)0Palbociclib Non-hematological TRAEs, n (%)All GradesGrade ≥ 3–Fatigue12 (30.8)0–Nausea10 (25.6)0–Asthenia4 (10.3)0–Dysgeusia4 (10.3)0–Stomatitis4 (10.3)0
Citation Format: Sarat Chandarlapaty, Hannah M Linden, Patrick Neven, Katarina Petrakova, Aditya Bardia, Peter Kabos, Sofia Braga, Valentina Boni, Alice Gosselin, Marina Celanovic, Patrick Cohen, Gautier Paux, Vasiliki Pelekanou, Nils Ternès, Joon Sang Lee, Mario Campone. Updated data from AMEERA-1: Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), combined with palbociclib in postmenopausal women with ER+/HER2- advanced breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-11.