KEY TAKEAWAYS
- Amcenestrant is being tested in postmenopausal women with ER+/HER2- advanced breast cancer in AMEERA-1.
- The study assessed the amcenestrant’s anticancer efficacy and recommended an antitumor activity.
- Patients received amcenestrant 20-600 mg QD in the dosage escalation phase, and 400 mg QD was chosen as RP2D.
- ER inhibition, degradation, and decreased ESR1 mutations, including Y537S.
- Amcenestrant at RP2D 400 mg QD for monotherapy is well-tolerated with no dose-limiting toxicities and shows preliminary anticancer.
Amcenestrant (NCT03284957) is a selective estrogen receptor (ER) degrader evaluated in the Phase 1/2 open-label, single-arm AMEERA-1 study in postmenopausal women with ER+/HER2- advanced breast cancer. These women have typically been highly pretreated (including targeted therapies and fulvestrant). Patients in Part A (n = 16) were given amcenestrant 20-600 mg QD during the dose-escalation phase. 400 mg QD was chosen as the recommended Phase 2 dose (RP2D) for the dose expansion phase (Part B: n = 49) because of the lack of dose-limiting toxicities, paired functional 18F-fluoroestradiol positron emission tomography, and pharmacokinetics.
There were no treatment-related cardiac or ocular toxicities of clinical significance and no adverse events of grade ≥ 3. Both the interim analysis (3/55) and the final analysis (10.9%) for the primary endpoint, objective response rate (ORR), in Part B were low. Thirteen out of forty-six patients (28.3%) experienced therapeutic benefits. Baseline ESR1 wild-type and mutant patients had overall clinical benefit rate (CBR) rates of 34.6% and 21.1%, respectively (9/26 and 4/19, respectively). Analyses of cell-free DNA and paired tumor biopsies showed a decline in Y537S and other identifiable mutations in ESR1. Amcenestrant, at a recommended phase 2 dose (RP2D) of 400 mg twice daily (QD) for monotherapy, is generally well-tolerated, without dose-limiting toxicities, and shows some evidence of anticancer efficacy regardless of baseline ESR1 mutation status.
Source: https://pubmed.ncbi.nlm.nih.gov/35840573/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03284957
Bardia A, Chandarlapaty S, Linden HM, Ulaner GA, Gosselin A, Cartot-Cotton S, Cohen P, Doroumian S, Paux G, Celanovic M, Pelekanou V, Ming JE, Ternès N, Bouaboula M, Lee JS, Bauchet AL, Campone M. AMEERA-1 phase 1/2 study of amcenestrant, SAR439859, in postmenopausal women with ER-positive/HER2-negative advanced breast cancer. Nat Commun. 2022 Jul 15;13(1):4116. doi: 10.1038/s41467-022-31668-8. PMID: 35840573; PMCID: PMC9284491.
