Sanofi has discontinued the clinical development program for amcenestrant due to unsatisfactory results from the phase 3AMEERA-5 trial.
The amcenestrant (SAR 439859) global clinical development program will be discontinued, according to a press release by Sanofi, the parent company. Amcenestrant is an investigational oral selective estrogen receptor degrader (SERD).1
The decision to discontinue the program come from the results of the prespecified interim analysis of the AMEERA-5 trial (NCT04478266). This phase 3 trial evaluated amcenestrant in combination with palbociclib (Ibrance) vs letrozole (Femara) combined with palbociclib in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer.
The AMEERA-5 study is a randomized, double-blind study that assessed the safety and efficacy of amcenestrant and palbociclib in the first line. A total of 1068 patients were randomized 1:1 to receive oral amcenestrant and palbociclib or oral letrozole and palbociclib. This study’s primary end point was progression-free survival, and secondary end points include overall survival (OS), objective response rate, duration of response, and clinical benefit rate.2
An independent data monitoring committee recommended stopping the trial after learning that the amcenestrant and palbociclib combination did not meet the prespecified boundary for continuation compared with the control arm. Investigators observed no new safety signals, and the trial patients will be transitioned to letrozole plus palbociclib treatment or to another standard of care therapy, according to their physician.
Sanofi continues to review the data and will share the results in the future. Other studies of amcenestrant, including AMEERA-6 (NCT05128773) which is evaluating it in early-stage breast cancer, will be discontinued.
The AMEERA-6 trial is a randomized, double-blind study that evaluated amcenestrant vs tamoxifen (Soltamox) in patients with hormone receptor-positive early breast cancer who discontinued adjuvant aromatase inhibitor therapy because of toxicity. Investigators randomized patients to receive oral amcenestrant or oral tamoxifen. The primary end point of the study was invasive breast cancer-free survival, and the secondary end points were invasive disease-free survival, OS, distant recurrence-free survival, locoregional recurrence-free survival, and safety.3
“While we are disappointed by this outcome, our research will further the scientific understanding of endocrine therapies in people with breast cancer. Our sincere gratitude goes to the patients, families, and healthcare professionals involved in the amcenestrant clinical development program. Oncology remains a priority area for Sanofi, and we will continue to pursue transformative research to develop new medicines for people living with cancer,” said John Reed, MD, PhD, global head of Research and Development at Sanofi, said.
Sanofi also announced earlier in the year that the phase 2 AMEERA-3 trial (NCT04059484) had not met the primary end point of progression-free survival vs physician’s choice in patients with ER+/HER2- advanced or metastatic breast cancer.
1. Sanofi provides update on amcenestrant clinical development program. Press release. Sanofi; August 17, 2022. Accessed August 17, 2022. https://bit.ly/3ArwdbP
2. Amcenestrant (SAR439859) plus palbociclib as first line therapy for patients with ER (+) HER2(-) advanced breast cancer (AMEERA-5). ClinicalTrials.gov. Updated May 10, 2022. Accessed August 17, 2022. https://clinicaltrials.gov/ct2/show/record/NCT04478266?term=AMEERA-5&draw=2&rank=1
3. Study of amcenestrant (SAR439859) versus tamoxifen for patients with hormone receptor-positive (HR+) early breast cancer, who have discontinued adjuvant aromatase inhibitor therapy due to treatment-related toxicity (AMEERA-6). ClinicalTrials.gov. Updated August 3, 2022. Accessed August 17, 2022. https://clinicaltrials.gov/ct2/show/record/NCT05128773?term=AMEERA-6&draw=2&rank=1