PharmaShots Interview: Sanofi’s Chris Soria Shares Insights on Amcenestrant for the Treatment of Breast Cancer
In an interview with PharmaShots, Chris Soria, Global Project Head of Amcenestrant at Sanofi shared his views on the updated data of Amcenestrant in the P-I/II (AMEERA-1) study for ER+/HER2−metastatic breast cancer, presented at SABCS 2021
Shots:
- The P-I/II (AMEERA-1) study evaluated amcenestrant as monothx. & in combination with targeted therapies in postmenopausal women with ER+/HER2- MBC
- In a pooled analysis of 35 patients in the P-I (AMEERA-1) trial, amcenestrant + palbociclib showed encouraging antitumor activity, ORR (34%) & CBR (74%). The combination has a favorable overall safety profile with TRAEs similar to amcenestrant monothx. with no cardiac or ocular side effects
- Amcenestrant is being studied in multiple ongoing clinical trials to evaluate the potential of oral endocrine backbone therapy across multiple treatment lines. The P-III (AMEERA-6) trial has been initiated in the collaboration with the BIG, AFT & EORTC
Tuba: Can we start by discussing the trial design of the AMEERA-1 study? (Including patient segments)
Chris Soria: AMEERA-1 is an open-label, Phase 1/2, first-in-human study designed to evaluate Sanofi’s oral selective estrogen receptor degrader (SERD), amcenestrant, as a monotherapy and in combination with targeted therapies in postmenopausal women with ER+/HER2- MBC. The study is ongoing and continues to enroll patients.
Parts A (dose escalation) and B (dose expansion) were designed to determine the maximum tolerated dose of amcenestrant administered as monotherapy. Parts C and D are evaluating dose-escalation and expansion for amcenestrant in combination with palbociclib; Parts F and G are evaluating amcenestrant in combination with alpelisib; Parts H and I are evaluating amcenestrant in combination with everolimus; Parts J and K are evaluating amcenestrant in combination with abemaciclib; each pair is used to determine the recommended Phase 2 dose for the combination and to characterize its safety profile. Primary efficacy objectives include antitumor activity by objective response rate (ORR) and clinical benefit rate (CBR) per RECIST v1.1 criteria, as well as characterizing the overall safety profile of amcenestrant as a monotherapy and in combination with specific targeted agents.
Eligible patients include women with locally advanced or metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) disease and at least six months of prior exposure to endocrine therapy, including patients with early relapse while on adjuvant endocrine therapy that was initiated more than 24 months ago, or who relapsed less than 12 months after completion of adjuvant endocrine therapy.
Tuba: Can we recap the results presented at ASCO in brief for our readers?
Chris Soria: At ASCO 2021, we shared Phase 1 data from the AMEERA-1 trial. In a pooled analysis of 35 patients, amcenestrant in combination with palbociclib showed encouraging antitumor activity, with an objective response rate (ORR) of 34% and a clinical benefit rate (CBR) of 74%. Amcenestrant in combination with palbociclib also demonstrated a favorable overall safety profile with treatment-related adverse events (TRAEs) similar to those observed with amcenestrant monotherapy and no significant cardiac or ocular side effects.
While the AMEERA-1 study and several others evaluating amcenestrant are ongoing, we believe it is not able to see this kind of activity in patients with ER+ MBC where there is a clear need for new therapeutic options. These data support its potential to become a new endocrine backbone therapy for ER+/HER2- breast cancer as part of our broad ongoing development program.
Tuba: Now coming back to the latest results presented during ESMO, the subgroup analysis?
Chris Soria: At ESMO 2021, we shared a subgroup analysis of the AMEERA-1 initial combination data presented at ASCO 2021. This analysis shows encouraging objective response and clinical benefit rates in combination with palbociclib regardless of ESR1 mutation status.
Tuba: There are multiple additional studies being conducted for amcenestrant in breast cancer. What are the differences among these studies? Are they for a different line of therapy (can you kindly share the details)?
Chris Soria: Sanofi is evaluating amcenestrant in multiple ongoing clinical trials. This comprehensive clinical program – also known as AMEERA – has been designed to evaluate its potential as a best-in-class oral endocrine backbone therapy across several treatment lines, including: as a single agent in second-line or later lines of treatment of ER+/HER2- MBC (AMEERA-3), in combination with palbociclib in the first-line treatment of ER+/HER2- MBC (AMEERA-5), and to explore its potential in early-stage breast cancer patients in the adjuvant setting (AMEERA-6). The pivotal Phase 2 AMEERA-3 and Phase 3 AMEERA-5 clinical trials are now fully enrolled. The Phase 3 AMEERA-6 trial, in partnership with the Breast International Group (BIG), Alliance Foundation Trials (AFT), and the European Organization for Research and Treatment of Cancer (EORTC) has been initiated.
Tuba: Can we talk about Breast cancer (various patient segments such HER2+ve/-ve or BRCA+ve/-ve other biomarkers and subgroups) epidemiology and other details?
Chris Soria: MBC is the spread of the disease from the breast to another part of the body. Today existing treatments are intended to delay disease progression or worsening of cancer with an aim to prolong survival, however, there is no cure. Approximately three out of four breast cancers are estrogen receptor-positive (ER+), meaning that the cancer cells have receptors that use a person’s own estrogen to grow.
Standard treatment for ER+ MBC includes anti-estrogen therapies or endocrine therapies. Most endocrine therapies inhibit tumor growth by either lowering estrogen levels or blocking the estrogen from activating the estrogen receptors. In ER+ breast cancer, cancer cells commonly develop resistance to endocrine therapy over time and long-term treatment may become a challenge. When this resistance occurs, patients may go through several different treatments in succession and it can have a serious impact on the quality of life for people living with MBC.
A different approach involves binding to estrogen receptors in breast cancer cells, inhibiting their normal function and triggering their degradation so they can no longer be used by tumor cells to grow – this is a class known as selective estrogen receptor degrader (SERD). The challenge our researchers took on was to design a molecule that, if taken in pill form, could potentially be stable enough to reach the tumor's insufficient dose before being metabolized, bind to estrogen receptors, and degrade them. Amcenestrant is currently under clinical investigation and its safety and efficacy have not been evaluated by any regulatory authority.
Tuba: When is Sanofi planning to file amcenestrant for approval with the USA and EU? Any timelines in mind?
Chris Soria: We anticipate top-line results from the AMEERA-3 study in Q1 2022, which will inform potential discussions with regulatory authorities.
Tuba: Breast cancer is a very crowded space with lots of competitors. How do you think amcenestrant will make its mark and be different from others?
Chris Soria: ER+ breast cancer, especially metastatic breast cancer, is very difficult to treat because many develop resistance to therapy and current treatments can cause patients to have a poor quality of life with serious, long-term side effects. We believe amcenestrant has the potential to be a new endocrine backbone therapy across treatment settings.
Source: Pexels
About Author:
Chris Soria is the Global Project Head, amcenestrant at Sanofi. Chris brings a broad set of cross-functional leadership experiences to his role having served in roles of increasing responsibility within both US and Global Oncology organizations including 16 years here at Sanofi/Genzyme and 8 years at Roche. Chris is a graduate of Purdue University with a Doctor of Pharmacy (PharmD) degree.
