PharmaShots Interview: Sanofi's Laurent Debussche Shares Insight on the Need of SERDs for ER+ Breast Cancer

In an interview with PharmaShots, Laurent Debussche, Global Head of Molecular Oncology Research Therapeutic Area at Sanofi shares insight on the SERDs data being presented at ASCO 2021 and highlight the need for this type of innovation for ER+ breast cancer

Shots:

Sanofi has presented the data from P-I AMEERA-1 study evaluating amcenestrant in combination with palbociclib & demonstrated anti-tumor activity with an ORR of 34% and a clinical benefit rate of 74%
Amcenestrant in combination with Palbociclib also demonstrated a favorable OS profile, with treatment related AEs attributable to amcenestrant like those observed with monothx. and without signs of significant cardiac or ocular side effects
Amcenestrant is an oral SERD that antagonizes and degrades the estrogen receptor (ER) resulting in inhibition of the ER signaling pathway

Tuba: Can we have the key points of the data of SERDs presented at ASCO?

Laurent: In a pooled analysis of Phase 1 data from the AMEERA-1 study presented at the 2021 ASCO Annual Meeting, the investigational oral selective estrogen receptor degrader (SERD) amcenestrant in combination with palbociclib demonstrated encouraging anti-tumor activity, with an objective response rate of 34% and a clinical benefit rate of 74%. Amcenestrant in combination with palbociclib also demonstrated a favorable overall safety profile, with treatment related adverse events attributable to amcenestrant similar to those observed with monotherapy and without signs of significant cardiac or ocular side effects. [GCIH1]

Tuba: What role will these SERDs play in treating breast cancer and advancing the science behind the SERDs?

Laurent: A significant need exists for more treatment options for estrogen receptor-positive (ER+) breast cancer, the most common type of breast cancer, accounting for about 3/4 of all breast cancers diagnosed today. [GCIH2] As metastatic breast cancer patients progress through currently available treatment options, tumors become resistant ' or stop responding ' to treatment, and time spent on each therapy decreases, underscoring the need for new therapies and novel ways to overcome drug resistance. [GCIH3]

Amcenestrant is an oral SERD that antagonizes and degrades the estrogen receptor (ER) resulting in inhibition of the ER signaling pathway. [GCIH4] We're committed to responding to the unique needs of those living with ER+ metastatic breast cancer and investigating amcenestrant as a potential best-in-class oral endocrine backbone therapy across treatment lines through our broad clinical program.

Tuba: What motivates Sanofi to work on the oral dosage of SERDs?

Laurent: Over the years, healthcare providers have expressed frustration over the significant unmet needs in breast cancer. The metastatic breast cancer community has also voiced its collective desire for new treatment options and a better balance between potential effectiveness and impacts on quality of life. [GCIH5]

Recognizing the need for new solutions, Sanofi's scientists took on the challenge to develop a SERD treatment option that aims to balance metabolic stability and receptor binding potency with an oral administration. [GCIH6]

Tuba: Put some light on your latest collaboration for evaluating Amcenestrant in the adjuvant setting.

Laurent: We are collaborating with leading academic cooperative groups, the Breast International Group (BIG), the European Organization for Research and Treatment of Cancer (EORTC), and Alliance Foundation Trials (AFT), on Phase 3 AMEERA-6 study.

The Phase 3 AMEERA-6 study will evaluate the efficacy and safety of Sanofi's amcenestrant versus tamoxifen for women with ER+ breast cancer who were unable to continue their adjuvant aromatase inhibitor (AI) therapy. [GCIH7] It will be a registrational study with invasive disease-free survival as the primary endpoint.

AMEERA-6 is expected to begin recruiting patients in H2 2021. [GCIH8] The current timeline for the full readout of the study findings is 2H 2026. If study recruitment happens earlier and quicker, the results could be available earlier.[GCIH9] We look forward to executing this study with the global expertise of the world-leading academic groups we are collaborating with.

Tuba: What is the MOA of amcenestrant? What is the other researchers involved with the therapy?

Laurent: Amcenestrant is an oral SERD that antagonizes and degrades the ER resulting in inhibition of the ER signaling pathway.

The comprehensive development program for amcenestrant has been designed to evaluate its role: (1) as a single agent in second-line or later lines of treatment of ER+/HER2- metastatic breast cancer, (2) in combination with palbociclib in the first-line treatment of ER+/HER2- metastatic breast cancer, and (3) to explore its potential in early-stage breast cancer patients in the adjuvant setting. Late last year, the Phase 3 AMEERA-5 clinical trial investigating amcenestrant in combination with palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, as a first-line therapy for patients with ER+ metastatic breast cancer, was initiated.

A pivotal study (AMEERA-3) of amcenestrant versus physician's choice in locally advanced or metastatic ER+ breast cancer is fully recruited. The pivotal readout is now expected in H2 2021. Of note, the trial recently passed a Data Safety Monitoring Committee (DSMC) futility analysis.[GCIH10]

Additionally, in June Sanofi announced a partnership with leading groups delivering practice-changing breast cancer research, the Breast International Group (BIG), the European Organization for Research and Treatment of Cancer (EORTC), and the Alliance Foundation Trials (AFT), to initiate a pivotal trial of amcenestrant in the adjuvant setting. The Phase 3 AMEERA-6 study will evaluate the efficacy and safety of Sanofi's amcenestrant vs. tamoxifen for women with ER+ breast cancer who were unable to continue their adjuvant AI therapy.[GCIH11]

Tuba: Do you feel competition in this space? Can you name a few of them for our readers?

Laurent: We're committed to investigating amcenestrant as a potential oral backbone therapy across treatment lines in ER+ metastatic breast cancer and are confident in our clinical development program. We're moving quickly to the earlier lines of therapy and are also working strategically to generate both monotherapy and combination data so that as a potential endocrine backbone therapy, physicians may in the future have data available to use amcenestrant across multiple lines of therapy and in combination with multiple targeted agents. We are planning additional studies that will seek to generate amcenestrant data in combination with other targeted agents, and in other subpopulations of patients, including work with Quantum Leap and the I-SPY program, and with various Investigator Sponsored Studies all with the aim of building important pieces of the amcenestrant story. [GCIH12]

We look forward to continuing research around amcenestrant and exploring its full potential for patients with ER+ metastatic breast cancer.

Tuba: When can we expect the availability of the product for patients with ER+ metastatic breast cancer?

Laurent: The pivotal readout of AMEERA-3 is now expected in H2 2021. [GCIH13] While we cannot comment on regulatory decisions and product availability at this time, we are confident in our clinical development program and look forward to presenting data that add to the growing body of strong clinical evidence for amcenestrant in ER+ metastatic breast cancer.

Image Source: Emaze

Reference:

[GCIH1] Sanofi AMEERA-1 ASCO Press Release https://www.sanofi.com/en/media-room/press-releases/2021/2021-05-19-23-00-00-2232867

[GCIH2] Sanofi AMEERA-1 ASCO Press Release https://www.sanofi.com/en/media-room/press-releases/2021/2021-05-19-23-00-00-2232867

[GCIH3] MBC Media Narrative (MAT-GLB-2004334-v1.0-01/21)

[GCIH4] Sanofi AMEERA-1 ASCO Press Release https://www.sanofi.com/en/media-room/press-releases/2021/2021-05-19-23-00-00-2232867

[GCIH5] https://www.onclive.com/view/advancing-care-in-metastatic-breast-cancer

[GCIH6] MBC Media Narrative (MAT-GLB-2004334-v1.0-01/21)

[GCIH7]Sanofi BIG Collaboration Press Release https://www.sanofi.com/en/media-room/press-releases/2021/2021-06-04-07-00-00-2241809

[GCIH8] [GCIH8] https://www.onclive.com/view/trial-explores-preoperative-window-for-amcenestrant-therapy-in-early-breast-cancer

[GCIH9] Sanofi ASCO IR Event talking points

[GCIH10]Source: Sanofi AMEERA-1 ASCO Press Release https://www.sanofi.com/en/media-room/press-releases/2021/2021-05-19-23-00-00-2232867

[GCIH11] Sanofi BIG Collaboration Press Release https://www.sanofi.com/en/media-room/press-releases/2021/2021-06-04-07-00-00-2241809

[GCIH12] [GCIH12] Sanofi ASCO IR Event talking points

[GCIH13] Sanofi AMEERA-1 ASCO Press Release https://www.sanofi.com/en/media-room/press-releases/2021/2021-05-19-23-00-00-2232867

About Laurent Debussche:

Laurent Debussche is the Global Head of Molecular Oncology Research Therapeutic Area at Sanofi. He manages one of two Sanofi Oncology Research Therapeutic Areas that involve more than 50 projects and several external collaborations. He has more than 30 years of experience in oncology drug discovery with multiple pre-clinical candidate nominations, and first-in-human clinical projects. Debussche has authored more than 60 scientific publications and was featured in The New York Times as a 'stubborn' cancer scientist. He has a Ph.D. in Biochemistry and Molecular Biology from the University Pierre et Marie Curie and AgroParisTech in Paris and has received a prize from the French Academy of Science in 1993 for the elucidation of the Vitamin B12 biosynthetic pathway.