Sanofi’s Oncology Targets Highlighted at Annual ASCO Meeting

Annual Meeting of the American Society of Clinical Oncology

During the upcoming annual meeting American Society of Clinical Oncology (ASCO) in June 2019, Sanofi’s oncology franchise will present a renewed strategy to address difficult-to-treat and difficult-to-eradicate cancers, including certain types of multiple myeloma, skin cancer, breast cancer, and lung cancer.

Four key molecules in clinical development are the pillars of the company’s late-stage and emerging oncology pipeline, including isatuximab, an investigational anti-CD38 monoclonal antibody; cemiplimab (Libtayo® ; Sanofi US and Regeneron Pharmaceuticals), a PD-1 checkpoint inhibitor; SAR439859, an investigational oral selective estrogen receptor degrader (SERD); and SAR408701, an investigational anti-CEACAM5 antibody-drug conjugate.

We have a strategic focus to address unmet patient needs across many therapeutic areas at Sanofi, and currently oncology makes up a sizeable portion of our late-stage pipeline,” explained John C. Reed, M.D. Ph.D. Executive Vice President, Global Head of Research & Development

“Our oncology pipeline is flourishing, offering a progressively expanding diversity of opportunities to help advance the treatment of a variety of cancers. We are excited to showcase this progress at ASCO,” Reed added.

Relapsed/refractory multiple myeloma

We are particularly excited to share the results from our pivotal Phase III ICARIA-MM trial [NCT02990338] of isatuximab in patients with a difficult-to-treat relapse/refractory multiple myeloma. This is the first of multiple Phase III trials with isatuximab, our wholly-owned molecule under investigation for the treatment of multiple myeloma. We look forward to the presentation of data at ASCO and believe that the ICARIA-MM data serve as the basis for the first regulatory filings of isatuximab.” [1]

John C. Reed, M.D. Ph.D. Executive Vice President, Global Head of Research & Development at Sanofi. He holds a B.A. in chemistry from the University of Virginia, Charlottesville and an M.D. and Ph.D. (Immunology) from the University of Pennsylvania School of Medicine.

Isatuximab is an investigational anti-CD38 monoclonal antibody (mAb) for the treatment of patients with relapsed/refractory multiple myeloma. Developed by Sanofi, the investigational agent targets a specific epitope of CD38 capable of triggering multiple, distinct mechanisms of action that are believed to promote programmed tumor cell death (apoptosis) and immunomodulatory activity.

CD38 is highly and uniformly expressed on multiple myeloma cells and is a cell surface receptor target for antibody-based therapeutics in multiple myeloma and other malignancies. The clinical significance of these findings is under investigation.

The drug is currently being evaluated in multiple ongoing Phase III clinical trials in combination with currently available treatments across the multiple myeloma treatment continuum. Research is also ongoing for the treatment of other hematologic malignancies and solid tumors.

  • A phase 3 randomized, open-label, multicenter study comparing isatuximab, pomalidomide, and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) (Dr. Paul Richardson; Sunday, June 2: Oral Abstract Session, 9:45-12:45 AM, ICARIA presentation,10:57-11:09 AM)
  • Treatment patterns in patients with multiple myeloma (MM): A retrospective study using Medicare data (Dr. Parameswaran Hari; Publication Only)

Advanced cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (CSCC) is one of the most commonly diagnosed skin cancers worldwide. Although the majority of patients with CSCC have a good prognosis when the cancer is found early, the cancer can be especially difficult to treat when it progresses to advanced stages.[2][3][4][5][6]

New longer-term data with cemiplimab, being jointly developed by Regeneron and Sanofi under a global collaboration agreement, offers updated efficacy and safety outcomes that add to the growing body of evidence for cemiplimab in patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation.

Cemiplimab is approved in the U.S., Canada and Brazil, and is under review by the European Commission following a positive opinion by the Committee for Medicinal Products for Human Use (CHMP). In the U.S., the drug is approved for the treatment of patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation.

Cemiplimabe is also being investigated in potential registrational trials in non-small cell lung cancer, basal cell carcinoma and cervical cancer, along with additional trials in squamous cell carcinoma of the head and neck, melanoma, colorectal cancer, prostate cancer, multiple myeloma, Hodgkin’s lymphoma and non-Hodgkin’s lymphoma.

These trials are designed to investigate the drug as monotherapy; in combination with conventional treatments like chemotherapy; or in combination with other investigational agents, including vaccines, oncolytic viruses and bispecific antibodies, among others. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

  • Primary analysis of Phase 2 results of cemiplimab, a human monoclonal anti-PD-1, in patients with locally advanced cutaneous squamous cell carcinoma (Dr. Michael Migden; Saturday, June 1: Poster Display, 1:15-4:15 PM and Poster Discussion, 4:30-6:00 PM)
  • Phase 2 study of cemiplimab, a human monoclonal anti-PD-1, in patients with metastatic cutaneous squamous cell carcinoma (mCSCC ; Group 1): 12 month follow-up (Dr. Alexander Guminski; Monday, June 3: Poster Display, 1:15-4:15 PM)
  • Treatment patterns and outcomes among patients with advanced cutnaeous squamous cell carcinoma in a US community oncology setting (Dr. C. Lance Cowey; Publication Only)
  • Patterns of major surgeries among patients diagnosed with cutaneous squamous cell carcinoma (Chieh-I Chen; Publication Only)

Evolving evidence in breast and lung cancers

Breast cancer is the second most common form of cancer. An estimated 70% of breast cancers are estrogen receptor (ER) positive. SAR439859 is an investigational oral selective estrogen receptor degrader (SERD), a small molecule targeted therapy that binds to estrogen receptors in breast cancer cells to trigger their degradation.

  • Dose-escalation study of SAR439859, an oral selective estrogen receptor (ER) degrader (SERD), in postmenopausal women with ER+/HER2- metastatic breast cancer (Dr. Aditya Bardia; Poster Display, Sunday, June 2, 8:00-11:00 AM)
  • Phase 1/2 dose-escalation and expansion study investigating SAR439859 +/- palbociclib in postmenopausal women with estrogen receptor-positive (ER+)/HER2- metastatic breast cancer (Dr. Aditya Bardia; Poster Display, Sunday, June 2, 8:00-11:00 AM)

Antibody-drug Conjugate

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a cell-surface glycoprotein highly expressed in several tumor types, including non-squamous non-small cell lung cancer (NSQ NSCLC).

CEACAM5, a member of the CEA family of proteins that plays a key role in cell migration, cell invasion, and cell adhesion, is overexpressed by a variety of cancer cell types. Approximately 20% of lung cancers have a high expression of CEACAM5.

SAR408701 is an antibody-drug conjugate ((ADC) which consists of anti-CEACAM5 antibody conjugated to a cytotoxic agent, with potential antineoplastic activity. Upon administration of the anti-CEACAM5 antibody-drug conjugate, the antibody moiety targets CEACAM5 on tumor cells. Following antibody/antigen binding and internalization, the immunoconjugate releases the cytotoxic agent, which results in tumor cell death. The agent is currently being investigated in clinical trials.

  • First-in-human Phase 1 study of the antibody-drug conjugate (ADC) SAR408701 in advanced solid tumors: dose-expansion cohort of patients (pts) with non-squamous non-small cell lung cancer (NSQ NSCLC) (Dr. Anas Gazzah; Poster Display, Sunday, June 2, 8:00-11:00 AM)

Additional abstracts

During the upcoming meeting of the American Society of Clinical Oncology, additional abstract supported by Sanofi include:

Abstract title Abstract number
Oral Abstract, Friday, May 31, 2:45-5:45 PM
Updated results from a randomized phase II study of
cabazitaxel (CAB) versus abiraterone (ABI) or enzalutamide (ENZ) in poor prognosis metastatic CRPC
5003
Poster Session, Saturday, June 1, 1:15-4:15 PM
Cell-free DNA as a biomarker for taxane treatment in
advanced prostate cancer
5070
Cabazitaxel with Abiraterone Versus Abiraterone Alone
Randomized Trial for Extensive Disease Following
Docetaxel: the CHAARTED II Trial:  A trial of the
ECOG-ACRIN Cancer Research Group (EA8153)
TPS5094
HSD3B1 and Overall Survival in Men with Low-Volume
Metastatic Disease Treated with Androgen Deprivation
Therapy or Chemohormonal Therapy in the CHAARTED Randomized Trial
5020
CALGB 90203 (Alliance): Radical prostatectomy (RP) with or
without neoadjuvant chemohormonal therapy (CHT) in men with clinically localized, high-risk prostate cancer (CLHRPC).
5079
Oral Abstract, Saturday, June 1, 3:00-6:00 PM
Association of Colon Cancer (CC) Molecular Signatures with
Prognosis and Oxaliplatin Prediction-Benefit in the MOSAIC
Trial (Multicenter International Study of Oxaliplatin/ 5FU-LV in the Adjuvant Treatment of Colon Cancer)
3503
Clinical Science Symposium, Sunday, June 2, 8:00-9:00 AM
Evolutionary action score of TP53 analysis in pathologically
high-risk HPV-negative head and neck cancer from a phase II clinical trial: NRG Oncology RTOG 0234
6010
Poster Session, Monday, June 3, 8:00-11:00 AM
Repeated centralized MDT resectability assessment during
first-line treatment in 1086 Finnish metastatic colorectal
cancer (mCRC) patients nationwide (prospective RAXO study)
3517
Combination of tissues analysis and immune infiltrate in
localized colon cancer using Using artificial intelligence in
PETACC8 study
3574
Relative Contribution of Clinical and Molecular Features to
Outcome Within Low and High Risk T and N Groups in
Patients with Stage III Colon Cancers (Alliance)
3520
Is the predictive and prognostic impact of sporadic and
familial microsatellite instable stage III colon cancer
different? A pooled analysis of the PETACC8 and NCCTG
N0147 (Alliance) trials
3583

Reference:

[1] Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients (ICARIA-MM) – NCT02990338

[2] Stratigos, Alexander et al. Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline. European Journal of Cancer, Vol 51(14);14, 1989-2007

[3] Califano JA, Lydiatt WM, Nehal KS, et al. Cutaneous squamous cell carcinoma of the head and neck. In: Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. Springer; 2017:171-181.

[4] Skin cancer treatment (PDQ®). National Cancer Institute website. Updated February 1, 2018. Accessed February 13, 2018. [Online]

[5] Jennings L, Schmults CD. Management of high-risk cutaneous squamous cell carcinoma. J Clin Aesthet Dermatol. 2010;3(4):39-48.

[6] Brunner M, Veness MJ, Ch’ng S, Elliott M, Clark JR. Distant metastases from cutaneous squamous cell carcinoma—analysis of AJCC stage IV. Head Neck. 2013;35(1):72-75.