Syndax, Genentech to Test Combo Therapy for HR-positive, HER2-negative Metastatic Breast Cancer

Syndax, Genentech to Test Combo Therapy for HR-positive, HER2-negative Metastatic Breast Cancer

An upcoming Phase 1b/2 trial will evaluate Syndax Pharmaceuticals‘ investigational therapy entinostat in combination with Genentech‘s Tecentriq (atezolizumab) in women with hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have received one previous line of therapy.

The trial is part of a new clinical collaboration between the two companies. It will be conducted by Genentech, and will be inserted into Roche’s MORPHEUS cancer development platform ­that aims to develop immunotherapy combination treatments more rapidly and efficiently. Genentech is a member of the Roche group.

Entinostat is an oral small molecule that inhibits the function of class I histone deacetylases (HDAC) — it prevents HDACs from adding acetyl molecules to certain proteins, a modification that determines protein activity and function.

This allows entinostat to block immunosuppressive cells — like myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs) — enhancing the immune system’s ability to recognize and kill tumor cells.

Tecentriq is a monoclonal antibody that binds PD-L1, a protein that helps cancers evade the immune system’s response. When the PD-L1 protein, produced by cancer cells, binds its receptor PD-1, a kind of “off switch” is triggered in immune cells, impairing them from seeing cancer cells as malignant.

Drugs targeting either one of these proteins — PD-1 or PD-L1 — block this interaction, boosting the immune response against cancer cells.

“This collaboration represents further validation of the ongoing interest to test the potential ability of Syndax’s entinostat to enhance the effectiveness of an immuno-oncology therapy in an area of unmet medical need,” Briggs W. Morrison, MD, chief executive officer of Syndax, said in a press release.

This is the second partnership between Syndax and Genentech. They are also testing the combination of entinostat and Tecentriq in patients with advanced triple-negative breast cancer. The ENCORE 602 Phase 1b/2 trial (NCT02708680), currently recruiting participants, includes an open-label dose determination phase (Phase 1b) followed by an expansion phase (Phase 2).

“While checkpoint inhibitors have shown initial promise in triple-negative breast cancer, there is a clear need to augment the effectiveness of such therapies in the setting of HR+, HER2- breast cancer,” Morrison added.

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