Genentech, Syndax expand HDAC-PD-L1 combination pact

Syndax sees HDAC inhibitors as a way to dial down the immunosuppressive effects of immune regulatory cells. (Image: Genentech)

Genentech and Syndax have expanded their exploration of the effects of combining HDAC and PD-L1 inhibitors. The new agreement clears the Roche subsidiary to test its Tecentriq in combination with Syndax’s entinostat in a subset of breast cancer patients.

Syndax and Genentech began working together in 2015. That deal gave Syndax the chance to run a phase 1b/2 trial of its oral, immune regulatory cell-targeting entinostat and Tecentriq in patients with triple-negative breast cancer. Syndax is yet to complete enrollment in the phase 2 portion of the trial. But the partners already see the combination as promising enough to justify further investment.

This time around, Genentech will assess the effect of the combination in second-line patients with HR+, HER2- metastatic breast cancer. The study will form part of the phase Ib/II adaptive platform set up by Roche to cut the time and resources needed assess the efficacy of drug combinations.

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Success would expand the list of breast cancers in which checkpoint inhibitors have shown promise.

“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,” Syndax CEO Briggs Morrison, M.D. said in a statement.

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Genentech’s interest in adding the HDAC inhibitor to its PD-L1 blocker stems from evidence of the effect of the combination on anti-tumor activity. Syndax and other developers of HDAC inhibitors see the drugs as a way to dial down the immunosuppressive effects of immune regulatory cells. Doing so could enable checkpoint inhibitors such as Tecentriq to spark more devastating attacks on tumors. 

Belief in that mechanism has led Syndax to initiate clinical trials to test entinostat with Tecentriq and rival PD-1/PD-L1 drugs from Merck and Pfizer. Those combinations are targeting multiple indications, including melanoma and ovarian cancer.