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AACR 2022 | Phase I study of TAK-676 + pembrolizumab following radiotherapy in late-line NSCLC, TNBC and SCCHN

Benjamin Cooper, MD, NYU Langone Health, New York, NY, discusses a Phase I study (NCT04879849) of TAK-676 and pembrolizumab following radiation therapy in patients with advanced non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), or squamous cell carcinoma of the head and neck (SCCHN) that has progressed on immune checkpoint inhibitors (ICIs). Previous studies examining resistance to immunotherapy have implicated the cGAS/stimulator of interferon genes (STING) pathway, a cytosolic DNA-sensing pathway that drives activation of inflammatory cytokines, in the host immune response against tumors. TAK-676 is an intravenous STING agonist. This family of therapeutics are increasingly understood to have other anti-tumor functions such as modulation of the vasculature and support of tertiary lymphoid structure development. It is hoped that STING agonism and immune agitation via radiation and pembrolizumab therapy will help overcome treatment resistance in these populations. The primary aims of the study are to evaluate efficacy, adverse event incidence and maximum tolerated dose of TAK-676. This interview took place at the American Association for Cancer Research Annual Meeting in New Orleans, LA.