Marengo Therapeutics and Gilead Sciences have entered into a clinical study collaboration to evaluate the combination of Marengo’s STAR0602 (Invikafusp alfa) with Gilead’s Trodelvy (sacituzumab govitecan-hziy) for the treatment of metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer and metastatic triple-negative breast cancer (TNBC). The collaboration aims to explore a novel therapeutic strategy that could offer new treatment options for patients with these aggressive forms of breast cancer.
The planned multi-center Phase I/II clinical trial, named START-002, will be sponsored by Marengo Therapeutics. The study will assess the safety, tolerability, and preliminary efficacy of STAR0602 in combination with Trodelvy in patients with metastatic TNBC or metastatic HR+/HER2- breast cancer.
Investigational Combination
The combination of invikafusp alfa and sacituzumab govitecan-hziy is investigational and has not been approved by any health authority globally. The safety and efficacy of this combination have not been established. Invikafusp alfa has recently demonstrated single-agent clinical activity across different PD-1 resistant cancers in the ongoing START-001 Phase 1/2 clinical study.
Mechanism of Action
STAR0602 is a first-in-class TCR Vβ selective dual T cell agonist. It selectively targets a common Vβ T cell subset present in all cancers and, by combining a novel non-clonal mode of TCR activation with a T cell co-stimulator in the same molecule, promotes expansion of a new population of clonally enriched, effector memory Vβ T cells that turbo-charge tumor immune responses and promote durable clearance of tumors. Trodelvy is a Trop-2-directed antibody-drug conjugate (ADC) designed to deliver a cytotoxic payload directly to tumor cells expressing the Trop-2 protein.
Executive Commentary
"We are excited about the clinical potential of combining our novel selective dual T cell activator with Gilead's antibody-drug conjugate, Trodelvy," said Kevin Chin, M.D., Chief Medical Officer of Marengo Therapeutics. "This innovative approach leverages the strengths of two unique modalities to target and potentially eradicate cancer cells more effectively. With the possibility to deliver target cytotoxic agents directly to tumors, which release more tumor antigens for selectively activated and expanded Vβ6/10 T cells to recognize and build long-term immune memory, we believe this combination may have the potential to improve cancer patient outcomes."
Trial Sponsorship and Rights
Under the clinical study collaboration and supply agreement, Gilead will provide Trodelvy to Marengo, who will conduct and sponsor the combination study. Marengo and Gilead will retain all development and commercial rights to their respective compounds, including as monotherapy or as combination therapies.
