Marengo Therapeutics and Gilead Sciences Collaborate on Clinical Study of Invikafusp alfa and Trodelvy® in Metastatic Breast Cancers

Marengo Therapeutics, Inc., a clinical-stage biotechnology company based in Cambridge, Massachusetts, is pioneering an innovative method to activate T cells that target the Vβ chain of the T cell receptor. This approach is intended to select the optimal T cell subsets to combat cancer. Marengo has announced a new clinical study collaboration and supply agreement with Gilead Sciences, Inc. This collaboration aims to study the combination of Marengo's STAR0602 (Invikafusp alfa), a first-in-class TCR Vβ selective dual T cell agonist, with Gilead's Trodelvy (sacituzumab govitecan-hziy), a Trop-2-directed antibody-drug conjugate (ADC).

The combination therapy will be evaluated in a new multi-center Phase I/II clinical study named START-002. This study will focus on adult patients with metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, and metastatic triple-negative breast cancer (TNBC). Marengo will sponsor the trial, while Gilead will supply Trodelvy.

The planned trial aims to begin shortly and will assess the safety, tolerability, and preliminary efficacy of the combination therapy in patients with metastatic TNBC or metastatic HR+/HER2- breast cancer. The study seeks to explore a novel therapeutic strategy that may provide new treatment options for cancer patients.

Kevin Chin, M.D., Chief Medical Officer of Marengo Therapeutics, expressed optimism about the clinical potential of combining their selective dual T cell activator with Gilead's ADC, Trodelvy. He emphasized that this innovative approach leverages the strengths of both modalities to target and potentially eliminate cancer cells more effectively. The combination has the potential to deliver cytotoxic agents directly to tumors, releasing more tumor antigens for selectively activated and expanded Vβ6/10 T cells to recognize, thereby building long-term immune memory. This could significantly improve outcomes for cancer patients.

Under the collaboration and supply agreement, Gilead will provide Trodelvy, and Marengo will conduct and sponsor the combination study. Both companies will retain all development and commercial rights to their respective compounds, whether used as monotherapies or in combination therapies.

It's important to note that the combination of invikafusp alfa and sacituzumab govitecan-hziy is still investigational and has not been approved by any health authority globally. The safety and efficacy of this combination have not yet been established.

Marengo Therapeutics is a clinical-stage biotech company that develops novel TCR-targeting antibodies. These antibodies selectively modulate common and disease-specific T cell subsets of the germline TCR repertoire, aiming to provide lifelong protection against cancer and other diseases. Marengo's proprietary Selective T Cell Activation Repertoire (STAR) platform leverages a comprehensive understanding of T cell function and receptor signaling to create treatments that enable the immune system to defeat cancer.

The STAR™ Platform is a multi-specific antibody-fusion platform derived from Marengo's proprietary library of antibodies that target germline-encoded variable (V)β regions of the TCR. These are fused to different T cell co-stimulatory moieties, promoting a distinct mechanism of action that encourages durable anti-tumor Vβ T cell responses.

The lead program from Marengo's STAR platform is STAR0602. This T cell activator targets a common Vβ T cell subset present in all cancers. By combining a novel non-clonal mode of TCR activation with a T cell co-stimulator in the same molecule, STAR0602 promotes the expansion of a new population of clonally enriched, effector memory Vβ T cells. This enhances tumor immune responses and promotes the durable clearance of tumors. Preclinical testing of STAR0602 has shown potent anti-tumor activity in both mouse and human ex vivo tumor models.

The ongoing START-001 clinical study is a Phase 1/2 trial evaluating the safety, tolerability, and preliminary clinical activity of STAR0602 as a single agent in biomarker-selected patients with advanced antigen-rich solid tumors, including PD-1 refractory and rare tumors. This open-label, multi-center trial consists of two parts: Phase 1 dose escalation and Phase 2 dose expansion.