Marengo Therapeutics Unveils Promising Invikafusp Alfa Data at ESMO 2025

Marengo Therapeutics, a clinical-stage biotechnology company based in Cambridge, Massachusetts, has presented promising new clinical data regarding its first-in-class selective dual T cell agonist, Invikafusp alfa, during a late-breaking oral session at the European Society of Medical Oncology (ESMO) Gastrointestinal Cancers Congress 2025. The presentation, delivered by Dr. Elena Elez from the Vall d'Hebron Institute of Oncology, highlighted the monotherapy's efficacy in patients with PD-1 resistant gastrointestinal tumors, which include various subtypes of metastatic colorectal cancer (mCRC) and gastroesophageal junction (GEJ) tumors.

According to the data shared on July 2, 2025, Invikafusp alfa demonstrated a disease control rate (DCR) of 63%, a tumor regression rate of 53%, and an objective response rate (ORR) of 23% in heavily pretreated patients with high tumor mutational burden (TMB-H) gastrointestinal cancers. These results are particularly significant as they suggest a potential new treatment option for patients whose tumors have shown resistance to existing PD-1 inhibitors.

The STARt-001 Phase 1/2 trial, evaluating the safety and preliminary efficacy of Invikafusp alfa, has garnered attention for its innovative approach to targeting T cell subsets, specifically the Vβ6 and Vβ10 T cells. This dual T cell agonist is designed to enhance immune responses against tumors by promoting durable anti-tumor immunity, a critical factor for patients with advanced cancer where traditional therapies have failed.

Dr. Zhen Su, the CEO of Marengo Therapeutics, expressed enthusiasm regarding the results, stating, "Invikafusp's ability to drive meaningful responses in both PD-1-resistant tumors and across diverse tissue types underscores the potential of our precision T cell activation platform to deliver real impact as a new class of immuno-oncology backbone in immunotherapy-refractory tumors."

Expert opinions on the significance of these findings further emphasize the potential of Invikafusp alfa. Dr. Aparna Parikh, a GI oncologist at Massachusetts General Hospital and a prominent figure in colorectal cancer research, remarked, "The activity we are observing with Invikafusp in both colorectal and gastroesophageal junction tumors is highly compelling and highlights the clinical potential of a novel T cell agonist approach."

The data presented at ESMO 2025 not only supports the ongoing development of Invikafusp alfa but also contributes to the growing body of evidence regarding the efficacy of T cell agonists in treating difficult-to-manage cancers. The study's findings are particularly relevant in the context of increasing incidences of PD-1 resistance in various cancer types, a challenge that has necessitated the exploration of alternative therapeutic strategies.

Marengo Therapeutics is currently enrolling patients in the Phase 2a expansion cohorts of the STARt-001 trial, focusing on multiple tumor types, including metastatic colorectal cancer and other antigen-rich solid tumors. The positive interim results provide a promising outlook for future clinical applications and underscore the need for continued research and development in this area.

As the landscape of cancer treatment evolves, the introduction of innovative therapies like Invikafusp alfa could represent a significant advancement in the quest for effective treatments for patients with resistant tumors. The implications of this research extend beyond individual patient outcomes, potentially reshaping the future of cancer immunotherapy.

For ongoing updates, interested parties can visit the clinical trial registry at clinicaltrials.gov (Identifier: NCT05592626) or contact Marengo Therapeutics directly for more information on participation in ongoing studies.