• New designation expands on first Fast Track Designation in TMB-H colorectal cancer and is supported by monotherapy responses across multiple tumor types in the STARt-001 study
• Invikafusp alfa believed to be first immuno-oncology T-cell agonist to receive Fast Track Designation in a biomarker-defined, tissue-agnostic indication
• New designation supported by updated Phase 2 data in this population, which will be featured in an oral presentation at the European Society for Medical Oncology (ESMO) Congress 2026 on October 23

Marengo Therapeutics Inc., a clinical-stage biotechnology company pioneering precision immunotherapies for oncology and inflammation and immunology (I&I), announced that the U.S. Food and Drug Administration (FDA) has granted a second Fast Track Designation (FTD) to invikafusp alfa for the treatment of unresectable, locally advanced, or metastatic, tumor mutational burden high (TMB-H) solid tumors that have progressed following prior treatment including immune checkpoint inhibition and who have no satisfactory treatment options.

The new designation expands invikafusp alfa's Fast Track status from a single tumor type, TMB-H colorectal cancer (granted January 2025), to TMB-H solid tumors regardless of their tissue of origin. It is supported by objective responses across multiple tumor types, including colorectal, gastric, breast, urothelial, endometrial, gastroesophageal, head and neck, and lung cancers, in the ongoing Phase 1/2 STARt-001 study, with initial data presented at the Society for Immunotherapy of Cancer (SITC) 2025 Annual Meeting. Updated Phase 2 results will be presented in an oral session at ESMO 2026 in Madrid on October 23.

"Years ago, when we pursued the tumor-agnostic TMB-H approval for pembrolizumab, the premise was that a high mutational burden gives T cells more to recognize. Yet many patients with TMB-H tumors do not respond to PD-1 blockades, such as pembrolizumab, or progress after it and are left with few treatment options," said Eric Rubin, M.D., member of Marengo's Scientific Advisory Board and former Senior Vice President of Global Clinical Oncology at Merck, where he led the initial development of pembrolizumab. "Invikafusp alfa takes a fundamentally different approach: rather than releasing a checkpoint on exhausted T cells, it directly expands new T cells that can act on that antigen-rich landscape. That makes it a compelling candidate for patients whose tumors do not or no longer respond to PD-1-directed therapy, regardless of where the tumor arises."

"A second Fast Track Designation, now in a pan-tumor setting, reinforces our conviction that invikafusp alfa can become a next-generation, tissue-agnostic immuno-oncology backbone," said Ke Liu, M.D., Ph.D., Chief Development Officer of Marengo Therapeutics. "Across multiple clinical data sets, invikafusp alfa has shown encouraging monotherapy activity in heavily pretreated patients across tumor types that were either insensitive to checkpoint inhibitors or progressed after PD-1–directed therapy. In parallel, we are evaluating invikafusp alfa in combination with standard-of-care therapies, including an antibody-drug conjugate, to support its potential in earlier lines of therapy. We look forward to presenting Phase 2 STARt-001 data at ESMO later this month."