On November 7, 2025 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering precision immunotherapies for oncology and inflammation & immunology (I&I), reported updated interim results from the ongoing Phase 2 expansion of its lead program, Invikafusp alfa (STAR0602).
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The data were presented in a late-breaking clinical oral presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2025 Annual Meeting. This marks Invikafusp alfa’s fifth major oral presentation, underscoring continued external interest and excitement around the rapid progression of Marengo’s lead program.
"The expanded, pan-tumor single-agent activity of Invikafusp alfa in PD-1 resistant TMB-H cancers across seven major solid tumor indications reinforces our vision for developing a next-generation immuno-oncology (IO) backbone therapy," said Zhen Su, M.D., MBA, Chief Executive Officer of Marengo Therapeutics. "Paired tumor biopsy analyses provide compelling evidence that we are selectively activating and reprogramming Vβ6⁺ T cells within the TIL compartment — a critical mechanism that translates into meaningful clinical benefit. These results validate our first-in-class precision dual T cell activation platform and support our bold mission to overcome PD-1 resistance."
As of the July 15, 2025 data cutoff, 57 patients with TMB-H advanced solid tumors were enrolled across 20 histologies and 46 patients were efficacy-evaluable. Key findings are outlined below.
Pan tumor monotherapy activity in PD-1-resistant TMB-H patients:
20% ORR and 80% DCR observed across seven major tumor types — colorectal, gastric, lung, breast, GEJ, head and neck, and bladder cancers
Responses by indication include gastrointestinal (GI) tumors (28% ORR, 78% DCR), colorectal cancer (CRC) (33% ORR, 67% DCR), and non-small cell lung cancer (NSCLC) (20% ORR, 80% DCR)
Target tumor shrinkage, with 59% of patients experiencing target-lesion regression
Anti-tumor activity observed in both immune checkpoint blockade (ICB)-naïve and ICB-experienced patients, across both primary and secondary PD-1-resistant tumors
Activity in both microsatellite stable (MSS) and microsatellite instability (MSI)-H Tumors, including clinical benefit observed across a range of TMB levels, irrespective of MSI status
A safety profile consistent with the selective T cell activation mechanism of action, treatment-related adverse events (AEs) were transient and manageable with supportive care
Mechanistic activity validated in paired biopsies and blood samples, with evidence of:
Selective Vβ6⁺ T cell expansion consistent with peripheral expansion and intratumoral enrichment of Vβ6⁺ T cells observed following treatment
In vivo TIL reprogramming with robust upregulation of TCR signaling, cytotoxicity, and chemokine expression post-treatment, indicating enhanced immune activation within the tumor microenvironment
Downregulation of immune-suppressive factors and upregulation of activation and cytotoxic markers among patients who experienced tumor shrinkage
Invikafusp alfa is a first-in-class bispecific dual T cell agonist designed to selectively activate and expand Vβ6⁺/Vβ10⁺ T-cell subsets — which represent highest prevalent of tumor-infiltrating lymphocytes (TILs) — to restore and amplify anti-tumor immunity in patients who have progressed on or are insensitive to ICB.
Marengo is advancing a post–PD-1, biomarker-enriched development strategy for Invikafusp alfa, continuing the Phase 2 monotherapy expansion in TMB-H and MSI-H/dMMR solid tumors to further characterize depth and durability of response across priority indications.
To reach broader, frontline patient populations beyond the TMB-H setting, the company is also conducting a Phase 2 combination study with Trodelvy (a TROP2-directed antibody-drug conjugate) in triple-negative breast cancer (TNBC) and HR⁺/HER2⁻ breast cancer to evaluate synergy in ADC + IO combination settings. In parallel, Marengo continues to advance regulatory interactions, including recent receipt of U.S. FDA Fast Track designation for Invikafusp alfa in TMB-H metastatic colorectal cancer (mCRC).
(Press release, Marengo Therapeutics, NOV 7, 2025, View Source [SID1234659649])