Marengo’s invikafusp alfa shows promising monotherapy activity in PD-1 resistant gastrointestinal cancers
Invikafusp alfa is a first-in-class dual T cell agonist bispecific antibody that selectively activates Vβ6 and Vβ10 T cell subsets, promoting anti-tumor immunity in PD-1 resistant gastrointestinal cancers.
The phase 1/2 STARt-001 clinical trial presented at ESMO Gastrointestinal Cancers Congress 2025 showed invikafusp alfa elicited a 23% overall response rate (ORR) and a 63% disease control rate (DCR) in heavily pretreated PD-1 resistant TMB-high GI cancer patients.
Patients with metastatic colorectal cancer (CRC), including microsatellite stable (MSS) and MSI-high (MSI-H) subtypes, showed meaningful responses:
ORR was 25% in TMB-H metastatic CRC and 33.3% ORR in MSI-H tumors.
Responses included significant tumor shrinkage in patients with MSS colorectal cancer resistant to multiple prior therapies and PD-1 resistant gastroesophageal junction cancer.
Invikafusp alfa demonstrated tumor regression in 53% of treated patients and showed manageable safety consistent with its selective T cell activation mechanism.
Based on these results, the US FDA granted fast track designation for invikafusp alfa as a treatment for TMB-H advanced colorectal cancer.
Experts highlight invikafusp alfa's potential as a new backbone immunotherapy for PD-1 refractory gastrointestinal tumors where checkpoint inhibitors have limited efficacy.
Plans are underway to expand patient selection and trial scope to optimize identification of those who will benefit most from this therapy.