Phase 1/2 trial reports early activity of invikafusp alfa in solid tumors

START-001 is an ongoing, multicenter phase 1/2 monotherapy trial of invikafusp alfa, a bispecific antibody designed to activate selected Vβ6/Vβ10 T-cell subsets. Participants had antigen-rich solid tumors, most of which were resistant to immune checkpoint blockade. Phase 1 enrolled 34 participants and completed dose escalation from 0.01 to 0.16 mg/kg; initial phase 2 enrollment included 18 participants. The primary phase 1 outcomes were safety and dose selection, with antitumor activity assessed in phase 2.

Two participants had reversible dose-limiting toxicities, one at 0.08 mg/kg and one at 0.16 mg/kg. Cytokine release syndrome, mainly grade 1 or 2, was the most common treatment-related adverse event. No treatment-related deaths or non-laboratory grade 4 adverse events were reported. At the 0.08 and 0.12 mg/kg optimal biological doses, the combined cohorts had an objective response rate of 14.8% (4/27), including confirmed partial responses in microsatellite-stable colorectal cancer and PD-L1-negative non-small cell lung cancer. No objective responses occurred below 0.08 mg/kg.

The investigators selected 0.08 mg/kg as the recommended phase 2 dose. These early results support further study but do not establish efficacy or a role in clinical practice; the trial is ongoing, and the reported response data come from small cohorts. The article reports sponsor Marengo Therapeutics’ plans to make individual participant data available after study completion and primary analysis.