Cambridge, Massachusetts, USA, October 23, 2026
Marengo Therapeutics has presented Phase 2 clinical results for invikafusp alfa, an investigational immunotherapy designed to activate selected T-cell populations and fight advanced cancers. Data from the company’s STARt-001 clinical study, presented at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain, demonstrated antitumor activity across eight different tumor types in heavily pretreated patients with tumor mutation burden-high (TMB-H) solid tumors. Among 62 evaluable patients, invikafusp alfa achieved an objective response rate of 18% and a disease control rate of 60%, while tumor shrinkage was observed in 56% of patients. The study included breast, colorectal, endometrial, gastroesophageal junction, gastric, head and neck, non-small cell lung and bladder cancers. These findings are significant because the participants had advanced cancers that were often unresponsive to immune checkpoint blockade or had progressed following earlier immunotherapy. The results support further investigation of selective T-cell activation as a potential approach for patients with limited treatment options.
STARt-001 Trial Demonstrates Activity Across Eight Cancer Types
The STARt-001 Phase 1/2 clinical trial evaluates invikafusp alfa as a single-agent treatment for patients with unresectable, locally advanced or metastatic solid tumors that have shown limited response to immune checkpoint blockade. The Phase 2 results included 62 evaluable patients with TMB-H tumors across eight cancer types. Researchers reported an 18% objective response rate (ORR), meaning that this proportion of patients experienced a measurable reduction in tumor burden meeting established response criteria. The disease control rate reached 60%, including patients who achieved an objective response or maintained stable disease. Tumor shrinkage was observed in 56% of evaluable patients. Activity was seen in both patients who had previously received immune checkpoint blockade and those who had not. Among patients previously treated with checkpoint inhibitors, the ORR was 20%, compared with 14% in checkpoint inhibitor-naïve patients. Disease control rates were 68% and 43%, respectively. Responses were also observed among patients whose cancers had demonstrated primary or secondary resistance to previous checkpoint inhibitor treatment. These results provide an early signal of potential activity across multiple tumor types. However, STARt-001 is a signal-seeking study, and the findings require confirmation in larger patient populations with longer follow-up.
Invikafusp Alfa Activates T Cells Beyond the PD-1 Pathway
Invikafusp alfa, also known as STAR0602, is a first-in-class bispecific dual T-cell agonist developed using Marengo Therapeutics’ proprietary STAR platform. The investigational antibody targets a selected subset of T cells expressing particular variable beta (Vβ) regions of the T-cell receptor. It is designed to combine T-cell receptor activation with a costimulatory signal, promoting the expansion and activation of immune cells capable of recognizing and attacking cancer. This mechanism differs from conventional PD-1 checkpoint inhibitors, which work by blocking inhibitory signals that suppress immune activity. By selectively activating Vβ T-cell populations, invikafusp alfa aims to broaden antitumor immune responses, including in patients whose tumors have not responded adequately to checkpoint blockade. Translational analyses from STARt-001 showed rapid expansion of Vβ6-positive T-cell clonotypes following the first infusion. Researchers also observed increased overlap between T-cell clonotypes detected in blood and tumor samples, consistent with activated immune cells moving into tumor tissue. These biological findings support the proposed mechanism of selective T-cell activation, although further research is needed to establish how these changes relate to durable clinical benefit. The investigational therapy has received two U.S. FDA Fast Track designations, including one covering TMB-H solid tumors regardless of tissue of origin. Fast Track designation supports development and review but does not represent marketing approval.
Advertisement
Safety Profile and Future Oncology Development
The safety analysis included 104 patients who received invikafusp alfa. The company reported a manageable tolerability profile consistent with selective T-cell activation. Cytokine release syndrome was mainly Grade 1 or Grade 2, and no immune effector cell-associated neurotoxicity syndrome or Grade 5 treatment-related adverse events were observed in the reported analysis. These findings are encouraging but do not eliminate the possibility of serious adverse reactions as additional patients receive treatment. Marengo is continuing development through biomarker-selected single-agent studies and combination strategies intended to improve treatment activity in specific cancer populations. The company is also investigating combinations of Vβ6-selective T-cell agonists with antibody-drug conjugates in metastatic breast cancer through the STARt-002 program. Additional analyses from STARt-001 are ongoing, with a more complete clinical dataset expected in 2027. Invikafusp alfa remains investigational and is not an approved cancer treatment. Future studies will need to establish the durability of responses, identify patients most likely to benefit and clarify the therapy’s safety profile. Nevertheless, the Phase 2 results provide a promising foundation for further research into immune therapies that activate selected T-cell populations beyond the established PD-1 pathway.
Source: Marengo Therapeutics press release
