Invikafusp Alfa Shows Promise in Treating Antigen-Rich GI Tumors

On July 2, 2025, at the ESMO Gastrointestinal Cancers Congress held in Barcelona, Spain, researchers presented key findings regarding invikafusp alfa, a groundbreaking therapeutic agent that has demonstrated significant antitumor activity in patients with advanced gastrointestinal (GI) tumors, including those that are resistant or naive to PD-(L)1 inhibitors. This dual T-cell agonist, also known as STAR0602, was shown to produce a 23.5% overall response rate (ORR) in tumors characterized by high tumor mutational burden (TMB-H) during the phase 1/2 STARt-001 trial (NCT05592626).

The study included 17 patients with TMB-H GI tumors, revealing a 63% disease control rate. Notably, among the 12 patients with metastatic colorectal cancer (mCRC), the ORR was 25%, while the ORR for patients with microsatellite instability-high (MSI-H) tumors reached 33.3%. These results underscore the potential of invikafusp alfa as a monotherapy option in an area of oncology that has traditionally faced challenges, particularly in patients who have exhausted existing treatment avenues.

Dr. Elena Elez, MD, PhD, the lead author of the study and an attending physician at the Gastrointestinal Tumors Service of the Medical Oncology Service at Vall d'Hebron University Hospital in Barcelona, emphasized the favorable safety profile of invikafusp alfa. The most common treatment-related adverse effects (TRAEs) were transient and low-grade, with no occurrences of grade 4 TRAEs or treatment-related deaths reported. Cytokine release syndrome (CRS) was noted in 87.0% of patients but was manageable, predominantly presenting as grade 1 or 2.

The STARt-001 trial is particularly noteworthy because it does not employ primary prophylaxis with corticosteroids or tocilizumab, and it avoided step-up dosing, which could complicate treatment protocols. Elez stated, "The U.S. FDA has previously granted fast track designation for invikafusp alfa in TMB-H mCRC. Phase 2 dose-expansion cohorts are ongoing to confirm the efficacy signal from phase 1."

Invikafusp alfa operates by selectively activating and expanding memory-like effector T cells, particularly targeting Vβ6 and Vβ10 cell populations. This innovative approach aims to restore antitumor T-cell responses in vivo, an essential mechanism when considering treatment for advanced solid tumors.

The safety and efficacy findings from this trial are expected to pave the way for future research and clinical applications. As further cohorts are evaluated, the oncology community anticipates clearer insights into the potential of invikafusp alfa as a viable treatment option for patients with advanced, antigen-rich GI tumors. The trial results highlight an important shift in the landscape of cancer therapeutics, where treatment options for resistant tumor types are critically needed.

As the field of immunotherapy continues to evolve, the implications of invikafusp alfa’s success may lead to broader applications in oncology, particularly for patients facing limited therapeutic options due to resistance to standard treatments. Continued monitoring of the ongoing trials will be crucial for understanding the long-term benefits and safety of this innovative treatment approach.