Phase 1/2 Trial Will Investigate STAR0602 Plus Nivolumab in Metastatic Prostate Cancer

A newly registered phase 1b/2 clinical trial will investigate invikafusp alfa (STAR0602) combined with nivolumab in patients with metastatic castration-resistant prostate cancer (mCRPC). The study introduces a distinctive immunotherapy strategy aimed at activating selected T-cell populations and potentially overcoming resistance to immune checkpoint blockade.

STAR0602 is an experimental bifunctional antibody–cytokine fusion protein that selectively recognizes T-cell receptors containing Vβ6 or Vβ10 variable regions while delivering an interleukin-2 (IL-2) signal. In simpler terms, it is an experimental drug that targets specific groups of T cells and delivers a signal that activates them and helps them multiply, potentially strengthening the immune system’s ability to fight cancer. This dual mechanism stimulates and expands specific populations of CD4+ and CD8+ T cells, including cells exhibiting memory-like characteristics. Unlike conventional tumor antigen-directed T-cell engagers, STAR0602 does not require recognition of a specific prostate cancer antigen. Combining it with nivolumab, a PD-1 inhibitor, could potentially enhance antitumor immune activity while limiting inhibitory signaling.

The rationale is supported by preclinical findings demonstrating tumor regression in multiple experimental models, including some resistant to PD-1 inhibition. More recently, a phase 1/2 study published in Nature Medicine, reported early clinical activity with STAR0602 monotherapy in patients with advanced solid tumors. At selected biologically active doses, 4 of 27 patients achieved objective responses (14.8%), including responses in tumors traditionally considered poorly responsive to checkpoint inhibitors. Treatment also produced measurable expansion of the targeted T-cell populations.

The earlier study identified cytokine release syndrome as the most common treatment-related adverse event, predominantly grade 1 or 2. Two reversible dose-limiting toxicities occurred during dose escalation, with no treatment-related deaths reported in the published analysis. These findings supported continued clinical development, although the reported response rate was obtained across different tumor types and cannot be interpreted as prostate-specific efficacy.

Clinical trial.