A new clinical trial is testing whether combining evofosfamide, a hypoxia-activated drug, with immune checkpoint inhibitors zalifrelimab and balstilimab can overcome resistance in advanced cancers. The approach focuses on disrupting the hypoxic environment within tumors, which is known to block immune responses and foster an immunosuppressive climate. By specifically targeting these oxygen-deprived areas, evofosfamide could open the door for T-cells to attack cancer cells that were previously shielded.

The trial is divided into two parts: a Phase 1 dose-escalation study and a Phase 2 expansion. Researchers will first determine the maximum tolerated dose of evofosfamide alongside the two checkpoint inhibitors, then test the combination in three cancer cohorts: prostate cancer, pancreatic cancer, and HPV-negative head and neck cancer. Each group’s results will be analyzed independently to assess the treatment’s safety and effectiveness.

If successful, the therapy could provide new hope for patients with tumors that have been resistant to other treatments. By combining the ability to disrupt hypoxia with the power of immune checkpoint inhibition, the study may pave the way for a more effective approach to battling difficult-to-treat cancers.

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