A Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab

Tumor hypoxia can lead to poor effector T-cell penetration and immunosuppressive signaling via myeloid-derived suppressor cells, myofibroblasts, and regulatory T-cells. Disruption of these hypoxic regions within the tumor microenvironment by the hypoxia-directed cytotoxic agent evofosfamide may enhance the ability of immune checkpoint inhibitors to reject otherwise resistant solid tumors. The hypothesis tested in this study is that evofosfamide, by specifically targeting the hypoxic tumor microenvironment, may enhance the anti-tumor effects of the immune checkpoint inhibitors zalifrelimab (anti-CTLA-4) and balstilimab (anti-PD-1) in select tumors that are generally resistant to therapy. In the Phase 1 dose escalation part of the study, the maximum tolerated dose (or maximum allowable dose) of evofosfamide in combination with zalifrelimab and balstilimab will be determined. A recommended Phase 2 dose (RP2D) will be determined based on safety and the totality of data. The Phase 2 dose expansion part of the study will evaluate the Phase 2 dose of the triplet combination in 3 cohorts: 1) patients with locally advanced or metastatic castration-resistant prostate cancer; 2) patients with locally advanced or metastatic pancreatic cancer; and 3) patients with locally advanced or metastatic HPV-negative SCCHN. Each cohort expansion will be carried out independently.