evofosfamide + ipilimumab

Evofosfamide + ipilimumab is a combination therapy under investigation for advanced solid malignancies, especially in immunologically "cold" tumors that are resistant to immunotherapy. Evofosfamide is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard (Br-IPM), designed to release its active DNA cross-linking agent in severely hypoxic tumor microenvironments[1][5]. By alleviating tumor hypoxia, evofosfamide may enhance T-cell mediated anti-tumor response and may improve the efficacy of checkpoint inhibitors like ipilimumab[1][3]. Ipilimumab is a monoclonal antibody targeting CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4), which acts as a T-cell checkpoint inhibitor, thereby promoting T-cell activation and proliferation[1]. In a Phase I, dose-escalation trial, this combination showed evidence of activity in heavily pretreated patients with castration-resistant prostate cancer, pancreatic cancer, immunotherapy-resistant melanoma, and HPV-negative head and neck cancer. Most adverse events were grade 1–2, with no new safety signals.

Other names

evofosfamide + ipilimumabTH-302 + ipilimumab