A Phase 2 Biomarker-Enriched Study Of Evofosfamide (Th-302) In Patients With Advanced Melanoma.

TPS9089 Background: In melanoma, tumor hypoxia is associated with invasion, angiogenesis, and metastasis formation, as well as treatment resistance such as immune evasion. Evofosfamide (EVO, TH-302) is a hypoxia-activated prodrug designed to release the bis-alkylating DNA crosslinker bromo-isophosphoramide mustard (Br-IPM) when reduced in severe hypoxia. In the Phase 1 study (NCT00495144) of EVO monotherapy, 7 of 36 (19%) patients with advanced melanoma had partial responses and 12 of 36 (33%) stable disease. Dose limiting adverse events included skin and mucosal toxicities. A Phase 2 biomarker-enriched trial was initiated to further evaluate the efficacy of EVO in melanoma, and identify hypoxia and other biomarkers predictive of response. Methods: This Phase 2 trial is a single-arm, multi-center, study investigating the efficacy and safety of EVO monotherapy (NCT01864538). The primary endpoint is 3-mo PFS. The study incorporates a Simon two-stage design (alpha = 0.15; beta = 0.15) based on 3-mo PFS with ...