Phase 2 Dose Expansion Trial of OBI-3424, a DNA-Alkylating Prodrug, in Patients with Advanced Solid Tumors Expressing AKR1C3

BACKGROUND: OBI-3424 is an investigational small molecule prodrug. In a dose-escalation trial, the OBI-3424 recommended phase 2 dose (RP2D) was 12 mg/m2 administered every 21 days. In this phase 2 dose-expansion trial, we evaluated the safety and efficacy of OBI-3424 in pancreatic adenocarcinoma and other solid tumor types ("basket" cohort). METHODS: Patients with advanced solid tumors and AKR1C3 IHC H-score of ≥ 100 were treated at the RP2D of OBI-3424. Tumor response, progression-free survival (PFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) were assessed (www.clinicaltrials.gov NCT03592264). RESULTS: Of the 29 patients treated, 26 were evaluable for response (pancreatic adenocarcinoma, n = 10; basket cohort, n = 16). In the pancreatic adenocarcinoma cohort, stable disease (SD) was observed in 40.0% of patients and the median PFS and OS durations were 1.35 months and 3.8 months, respectively. In the basket cohort, the objective response rate was 6.3% (1 of 16 patients had a partial response), 50% of patients had SD and the median PFS and OS durations were 2.53 months and 5.32 months, respectively. The most common TEAEs in both cohorts were anemia, fatigue, and thrombocytopenia. CONCLUSION: While OBI-3424 demonstrated a favorable safety profile, limited efficacy led to early trial termination.