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 an 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.