Phase 1b of WNT inhibitor ipafricept (IPA, decoy receptor for WNT ligands) with carboplatin (C) and paclitaxel (P) in recurrent platinum-sensitive ovarian cancer (OC).

Abstract

2515Background: The WNT pathway is an important oncologic driver of OC. The first-in-class recombinant fusion protein IPA blocks WNT signaling through binding of WNT ligands. In patient-derived OC xenografts, IPA inhibits growth, reduces cancer stem cell frequency, promotes differentiation, synergizes with taxanes and shows greatest efficacy when given 2 to 3 days before the taxane. In Phase 1a, IPA was well tolerated with dysgeusia, fatigue, muscle spasms and anorexia as most common adverse events (AEs). Target modulation was observed in hair follicles at ≥ 2.5 mg/kg every 3 weeks (q3w). Consequent to the clinical experience with, mainly, vantictumab (VAN), a 2nd WNT inhibitor, serum biochemical markers of bone turnover were used to trigger bone-protective zoledronic acid (ZA)therapy, if appropriate. Methods: Dose escalation started with a standard 3+3 design for IPA/C/P with q3w intravenous IPA on Day 1, in cycles 1 to 6 with C (AUC = 5 mg/mL · min) and P (175 mg/m2). For enhanced bone safety the trial ...