A phase 1b dose escalation study of ipafricept (OMP[sbnd]54F28)in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer
Genital Diseases, Female
Genital Diseases, Male
© 2019 Objectives: The WNT pathway is an important oncologic driver of epithelial ovarian cancer (EOC). The first-in-class recombinant fusion protein ipafricept (IPA)blocks Wnt signaling through binding of Wnt ligands. This phase Ib trial was designed to determine the maximum tolerated dose (MTD)and recommended phase 2 dose (RPh2)for IPA in combination with taxane and platinum therapy (C/P). 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 was revised to 6-patient cohorts with a q3w regimen of IPA on Day 1 and C/P on Day 3 (IPA → C/P). Results: 37 patients have been treated; 30 of whom were treated following protocol revision to q3w IPA(D1)→ C/P(D3)(2 & 4 mg/kg). IPA-related TEAEs that occurred in ≥15% included: fatigue (40%); nausea (35%); diarrhea and decreased appetite (22%)each; dysgeusia (19%); and vomiting (16.2%). 22% reported ≥1 IPA related TEAE Grade ≥3 the most common of which was neutropenia at 16%. There were no DLTs; the MTD was not reached. The maximum administered dose based on bone safety was 6 mg/kg. The overall response rate (ORR)was 75.7%. Median PFS was 10.3 months (95% CI 8.5–14.2)and OS 33 months (95% CI 23.4-NR). Conclusions: IPA is well tolerated in combination with sequential C/P. ORR, PFS and OS are comparable to historical data but bone toxicity at efficacy doses of this particular Wnt inhibitor limit further development in EOC.
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