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Moore KN , Gunderson CC , Sabbatini P , McMeekin DS , Mantia-Smaldone G , Burger RA , Morgan MA , Kapoun AM , Brachmann RK , Stagg R , Farooki A , O'Cearbhaill RE
A phase 1b dose escalation study of ipafricept (OMP54F28) in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer
Gynecol Oncol. 2019 Aug;154(2) :294-301
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Abstract
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=5mg/ml.min) and P (175mg/m(2)). 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 & 4mg/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 6mg/kg. The overall response rate (ORR) was 75.7%. Median PFS was 10.3months (95% CI 8.5-14.2) and OS 33months (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.
Notes
1095-6859 Moore, Kathleen N Gunderson, Camille C Sabbatini, Paul McMeekin, D Scott Mantia-Smaldone, Gina Burger, Robert A Morgan, Mark A Kapoun, Ann M Brachmann, Rainer Karl Stagg, Robert Farooki, Azeez O'Cearbhaill, Roisin E P30 CA008748/CA/NCI NIH HHS/United States Journal Article United States Gynecol Oncol. 2019 Aug;154(2):294-301. doi: 10.1016/j.ygyno.2019.04.001. Epub 2019 Jun 4.