A phase 1b dose escalation study of ipafricept (OMP—54F28) in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer Journal Article

   

Authors:	Moore, K. N.; Gunderson, C. C.; Sabbatini, P.; McMeekin, D. S.; Mantia-Smaldone, G.; Burger, R. A.; Morgan, M. A.; Kapoun, A. M.; Brachmann, R. K.; Stagg, R.; Farooki, A.; O'Cearbhaill, R. E.
Article Title:	A phase 1b dose escalation study of ipafricept (OMP—54F28) in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer
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 = 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. © 2019 Elsevier Inc.
Keywords:	ovarian cancer; wnt signaling; ipafricept; platinum sensitive
Journal Title:	Gynecologic Oncology
Volume:	154
Issue:	2
ISSN:	0090-8258
Publisher:	Elsevier Inc.
Date Published:	2019-08-01
Start Page:	294
End Page:	301
Language:	English
DOI:	10.1016/j.ygyno.2019.04.001
PUBMED:	31174889
PROVIDER:	scopus
PMCID:	PMC7397408
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85066448245&doi=10.1016%2fj.ygyno.2019.04.001&partnerID=40&md5=89914b8d40c6c98350a40068a44649eb
Notes:	Article -- Export Date: 2 August 2019 -- Source: Scopus

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