A phase 1 dose escalation and expansion study of Tarextumab (OMP-59R5) in patients with solid tumors

• DOI: 10.1007/s10637-018-0714-6
• Publication Date: 2018-12-28T02:30:07Z
• Authors: David C. Smith; Rashmi Chugh; Amita Patnaik; Kyriakos P. Papad...; Min Wang; Ann M. Kapoun; Lu Xu; Jakob Dupont; Robert J. Stagg; Anthony Tolcher
• Keywords: Pharmacodynamics; Anorexia

Summary Purpose This Phase I trial evaluated the maximum tolerated dose, safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of tarextumab (OMP-5948), a novel cross-reactive antibody which binds selectively inhibits signaling via both Notch2 Notch3, in adult patients with advanced malignancies. Methods Standard 3 + design 0.5, 1, 2.5, or 5 mg/kg weekly, 5, 7.5, 10 every other week, 7.5 mg weeks. Dose-limiting toxicities (DLT) were assessed during first 28 days. Results Forty-two received (21 15 6 three weeks). 2/6 subjects at weekly 2/3 0/6 weeks had DLT. The dose (MTD) was 2.5 on week schedules. Gastrointestinal (GI) toxicity most common adverse event diarrhea (81%), fatigue (48%), nausea (45%), anorexia (38%), vomiting (38%) abdominal pain constipation (24% each). Biomarker analysis showed regulation stem cell Notch gene signaling. Conclusion Tarextumab generally well-tolerated doses < third week. Diarrhea dose-limiting above these levels, but relatively easily managed lower doses. Inhibition pathway demonstrated ClinicalTrials.gov Identifier: NCT01277146.