A phase I/II study of rovalpituzumab tesirine in delta-like 3-expressing advanced solid tumors.
NPJ Precis Oncol
oregon; portland; chiles
Delta-like protein 3 (DLL3) is highly expressed in solid tumors, including neuroendocrine carcinomas/neuroendocrine tumors (NEC/NET). Rovalpituzumab tesirine (Rova-T) is a DLL3-targeting antibody-drug conjugate. Patients with NECs and other advanced DLL3-expressing tumors were enrolled in this phase I/II study (NCT02709889). The primary endpoint was safety. Two hundred patients were enrolled: 101 with NEC/NET (large-cell NEC, gastroenteropancreatic NEC, neuroendocrine prostate cancer, and other NEC/NET) and 99 with other solid tumors (melanoma, medullary thyroid cancer [MTC], glioblastoma, and other). The recommended phase II dose (RP2D) was 0.3 mg/kg every 6 weeks (q6w) for two cycles. At the RP2D, grade 3/4 adverse events included anemia (17%), thrombocytopenia (15%), and elevated aspartate aminotransferase (8%). Responses were confirmed in 15/145 patients (10%) treated at 0.3 mg/kg, including 9/69 patients (13%) with NEC/NET. Rova-T at 0.3 mg/kg q6w had manageable toxicity, with antitumor activity observed in patients with NEC/NET, melanoma, MTC, and glioblastoma.
Earle A. Chiles Research Institute
Mansfield, Aaron S; Hong, David S; Hann, Christine L; Farago, Anna F; Beltran, Himisha; Waqar, Saiama N; Hendifar, Andrew E; Anthony, Lowell B; Taylor, Matthew H; Bryce, Alan H; Tagawa, Scott T; Lewis, Karl; Niu, Jiaxin; Chung, Christine H; Cleary, James M; Rossi, Michael; Ludwig, Carrianne; Valenzuela, Ricardo; Luo, Yan; and Aggarwal, Rahul, "A phase I/II study of rovalpituzumab tesirine in delta-like 3-expressing advanced solid tumors." (2021). Articles, Abstracts, and Reports. 5200.