A phase I/II study of rovalpituzumab tesirine in delta-like 3-expressing advanced solid tumors

Aaron S Mansfield; David S Hong; Christine L Hann; Anna F Farago; Himisha Beltran; Saiama N Waqar; Andrew E Hendifar; Lowell B Anthony; Matthew H Taylor; Alan H Bryce; Scott T Tagawa; Karl Lewis; Jiaxin Niu; Christine H Chung; James M Cleary; Michael Rossi; Carrianne Ludwig; Ricardo Valenzuela; Yan Luo; Rahul Aggarwal

doi:10.1038/s41698-021-00214-y

A phase I/II study of rovalpituzumab tesirine in delta-like 3-expressing advanced solid tumors

NPJ Precis Oncol. 2021 Aug 5;5(1):74. doi: 10.1038/s41698-021-00214-y.

Authors

Aaron S Mansfield¹, David S Hong², Christine L Hann³, Anna F Farago⁴, Himisha Beltran⁵, Saiama N Waqar⁶, Andrew E Hendifar⁷, Lowell B Anthony⁸, Matthew H Taylor⁹, Alan H Bryce¹⁰, Scott T Tagawa¹¹, Karl Lewis¹², Jiaxin Niu¹³, Christine H Chung¹⁴, James M Cleary⁵, Michael Rossi¹⁵, Carrianne Ludwig¹⁵, Ricardo Valenzuela¹⁵, Yan Luo¹⁵, Rahul Aggarwal¹⁶

Affiliations

¹ Mayo Clinic, Rochester, MN, USA.
² The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³ Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
⁴ Massachusetts General Hospital, Boston, MA, USA.
⁵ Dana-Farber Cancer Institute, Boston, MA, USA.
⁶ Washington University School of Medicine, St. Louis, MO, USA.
⁷ Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁸ University of Kentucky Chandler Medical Center, Lexington, KY, USA.
⁹ Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
¹⁰ Mayo Clinic, Phoenix, AZ, USA.
¹¹ Weill Cornell Medicine, New York, NY, USA.
¹² University of Colorado Denver, Aurora, CO, USA.
¹³ Banner MD Anderson Cancer Center, Gilbert, AZ, USA.
¹⁴ H Lee Moffitt Cancer Center, Tampa, FL, USA.
¹⁵ AbbVie, Inc, North Chicago, IL, USA.
¹⁶ UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. Rahul.Aggarwal@ucsf.edu.

Abstract

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.