Efficacy and safety of luveltamab tazevibulin vs investigator’s choice of chemotherapy in patients with recurrent platinum-resistant ovarian cancer (PROC) expressing folate receptor alpha (FRα): The REFRaME-01 (GOG-3086, ENGOT-79ov, and APGOT-OV9) phase 2/3 study.

Ana Oaknin Medical Oncology Service, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain info_outline Ana Oaknin, Jung-Yun Lee, David Cibula, Yeh Chen Lee, Russell J. Schilder, Annika Auranen, Bo Gao, David Shao Peng Tan, Amit M. Oza, Rowan Miller, Vanda Salutari, Giulia Tasca, David M. O'Malley, Bradley J. Monk, Bhavana Pothuri, Lin Lu, Craig Berman, Anne Borgman, R. Wendel Naumann

Authors Ana Oaknin Medical Oncology Service, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain info_outline Ana Oaknin, Jung-Yun Lee, David Cibula, Yeh Chen Lee, Russell J. Schilder, Annika Auranen, Bo Gao, David Shao Peng Tan, Amit M. Oza, Rowan Miller, Vanda Salutari, Giulia Tasca, David M. O'Malley, Bradley J. Monk, Bhavana Pothuri, Lin Lu, Craig Berman, Anne Borgman, R. Wendel Naumann Organizations Medical Oncology Service, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, Yonsei Cancer Center and Severance Hospital, Seoul, South Korea, Department of Gynaecology, Obstetrics and Neonatology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic, The Royal Hospital for Women, Sydney, Australia, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA, Tampere University Hospital, Tays Cancer Centre and Nordic Society of Gynaecological Oncology (NSGO), Tampere, Finland, Blacktown and Westmead Hospitals, Westmead, Australia, Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore, Princess Margaret Cancer Centre, Toronto, ON, Canada, University College London and St. Barts Hospitals, London, United Kingdom, Policlinico Universitario Fondazione Agostino Gemelli, IRCCS, Rome, Italy, Veneto Institute of Oncology IOV–IRCCS, Padua, Italy, The Ohio State University and James Comprehensive Cancer Center, Columbus, OH, Florida Cancer Specialists and Research Institute, West Palm Beach, FL, Perlmutter Cancer Center, NYU Langone Health, New York, NY, Sutro Biopharma, Inc., South San Francisco, CA, Sutro Biopharma, South San Francisco, CA, Levine Cancer Atrium Health, Charlotte, NC Abstract Disclosures Research Funding Sutro Biopharma Background: The treatment of recurrent epithelial ovarian cancer remains a challenge, particularly for tumors with low to moderate expression levels of FRα. Luveltamab tazevibulin (luvelta) is an anti–FRα-targeting antibody-drug conjugate with a stable cleavable linker and a 3-aminophenyl hemiasterlin warhead (DAR=4), which induces cytotoxic and immunologic cell death. Luvelta was designed to treat multiple cancers with a broad range of FRα expression. Luvelta demonstrated preliminary antitumor activity in women with recurrent ovarian cancer, selected for FRα expression level of ≥25% at any intensity (tumor proportion score [TPS]). In PROC, this cutoff represents an estimated 80% of patients (pts). In a phase 1 study of luvelta in relapsed ovarian cancer, the overall response rate (ORR) was 37.5% with a median duration of response (DOR) of 5.5 months and a median progression-free survival (PFS) of 6.1 months. ORR was higher at 5.2 mg/kg compared with 4.3 mg/kg (43.8% vs 31.3%). The safety profile was manageable, with the most common grade ≥3 adverse events consisting of neutropenia, arthralgia, and anemia (Oaknin et al. J Clin Oncol 2023;41[16 suppl]:5508). These results support further investigation in pts with PROC whose tumors have a broad range of FRα expression. Herein, we describe a phase 2/3 pivotal study (REFRaME-01)of luvelta in this pt population. Methods: This randomized, global, open-label, 2-part phase 2/3 pivotal study has been designed to assess the efficacy and safety of luvelta vs investigator’s choice (IC) chemotherapy in pts with recurrent PROC expressing FRα (NCT05870748). Eligible pts are adults (≥18 years) with relapsed PROC, 1–3 prior lines of therapy (which must include bevacizumab), measurable disease, Eastern Cooperative Oncology Group performance status ≤1, and TPS for FRα expression ≥25% using Ventana validated IHC assay. Part 1 (phase 2) consists of a luvelta dose-optimization stage in which pts are randomized 1:1 to receive intravenous (IV) luvelta every 3 weeks (Q3W) at 4.3 mg/kg or IV luvelta Q3W at 5.2 mg/kg with prophylactic G-CSF for 2 cycles followed by 4.3 mg/kg luvelta from cycle 3 onward. Part 1 data will be used to select the optimal dosing regimen. In part 2 (phase 3) ~550 pts will be enrolled and randomized 1:1 to the optimal luvelta dosing regimen or IC chemotherapy (gemcitabine, paclitaxel, pegylated liposomal doxorubicin, or topotecan). Primary endpoints are PFS and ORR, with response evaluated per RECIST v1.1. Secondary endpoints include overall survival, DOR, safety, and quality of life. Clinical trial information: NCT05870748.

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