818TiP - REFRaME-O1/ENGOT-OV79/GOG-3086: A phase II/III open-label study evaluating the efficacy and safety of luveltamab tazevibulin versus investigator’s choice of chemotherapy in women with relapsed platinum-resistant epithelial ovarian cancer expressing folate receptor alpha (FolRα)

Background

Folate receptor alpha (FolRα) is a validated target in the treatment of platinum resistant ovarian cancer (PROC) with high FolRα expression. There continues to be a high unmet need to treat PROC with low to moderate expression levels of FolRα. Luveltamab tazevibulin (luvelta) is a novel FolRα targeting ADC, with a stable cleavable linker and a 3-aminophenyl hemiasterlin warhead (DAR4) that induces cytotoxic and immunogenic cell death. Luvelta is generated using cell free antibody production and site-specific conjugation technology and is designed to target a broad range of FolRα expressing cancers. Luvelta demonstrated preliminary efficacy data (ORR of 37.5%; mDOR of 5.5 months; mPFS of 6.1 months) in 32 patients with advanced relapsed EOC who had FolRα expression of >25% of any intensity in a phase 1 study STRO-002-GM1 (NCT03748186). Sub-analysis demonstrated a higher ORR at 5.2 mg/kg (43.8% versus 31.3%, n=32) compared to 4.3 mg/kg. The safety profile was shown to be manageable, with the most common grade 3 and higher adverse events consisting of neutropenia, arthralgia, and anemia. This data forms the basis for a pivotal study of luvelta in patients with PROC whose tumors express a broad level of FolRα expression.

Trial design

REFRaME-O1 is a multicenter, international, open-label, 2-part seamless phase 2/3 study of luvelta in subjects with relapsed PROC expressing FolRα. Part 1 consists of a dose-optimization stage and will randomize ∼50 subjects 1:1 to the treatment of luvelta at 4.3 mg/kg Q3W or luvelta 5.2 mg/kg Q3W + prophylactic pegfilgrastim for 2 cycles followed by 4.3 mg/kg Q3W. Part 2 will commence with the selected optimized dose and will include a control arm consisting of investigator’s choice chemotherapy, with a 2:1 randomization schedule. Key inclusion criteria are progressive PROC, up to 3 prior regimens, TPS of ≥25% for FolRα expression, and measurable disease. Key exclusion criteria are primary platinum refractory disease and prior treatment with a FolRα ADC or ADC containing a tubulin inhibitor.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Sutro Biopharma, Inc.

Funding

Sutro Biopharma, Inc.

Disclosure

R.W. Naumann: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, AstraZeneca, Clovis Oncology, OncoMed, Eisai, BMS, Seagen, Agenus, Sutro Biopharma, GOG Partners, GSK/Tesaro, Genelux, Laekna, Immunogen. A. Gonzalez Martin: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Clovis, GSK, Genmab, Alkermes, Sutro, Roche, SOTIO, PharmaMar, Oncoinvent, Novartis, Mersana, MSD, Macrogenics, Eisai, Inmunogen, Regeneron, HederaDx, Illumina; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, Clovis, Roche, Novocure, MSD, Takeda, Zaylab; Financial Interests, Institutional, Coordinating PI, PI of ANITA trial: GSK, Roche; Financial Interests, Personal, Steering Committee Member, Member of ENGOT ov43-SC: MSD; Financial Interests, Institutional, Coordinating PI, ENGOT PI of EPIK-O trial: Novartis; Financial Interests, Institutional, Coordinating PI, ENGOT PI of AVB-500 phase III trial: Aravive. T.J. Herzog: Financial Interests, Personal, Advisory Board: Sutro Biopharma. R.L. Coleman: Financial Interests, Personal, Advisory Board: AstraZeneca, Agenus, Alkermes, Immunogen, Roche/Genentech, GSK, Genmab/Seagen, Epsilogen, Myriad Genetics; Financial Interests, Personal, Invited Speaker: AstraZeneca, Genmab/Seagen; Non-Financial Interests, Principal Investigator: AbbVie, immunogen, Roche/Genentech, Merck, Genmab, clovis; Non-Financial Interests, Project Lead, MyLung Consortium: US Oncology Research. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, SUTRO, BMS, Adaptimmune, Daiichi Sankyo; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: GINECO. R. Miller: Financial Interests, Personal, Advisory Board: GSK, AZD, Merck, Shionogi, Ellipses; Financial Interests, Personal, Invited Speaker: GSK, AZD, Clovis Oncology. L. Lu, H. Dokainish, C. Berman: Financial Interests, Personal, Stocks/Shares: Sutro Biopharma. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche, Seagen, OneXerna Therapeutics, Inc., Regeneron, Sutro Biopharma; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Amgen, AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Aprea Therapeutics AB, Regeneron Pharmaceuticals, Clovis Oncology Inc., EISAI limited Ltd., F. Hoffmann-La Roche Ltd., Immunogen Inc., Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc., PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019 . Scientific Track Member Gynaecological Cancers ESMO 2018 , ESMO 2020 , ESMO 2022 . Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines: ESMO; Non-Financial Interests, Leadership Role, ESMO GYN Co-Chair 2023-2025: ESMO; Non-Financial Interests, Leadership Role, Chair de Cervix Committee. 2022-2024: GCIG; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG.