741MO - Luveltamab tazevibulin (STRO-002), an anti-folate receptor alpha (FolRα) antibody drug conjugate (ADC), demonstrates clinical activity in recurrent/progressive epithelial endometrial cancer (EEC): STRO-002-GM1 phase I dose expansion

Background

Luveltamab tazevibulin (luvelta) is a novel FolRα-targeting ADC with a stable cleavable linker and a 3-aminophenyl hemiasterlin warhead (DAR 4) that induces cytotoxic and immunogenic cell death. Using site-specific conjugation technology and proprietary cell-free protein synthesis platform, luvelta is designed to target a broad range of FolRα expressing cancers, including EEC.

Methods

Following completion of the STRO-002-GM1 phase 1 study, a dose expansion cohort was enrolled consisting of metastatic EEC with progression after ≥ 1 platinum or immunotherapy-based regimen (≤ 3 total lines) with ≥ 1% FolRα expression (any intensity using Ventana FolR1 IHC assay). Luvelta dose was 5.2 mg/kg q3w. In patients (pts) with prior pelvic irradiation, a dose of 4.3 mg/kg q3w was administered. The primary endpoint is objective response rate (RECIST v1.1) with secondary endpoints of safety and PK.

Results

17 pts were enrolled (8 pts at 5.2 mg/kg and 9 pts at 4.3 mg/kg). Prior therapy: median lines=2; prior platinum=17 pts; and prior PD-1=4 pts. Median exposure was 12 weeks (range 3-38). Initial efficacy data is presented in the table. Table: 741MO

Best response (RECIST v1.1)

The safety profile was consistent with prior reported data in ovarian cancer pts treated with luvelta. The most common Grade 3 or higher (G3+) adverse events (AEs) were neutropenia (53%), anemia (24%), and arthralgia(18%). There were no G3 eye disorder AEs, 1 G3+ pulmonary AE (G3 COVID pneumonia) and no G5 AEs. A single pt had an AE leading to discontinuation (G3 arthralgia).

Conclusions

Advanced EEC remains an area of high unmet need with a poor prognosis and limited treatment options. Preliminary data indicate that luvelta has a predictable and manageable safety profile with encouraging clinical activity in pts with recurrent/progressive FolRα expressing EEC. Luvelta warrants further development as a targeted agent for EEC.

Clinical trial identification

NCT03748186.

Editorial acknowledgement

Legal entity responsible for the study

Sutro Biopharma, Inc.

Funding

Sutro Biopharma, Inc.

Disclosure

B. Pothuri: Financial Interests, Personal, Advisory Board, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board, Advisory board: AstraZeneca; Financial Interests, Personal, Advisory Board: Clovis Oncology, GSK, Merck, Tesaro, Sutro, Mersana, Lily, Seattle Genetics; Financial Interests, Personal, Other, consulting: Toray, Arquer Diagnostics, Atossa, Elevar, Deciphera, Imab; Financial Interests, Institutional, Local PI: Tesaro, Clovis Oncology, Roche Genentech, Takeda, Celsion, Celgene, AstraZeneca, Immunogen, Merck, GSK; Financial Interests, Institutional, Local PI, clinical trial: Incyte, Toray, Karyopharm, Sutro, Eisai, VBL Therapeutics, Mersana, Seattle Genetics; Non-Financial Interests, Other, Member of GOG Partners group: GOG Foundation; Non-Financial Interests, Member of Board of Directors: Society of Gynecologic Oncology. R.W. Naumann: Financial Interests, Personal, Advisory Role: Merck Sharp and Dohme, AstraZeneca, Clovis Oncology, OncoMed, Eisai, Bristol Myers Squibb, Seagen, Agenus, Sutro Biopharma, Inc., GOG Partners, GSK/Tesaro, Genelux, Laekna; Financial Interests, Personal, Invited Speaker: Seagen ; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, OncoMed, Sutro Biopharm, Inc., Gynecology Oncology Group, Mersana, GSK/Tesaro. L.P. Martin: Financial Interests, Personal, Advisory Role: Sutro Biopharma, Inc., Elucida Oncology, Immunogen, Myriad Genetics; Financial Interests, Personal, Research Funding: Agenus, AstraZeneca, Sutro Biopharma, Inc., Immunogen. D. O'Malley: Financial Interests, Institutional, Research Funding: AbbVie, Advaxis, Agenus, Alkemes, Aravive, Arcus Biosciences, AstraZeneca, BeiGene, Boston Biomedical, Bristol Squibb Myers, Clovis Oncology, Deciphera Pharma, Eisai, EMD Serono, Exelixis, Genentech, Inc., Genmab, GSK, GOG Foundation , F. Hoffmann-La Roche, Inc., Immunogen, Incyte Corporation, Iovance Biotherapeutics, Karyopharm, Leap Therapeutics, Inc., Ludwig Institute for Cancer, Merck and Co, Merck Sharp and Dohme, Mersana, NCI, Novartis, NovoCure, NRG Oncology, OncoC4, Inc., OncoQuest, Inc., Pfizer, Precision Therapeutics, Prelude Therapeutics, Regeneron Pharmaceuticals, Inc., RTOG, Rubius Therapeutics, Seattle Genetics, SWOG, Tesaro; Financial Interests, Personal, Advisory Role: AbbVie, Adaptimmune, Agenus, Arquer Diagnostics, Arcus Biosciences, AstraZeneca, Atossa Therapeutics, Boston Biomedical, Cardiff Oncology, Celcuity, Clovis Oncology, Corcept, Duality Bio, Eisai, Elevar, Exelixis, Genentech, Inc., Genelux, GSK, GOG Foundation, F. Hoffmann-La Roche, Inc., Immunogen, Inc., Imvax, InterVenn, INXMED, Iovance Therapeutics, Jannsen, Jazz Pharmaceuticals, Laekna, Leap Therapeutics, Luzsana Biotechnology, Merck and Co, Merck Sharpe and Dohme, Mersana, Myriad, Novartis, NovoCure, OncoC4, Inc., Onconova, Regeneron Pharmaceuticals, Repimmune, R Pharm, Roche Diagnostics, Seattle Genetics, Sorrento, Tarveda Therapeutics, Toray, Trillium, Umoja, Verastem, Inc., VBL Therapeutics, Vincerx Pharma, Xenocor, Zentalis; Financial Interests, Personal, Advisory Board: Sutro Biopharm, Inc. J.W. Moroney: Financial Interests, Institutional, Research Funding: Sutro Biopharma, Inc. J. Garcia-Donas: Financial Interests, Institutional, Research Funding: Sutro Biopharma. A. Redondo Sanchez: Financial Interests, Institutional, Research Funding: Sutro Biopharma, Inc. 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. D.G. Illescas: Financial Interests, Institutional, Research Funding: Sutro Biopharma, Inc. L. Liu: Financial Interests, Personal, Full or part-time Employment: Sutro Biopharma, Inc. C. Berman: Financial Interests, Personal, Full or part-time Employment, Employee: 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. All other authors have declared no conflicts of interest.