Abstract 749P
Background
Luveltamab tazevibulin (luvelta) is a novel FRα ADC targeting recurrent high-grade EOC with a broad level of FRα expression, showing promising antitumor activity. Published data indicate that combining bev with a FRα ADC may lead to improved clinical activity. We report dose escalation (DE) outcomes of the ongoing phase 1b trial (NCT05200364) evaluating safety and antitumor activity of luvelta + bev in patients (pts) with recurrent EOC.
Methods
Phase 1b open-label, modified 3+3 DE/dose expansion global study. Key eligibility include age ≥18 years, recurrent high-grade EOC, and ≥1 measurable lesion. Luvelta (3.5, 4.3, and 5.2 mg/kg) was administered IV Q3W with bev 15 mg/kg. FRα expression was determined retrospectively by IHC using tumor proportion score (TPS; proportion of cells expressing FRα at any intensity).
Results
As of 19 April 2024, 18 pts were enrolled in the DE cohorts; 17 discontinued. Median age was 63 years, median prior lines of therapy was 2.5 (range 1–6), with prior bev treatment in 56% pts. One pt (5.2 mg/kg) had 2 DLTs (G3 nausea and G4 decreased appetite). Most common TEAEs were neutropenia (72%), nausea (61%), arthralgia (61%), and constipation (56%); most common ≥G3 TEAEs were neutropenia (44%), confusional state (16.7%), sepsis, hypokalaemia and hyponatraemia (11.1% each). Febrile neutropenia occurred in 1 pt (5.6%). Two pts experienced G5 sepsis, one case possibly related to luvelta per Sponsor; safety management guidelines were updated. Five pts (27.8%) discontinued due to TEAEs. Table: 749P
Antitumor activity (per RECIST v1.1)
| All pts (N=17 ∗ ) | Bev naive (n=8) | Bev treated (n=9) | FRα TPS ConclusionsEncouraging antitumor activity was observed irrespective of FRa expression and prior bev treatment. This combination may offer a non-biomarker driven approach. Luvelta + bev had no new safety signals vs either alone. The expansion phase of the study is enrolling with selected luvelta dose 4.3 mg/kg. Clinical trial identificationNCT05200364. Editorial acknowledgementEditorial and medical writing support was provided by Sandra Mendes, PhD, CMPP, from Aptitude Health, The Hague, the Netherlands, and funded by Sutro Biopharma. Legal entity responsible for the studySutro Biopharma. FundingSutro Biopharma. DisclosureL.P. Martin: Financial Interests, Personal, Speaker, Consultant, Advisor: Sutro Biopharma, Inc, Elucida Oncology, Inc, ImmunoGen, Inc, Daiichi Sankyo, Inc. A. Madariaga: Financial Interests, Personal, Invited Speaker: MSD, Clovis, GSK, AstraZeneca; Financial Interests, Personal, Advisory Board: PharmaMar, GSK, AstraZeneca; Non-Financial Interests, Member, Chair Young Investigators Gynecology Cancer Group: EORTC. A.I. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines; Financial Interests, Personal, Other, Consulting or Advisory Role / Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: Next Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Local PI: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Kezar, Revolution Med. A. Oaknin: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, F. Hoffmann-La Roche, GSK, Genmab, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Novocure, OncoXerna Therapeutics, Inc, PharmaMar, Regeneron, Shattuck Labs, Seagen/Pfizer, Sutro Biopharma, Exelisis, Daiichi Sankyo, Debiopharm International, Myriad Genetics, Zentalis; 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. R. Schilder: Financial Interests, Personal, Speaker, Consultant, Advisor: Celsion, Incyte, Eisai. E.M. Guerra Alia: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca-MSD, Clovis Oncology, GSK/Tesaro, PharmaMar, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca-MSD, PharmaMar, Roche, GSK/Tesaro; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Roche, GSK/Tesaro, Baxter. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, Olema Pharmaceuticals, Stemline Therapeutics, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Other, Consulting: Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Jefferies LLC, Medical Pharma Services, Tempus Labs, Zentalis Pharmaceuticals; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Dana Farber Cancer Inst, Hutchinson MediPharma, MedImmune, Seagen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, AbbVie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, ImmunoGen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses Pharma, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Artios, BeiGene, Bliss BioPharmaceuticals, Cascadian Therapeutics, Context Therapeutics, Cullinan, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetic Laboratories, Silverback Therapeutics, Stemline Therapeutics. R..W. Naumann: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme, AstraZeneca, Eisai, Bristol Myers Squibb, Seagen, Agenus, Sutro Biopharma, GOG Partners, GSK/Tesaro, Genelux, Laekna Therapeutics, ImmunoGen, EMD Serono; Financial Interests, Personal, Speaker’s Bureau: Seagen; Financial Interests, Institutional, Research Funding: BMS, OncoMed, Sutro Biopharma, Gynecologic Oncology Group, Mersana, GSK/Tesaro. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, ImmunoGen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, ImmunoGen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, ImmunoGen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, Roche, Incyte; Non-Financial Interests, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Non-Financial Interests, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Member, Board of Directors: GCIG; Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK. L. Lu: Financial Interests, Personal, Full or part-time Employment: Sutro Bio; Financial Interests, Personal, Stocks/Shares: Sutro Bio. C.J. Berman: Financial Interests, Personal, Full or part-time Employment: Sutro Bio; Financial Interests, Personal, Stocks/Shares: Sutro Bio. A.E. Borgman: Financial Interests, Personal, Full or part-time Employment: Sutro Bio; Financial Interests, Personal, Stocks/Shares: Sutro Bio. J.W. Moroney: Financial Interests, Institutional, Research Funding: Merck, ArsenalBio, Amgen, Regeneron, Acrivon, ImmunoGen, Genentech, Sutro Bio, Verastem. All other authors have declared no conflicts of interest. 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