Introduction/Background Favezelimab, an anti-lymphocyte-activation gene 3 antibody, plus the anti-PD-1 antibody pembrolizumab, has shown promising antitumour activity in early-phase studies. MK-4280A is a coformulation of a fixed-dose combination of favezelimab+pembrolizumab. Pembrolizumab+lenvatinib is a standard treatment for previously treated advanced endometrial cancer (EC) that is mismatch repair-proficient (pMMR) in patients who are not candidates for surgery or radiation, based on results from the KEYNOTE-775 study. We describe cohort B of the MK-4280A-010 study (NCT06036836) evaluating MK-4280A+lenvatinib vs pembrolizumab+lenvatinib in previously treated pMMR advanced EC.

Methodology Cohort B of this phase 2, randomised, double-blind study is enrolling patients aged ≥18 years with histologically confirmed stage IVB (per FIGO 2009 staging) recurrent/metastatic EC with PD after 1 prior line of platinum-based chemotherapy (any setting; or 2 prior lines if 1 regimen received in neoadjuvant/adjuvant setting) and no prior anti-PD-(L)1 therapy. Patients must have measurable disease per RECIST v1.1 by investigator review, tumours with pMMR status per local testing, and must not be candidates for curative surgery or radiation. Approximately 80 patients (40/arm) will be randomised 1:1 (stratification: histology [nonendometrioid vs endometrioid]; prior therapy [adjuvant only vs treatment in metastatic setting]) to receive MK-4280A (favezelimab 800 mg with pembrolizumab 200 mg) IV Q3W + lenvatinib 20 mg orally QD or pembrolizumab 200 mg IV Q3W + lenvatinib 20 mg orally QD. Treatment will continue for ≤35 cycles (lenvatinib may continue for >2 years in patients experiencing clinical benefit), or until PD or intolerable toxicity. Imaging occurs at weeks 6 and 12 from start of study treatment and Q9W thereafter. AEs are assessed throughout the study and graded per NCI CTCAE v5.0. Primary endpoint is ORR per RECIST v1.1 by investigator assessment. Secondary endpoints are OS; PFS and duration of response per RECIST v1.1 by investigator assessment; and safety. Enrolment began in September 2023.

Results TBD

Conclusion TBD

Disclosures Toon Van Gorp: Grants/research funding: AstraZeneca, Roche, Amgen; Honoraria/consultation fees: AstraZeneca, Eisai, GSK, MSD, ImmunoGen, Incyte, OncXerna Therapeutics, Seagen Tubulis, Zentalis; Speaker’s bureau: AstraZeneca, GSK, ImmunoGen; Other support: AstraZeneca, GSK, ImmunoGen, MSD, PharmaMar, Roche (travel, accommodation, expenses). Vicky Makker:

Grants/research funding: AstraZeneca (Inst), Bayer (Inst), Bristol-Myers Squibb (Inst), Clovis Oncology (Inst), Duality (Inst), Eisai (Inst), Faeth Therapeutics (Inst), Karyopharm Therapeutics (Inst), Lilly (Inst), Merck (Inst), Takeda (Inst), Zymeworks (Inst), Cullinan (Inst); Honoraria/consultation fees: AstraZeneca, Clovis Oncology, Cullinan, Duality, Eisai, Faeth Therapeutics, GlaxoSmithKline, Jazz, Immunocore, ITeos Therapeutics, Kartos Therapeutics, Karyopharm Therapeutics, Lilly, Merck, Moreo, Morphosys, Prelude, Novartis, Takeda, Zymeworks; Other support: Eisai, Merck (Travel, Accommodations, Expenses).

Christian Marth: Honoraria/consultation fees: Roche, Novartis, Amgen, MSD, PharmaMar, AstraZeneca, GSK, Seagen.

Eugenia Girda: Advisory board: Merck.

Mansoor Raza Mirza: Chief Oncologist: Dept. of Oncology, Rigshospitalet, Copenhagen University Hospital, Denmark; Medical Director: NSGO-CTU (Nordic Society of Gynaecological Oncology); Chairman2020–2022: ENGOT (European Network of Gynaecological Oncology Trials group); Vice-President: ESGO (European Society of Gynaecological Oncology); Faculty: ESMO (European Society of Medical Oncology); Advisory board: Allarity Therapeutics, Astra Zeneca, Biocad, Biontech, Boehringer Ingelheim, Clovis, Daiichi-Sankyo, Eisai, Genmab, GSK, Immunogen, Incyte, Karyopharm, Merck/MSD, Mersana, Novartis, Regeneron, Roche, SeaGen, Takeda, Tesaro, Zailab; Member of board of directors, stocks/shares: Karyopharm Therapeutics, Sera Prognostics; Research grant: Allarity, Apexigen, Astra Zeneca, Boehringer Ingelheim, Clovis, GSK, Novartis, Tesaro, Ultimovacs; Trial chair: AstraZeneca, Boehringer Ingelheim, Deciphera, Daiichi-Sankyo, GSK, Merck, Mersana, NuvationBio, Tesaro.

Ronnie Shapira Frommer: Research grant to institution: Merck Sharp and Dohme; Speaker honoraria: Bristol Myers Squibb, Merck Sharp and Dohme, Novartis, Sanofi, Roche, Medison, Neopharm; Advisory board: Merck Sharp and Dohme, VBL therapeutics, Clovis Oncology

Leah Suttner: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock in Merck & Co., Inc., Rahway, NJ, USA.

Roman Groisberg: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock in Merck & Co., Inc., Rahway, NJ, USA.

Fan Jin: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock in Merck & Co., Inc., Rahway, NJ, USA.

David M. O’Malley: Grants/research funding: AbbVie, Advaxis, Agenus,Inc, Alkermes, Aravive, Inc., Arcus Biosciences, Inc., AstraZeneca, BeiGene USA,Inc., Boston Biomedical, Bristol Myers Squibb, Clovis Oncology, Deciphera Pharma, Eisai, EMD Serono, Inc., Exelixis, Genentech Inc, Genmab, GlaxoSmithKline, GOG Foundation, Hoffmann-La Roche Inc., ImmunoGen, Inc., Incyte Corporation, IOVANCE Biotherapeutics, Karyopharm, Leap Therapeutics, Inc., Ludwig Institute for Ca, Merck & Co, Merck Sharp & Dohme Corp., Mersana Therapeutics, Inc., NCI, Novartis, NovoCure, NRG Oncology, OncoC4, Inc., OncoQuest Inc., Pfizer Inc, Precision Therapeutics, Inc., Prelude Therapeutics, Regeneron Pharmaceuticals, Inc, RTOG, Rubius Therapeutics, Seattle Genetics (SeaGen), Sutro Biopharma, SWOG, TESARO, Verastem, Inc; Honoraria/consultation fees: AbbVie, AdaptImmune, Agenus,Inc, Arquer Diagnostics, Arcus Biosciences, Inc., AstraZeneca, Atossa Therapeutics, Boston Biomedical, Cardiff Oncology, Celcuity, Clovis Oncology, Corcept Therapeutics, Duality Bio, Eisai, Elevar, Exelixis, Genentech Inc, Genelux, GlaxoSmithKline, GOG Foundation, Hoffmann-La Roche Inc, ImmunoGen, Inc, Imvax, InterVenn, INXMED, IOVANCE Biotherapeutics, Janssen, Jazz Pharmaceuticals, Laekna, Leap Therapeutics, Inc., Luzsana Biotechology, Merck & Co, Merck Sharp & Dohme Corp., Mersana Therapeutics,Inc., Myriad, Novartis, NovoCure, OncoC4, Inc., Onconova, Regeneron Pharmaceuticals, Inc, RepImmune, R Pharm, Roche Diagnostics, Seattle Genetics (SeaGen), Sorrento, Sutro Biopharma, Tarveda Therapeutics, Toray, Trillium, Umoja, Verastem, Inc, VBL Therapeutics,Vincerx Pharma, Xencor, Zentalis.