LBA28 - ENGOT-en11/GOG-3053/KEYNOTE-B21: A phase III study of pembrolizumab or placebo in combination with adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer

Background

Pembrolizumab (pembro) + chemotherapy (CTx) provides benefit as first-line therapy for advanced/recurrent endometrial cancer (EC), regardless of MMR status. The phase 3, randomized, double-blind ENGOT-en11/GOG-3053/KEYNOTE-B21 study (NCT04634877) evaluated pembro vs placebo (pbo) + adjuvant CTx (± radiation therapy [RT]) in patients (pts) with newly diagnosed, high-risk EC after surgery with curative intent.

Methods

Eligible pts were aged ≥18 y with newly diagnosed, histologically confirmed high-risk (FIGO stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology) EC following surgery with curative intent with no evidence of disease postoperatively. Pts had not received prior RT or systemic therapy. Pts were randomized to pembro 200 mg or pbo Q3W for 6 cycles + carboplatin-paclitaxel followed by pembro 400 mg or pbo Q6W for 6 cycles per treatment assignment. RT was at the investigator’s discretion and given after completion of CTx. Randomization was stratified by MMR status and, within pMMR, by planned RT, histology, and FIGO (2009) surgical stage. Primary endpoints were DFS per investigator and OS in the ITT population. The overall type I error rate was controlled at 2.5% (1-sided), with 2.5% initially allocated to test DFS superiority.

Results

1095 pts were randomized (pembro, n=545; pbo, n=550). At this interim analysis (data cutoff, Mar 4, 2024), there were 119 (22%) DFS events in the pembro arm and 121 (22%) in the pbo arm (HR, 1.02 [95% CI, 0.79−1.32]; P=0.570). Kaplan–Meier estimates of 2-year DFS rates were 75% and 76% in the pembro and pbo arms, respectively. HR for DFS was 0.31 (95% CI, 0.14−0.69) in the dMMR (n=281) subgroup and 1.20 (95% CI, 0.91−1.57) in the pMMR (n=814) subgroup. Grade ≥3 AEs occurred in 71% and 63% of pts in the pembro and pbo arms, respectively. No treatment-related grade 5 AEs occurred.

Conclusions

Adjuvant pembro + CTx did not improve DFS in pts with newly diagnosed, high-risk EC. In subgroup analyses, pembro + CTx led to clinically meaningful improvements in DFS in pts with dMMR tumors. Safety was manageable with no new safety signals.

Clinical trial identification

NCT04634877.

Editorial acknowledgement

Medical writing assistance was provided by Michael S. McNamara of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

T. Van Gorp: Financial Interests, Institutional, Advisory Board: AbbVie, BioNTech, ImmunoGen, Incyte, Karyopharm, Seagen, Zentalis; Financial Interests, Institutional, Advisory Board, Jan-2021 until 09-2022: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Eisai, ImmunoGen, MSD/Merck; Financial Interests, Institutional, Other, Travel costs: AstraZeneca, GSK, MSD/Merck, PharmaMar; Financial Interests, Institutional, Writing Engagement: Cancer Communications and Consultancy Ltd; Financial Interests, Institutional, Advisory Board, Jan-2021: Eisai; Financial Interests, Institutional, Advisory Board, May-2021 until present: GSK; Financial Interests, Institutional, Invited Speaker, Apr 2022: GSK; Financial Interests, Institutional, Advisory Board, Apr-2021 until present: MSD/Merck; Financial Interests, Institutional, Advisory Board, Feb-2021: OncXerna Therapeutics; Financial Interests, Institutional, Advisory Board, Feb 2023 until present: Tubulis; Financial Interests, Institutional, Research Grant, Oct-2020 until Oct-2021: Amgen; Financial Interests, Institutional, Research Grant, Oct-2020 until Oct-2022: Roche; Financial Interests, Institutional, Research Grant, Jan 2022 until Mar 2023: AstraZeneca; Non-Financial Interests, Leadership Role, Chair of BGOG (unremunerated): Belgian and Luxembourg Gynaecological Oncology Group (BGOG); Non-Financial Interests, Member of Board of Directors, Member of the strategic group (unremunerated): European Network for Gynaecological Oncological Trial groups (ENGOT). F. Backes: Financial Interests, Personal, Advisory Role: AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, GSK, ImmunoGen, Merck; Financial Interests, Institutional, Research Funding: Merck, Natera, AstraZeneca, Tempus, ImmunoGen; Financial Interests, Other, Travel: BioNTech, GSK. K. Hasegawa: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Takeda, Chugai, Genmab, Kaken, Eisai, Sanofi; Financial Interests, Personal, Advisory Board: GSK, Daiichi Sankyo, Terumo; Financial Interests, Institutional, Funding, contracted research: MSD, Ono, Daiichi Sankyo, Eisai, Takeda. S.H. Hietanen: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Orion, EISAI; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, GSK. A. Savarese: Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD, GSK; Financial Interests, Institutional, Research Funding: MSD, Glaxo, Mersana, PharmaMar; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Other, Accommodations and Travel: PharmaMar, MSD. Y.M. Kim: Financial Interests, Institutional, Research Funding, Institutional Financial Support to Clinical Studies: MSD, AstraZeneca, Roche, ImmunoGen, Genmab, Zentalis, BeiGene, Canaria Bio; Financial Interests, Other, Honorarium: MSD. L. Bodnar: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, pharma&, MSD; Financial Interests, Personal, Other, Personal Fees: AstraZeneca, Roche, GSK; Financial Interests, Personal, Research Funding: AstraZeneca, Roche, Novartis, MSD, Lilly, OncoQuest, Regeneron Pharmaceutical, Gilead, Amgen, Exelixis, Inc. M.P. Barretina Ginesta: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, MSD, Eisai, PharmaMar; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, MSD, Eisai; Financial Interests, Personal, Steering Committee Member: MSD. L. Gilbert: Financial Interests, Institutional, Research Grant: IMV, Pfizer, Sutro Bio, Pharma, MSD, Corcept Therapeutics, ImmunoGen, Shattuck Labs, Roche, Tesaro, K-Group Beta Inc., GOG Foundation, GSK, AstraZeneca, OncoQuest Pharmaceuticals, Novocure GmbH, Alkermes Inc, Espersas, Mersana; Financial Interests, Personal, Other, Consulting fees: MSD, GSK; Financial Interests, Personal, Other, Presentations, Lectures: MSD, GSK; Financial Interests, Personal, Other, Support for attending meetings and/or travel: GSK, MSD, Roche, Zentalis; Financial Interests, Personal, Advisory Board: GSK, MSD, Eisai, Novocure, Kora Health, Corcept, ImmunoGen, Canariabio Inc., Repare Therapeutics. B. Pothuri: Financial Interests, Institutional, Research Grant: AstraZeneca, Celsion, Clovis Oncology, Duality Bio, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Onconova, Seagen, Sutro Biopharma, Takeda Pharmaceuticals, Tesaro/GSK, Toray, VBL Therapeutics; Financial Interests, Personal, Other, Consulting Fees: AstraZeneca, BioNtech, Clovis Oncology, Eisai, GOG-Foundation, Lily, Merck, Mersana, Onconova, Sutro Biopharma, Tesaro/GSK, Toray, Zentalis. J. Lichfield: Financial Interests, Personal, Full or part-time Employment: MSD, UK; Financial Interests, Personal, Stocks or ownership: Merck & Co., Inc., Rahway, NJ, USA. W. Wang: Financial Interests, Personal, Full or part-time Employment: MSD, China; Financial Interests, Personal, Stocks or ownership: Merck & Co., Inc., Rahway, NJ, USA. R.J. Orlowski: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. A. Lortholary: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Clovis Oncology, Tesaro/GSK, Roche, MSD, Novartis. B.M. Slomovitz: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, GSK, Genentech, Merck, Immunogen, Novocure, Aadi, Seagen, Incyte; Non-Financial Interests, Member of Board of Directors: GOG Foundation. All other authors have declared no conflicts of interest.