726MO - Outcomes by histology and prior therapy with lenvatinib plus pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer (Study 309/KEYNOTE-775)

Background

Study 309/KEYNOTE-775 (NCT03517449) is a phase III trial comparing efficacy and safety of lenvatinib (LEN) + pembrolizumab (pembro) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated, advanced endometrial cancer (EC). LEN + pembro significantly improved OS and PFS vs TPC in the ITT population (all comers) (HR [95% CI]: OS 0.62 [0.51−0.75]; PFS 0.56 [0.47−0.66]) and in pts with mismatch repair-proficient (pMMR) status (HR [95% CI]: OS 0.68 [0.56−0.84]; PFS 0.60 [0.50−0.72]). We present efficacy outcomes in pts grouped by tumor histology and prior therapy (tx).

Methods

Eligible pts were ≥18 y with histologically confirmed, previously treated, advanced EC, and a tumor sample for determining MMR status. Pts were randomized to LEN 20 mg PO QD + pembro 200 mg IV Q3W (max. 35 cycles) or TPC (doxorubicin 60 mg/m² Q3W [max. cumulative dose, 500 mg/m²] or paclitaxel 80 mg/m² QW, 3 wks on, 1 wk off). Randomization was stratified by MMR status (proficient vs deficient), then pMMR pts were stratified by ECOG PS (0 vs 1), geographic region, and prior pelvic radiation. Treatment continued until PD, toxicity, or pt withdrawal. Primary endpoints were OS and PFS (RECIST v1.1 by BICR).

Results

827 pts were enrolled (LEN + pembro, n=411; TPC, n=416). Median (range) time from randomization to data cutoff (Oct 26, 2020) was 16.8 (8.7−28.0) mo. HRs for OS favored LEN + pembro over TPC in most subgroups defined by tumor histology and prior tx (Table). PFS outcomes were consistent with those for OS (to be presented).

Conclusions

LEN + pembro provided meaningful efficacy improvements in pts with previously treated advanced EC across all histologies (including difficult to treat histologies), and irrespective of prior (neo)adjuvant tx, and platinum-free interval (PFI) from most recent platinum tx. Pts with 1 prior line of platinum had greater benefit than those with ≥1 line, supporting early use of LEN + pembro. Table: 726MO

Clinical trial identification

NCT03517449.

Editorial acknowledgement

Medical writing assistance was provided by Kathleen Estes, PhD, of ICON plc (North Wales, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

N. Colombo: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pharmamar; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD/Merk; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: BIOCAD; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Oncxerna; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Pharmamar; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: MSD/Merk; Financial Interests, Personal, Other, Honoraria: Clovis Oncology; Financial Interests, Personal, Other, Honoraria: Tesaro; Financial Interests, Personal, Other, Honoraria: GSK; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Other, Honoraria: BIOCAD; Financial Interests, Personal, Other, Honoraria: Immunogen; Financial Interests, Personal, Other, Honoraria: Mersana; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Oncxerna; Financial Interests, Personal, Other, Travel Expenses: Roche; Financial Interests, Personal, Other, Travel Expenses: Pharmamar; Financial Interests, Personal, Other, Travel Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel Expenses: MSD/Merk; Financial Interests, Personal, Other, Travel Expenses: Clovis Oncology; Financial Interests, Personal, Other, Travel Expenses: Tesaro; Financial Interests, Personal, Other, Travel Expenses: GSK; Financial Interests, Personal, Other, Travel Expenses: Novartis; Financial Interests, Personal, Other, Travel Expenses: Pfizer; Financial Interests, Personal, Other, Travel Expenses: Takeda; Financial Interests, Personal, Other, Travel Expenses: BIOCAD; Financial Interests, Personal, Other, Travel Expenses: Immunogen; Financial Interests, Personal, Other, Travel Expenses: Mersana; Financial Interests, Personal, Other, Travel Expenses: Eisai; Financial Interests, Personal, Other, Travel Expenses: Oncxerna. D. Lorusso: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Tesaro/GSK; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pharmamar; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: Genmab; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: Tesaro/GSK; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Pharmamar; Financial Interests, Institutional, Research Grant: Clovis; Financial Interests, Personal, Expert Testimony: Clovis; Financial Interests, Personal, Other, PI of Registrative Trials: Roche; Financial Interests, Personal, Other, PI of Registrative Trials: Pharmamar; Financial Interests, Personal, Other, PI of Registrative Trials: Tesaro; Financial Interests, Personal, Other, PI of Registrative Trials: Clovis; Financial Interests, Personal, Other, PI of Registrative Trials: Immunogen; Financial Interests, Personal, Other, PI of Registrative Trials: Genmab; Financial Interests, Personal, Other, PI of Registrative Trials: AstraZeneca; Financial Interests, Personal, Other, PI of Registrative Trials: Merck; Financial Interests, Personal, Other, Travel Support and hospital meeting: Roche; Financial Interests, Personal, Other, Travel Support and hospital meeting: Pharmamar; Financial Interests, Personal, Other, Travel Support and hospital meeting: AstraZeneca; Financial Interests, Personal, Other, Travel Support and hospital meeting: Tesaro/GSK; Financial Interests, Personal, Other, Travel Support and hospital meeting: Amgen; Non-Financial Interests, Personal, Member of the Board of Directors: ENGOT; Non-Financial Interests, Personal, Member of the Board of Directors: AIOM; Non-Financial Interests, Personal, Member of the Board of Directors: MITO; Non-Financial Interests, Personal, Member of the Board of Directors: ESGO; Non-Financial Interests, Personal, Member of the Board of Directors: ESMO. A. Casado Herráez: Financial Interests, Personal, Advisory Board: Roche, Pharmamar, Lilly, Eisai/Merck; Financial Interests, Institutional, Research Grant: Roche, Lilly, Pharmamar, Eisai, Astra/Zeneca, Tesaro/GSK; Financial Interests, Personal, Other, Travel support for attendance to major international oncological conferences (ASCO, ESMO, SGO, CTOS, ESGO): Pharmamar, Roche, AstraZeneca, Merck; Non-Financial Interests, Personal, Other, Member: EORTC GCG, EORTC STBSG, GCIG, ENGOT and Spanish Society of Medical Oncology (SEOM). A.D. Santin: Financial Interests, Personal, Research Grant: Puma; Financial Interests, Personal, Research Grant: Immunomedics; Financial Interests, Personal, Research Grant: Gilead; Financial Interests, Personal, Research Grant: Synthon; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Other, Personal Fees: Merck; Financial Interests, Personal, Research Grant: Boehinger-Ingelheim; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: Tesaro; Financial Interests, Personal, Other, Personal Fees: Tesaro; Financial Interests, Personal, Research Grant: Eisai; Financial Interests, Personal, Other, Personal Fees: Eisai. E. Colomba: Financial Interests, Personal and Institutional, Other, Honoraria: BMS; Financial Interests, Personal and Institutional, Other, Honoraria: Clovis; Financial Interests, Personal and Institutional, Other, Honoraria: Ispen; Financial Interests, Personal and Institutional, Other, Honoraria: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Merck; Financial Interests, Personal and Institutional, Advisory Role: MSD; Financial Interests, Personal and Institutional, Advisory Role: BMS; Financial Interests, Personal and Institutional, Advisory Role: Ispen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: BMS; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Ispen. D.S. Miller: Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Karyopharm; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Advisory Board: Tarveda; Financial Interests, Personal, Advisory Board: Myriad; Financial Interests, Personal, Advisory Board: GalxoSmithKline; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Member of the Board of Directors: NRG Oncology; Financial Interests, Personal, Research Grant: NRG Oncology; Financial Interests, Personal, Research Grant: Karyopharm; Financial Interests, Personal, Research Grant: Advaxis; Financial Interests, Personal, Research Grant: Immunogen; Financial Interests, Personal, Research Grant: Advenchent; Financial Interests, Personal, Research Grant: Regeneron; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Agenus; Financial Interests, Personal, Research Grant: Akesobio; Financial Interests, Personal, Research Grant: EMD Serono; Financial Interests, Personal, Leadership Role: NRG Oncology. K. Fujiwara: Financial Interests, Personal, Advisory Board: MSD, Eiisai, Genmab; Financial Interests, Institutional, Research Grant: MSD, Eisai, AstraZenca, Chugai-Roche, Clovis, Regenerone; Non-Financial Interests, Personal, Member of the Board of Directors: GCIG (Immediate Past Chair), IGCS (President Elect), GOTIC (Vice Chair), NRG Oncology (PI for Japan). S. Pignata: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Clovis; Financial Interests, Personal, Other, Honoraria: Pharmamar. A. Floquet: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Pharma Mar; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Clovis Oncology; Financial Interests, Personal, Other, Honoraria: GSK; Financial Interests, Personal, Other, Honoraria: Pharma Mar; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: MSD; Financial Interests, Personal, Other, Travel expenses: Clovis Oncology; Financial Interests, Personal, Other, Travel expenses: GSK; Financial Interests, Personal, Other, Travel expenses: Pharma Mar. B.J. Monk: Financial Interests, Personal, Other, Honorarium: Agenus, Akeso Bio, Iovance, Puma, AstraZeneca, Eisai, Elevar, Genmab/Seattle Genetics, GOG Foundation, Merck, McKesson, Tesaro/GSK, Aravive, Gradalis, ImmunoGen, Mersana, Novocure, Myriad, Pfizer, Roche/Genentech, VBL, Karyopharm, Clovis, Sorrento. S. Banerjee: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Clovis, GSK, Immunogen, Mersana, Merck Serono, MSD, Pfizer, Roche, Oncoxerna; Financial Interests, Institutional, Research Grant: AstraZeneca, Tesaro, GSK. R.T. Penson: Financial Interests, Personal, Funding: Array BioPharma Inc., AstraZeneca, Genentech, Vascular Biogenics Ltd.; Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, Clovis Oncology, Curio Science, Eisai Inc., Genentech, Janssen Oncology (J&J), Merck & Co., Mersana Therapeutics, Inc., NewLink Genetics, Nexus Global Group, Pieris Pharma Inc, Roche, Inc., Sutro Biopharma, Syndax Pharmaceuticals, Tes; Non-Financial Interests, Personal, Advisory Board: Care4ward. R. Kristeleit: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: InCyte; Financial Interests, Personal, Advisory Board: Pharmamar; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Honoraria: GSK; Financial Interests, Personal, Other, Honoraria: Clovis; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: InCyte; Financial Interests, Personal, Other, Honoraria: Pharmamar; Financial Interests, Personal, Other, Honoraria: Roche. M. Fabbro: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK. M. Orlando: Financial Interests, Personal, Advisory Board: Eli Lilly, Amgen. H. Mackay: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK. E. Jensen: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. L. Dutta: Financial Interests, Personal, Full or part-time Employment: Eisai Inc., Woodcliff, NJ, USA. R. Orlowski: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. V. Makker: Financial Interests, Personal, Advisory Board: ArQule; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Karyopharm; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: IBM Watson; Financial Interests, Personal, Advisory Board: Moreo; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Advisory Board: Faeth; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Honoraria: ArQule; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Karyopharm; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Clovis; Financial Interests, Personal, Other, Honoraria: IBM Watson; Financial Interests, Personal, Other, Honoraria: Moreo; Financial Interests, Personal, Other, Honoraria: Deciphera; Financial Interests, Personal, Other, Honoraria: Faeth; Financial Interests, Personal, Other, Honoraria: GSK; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Travel Expenses: ArQule; Financial Interests, Personal, Other, Travel Expenses: Eisai; Financial Interests, Personal, Other, Travel Expenses: Karyopharm; Financial Interests, Personal, Other, Travel Expenses: Merck; Financial Interests, Personal, Other, Travel Expenses: Clovis; Financial Interests, Personal, Other, Travel Expenses: IBM Watson; Financial Interests, Personal, Other, Travel Expenses: Moreo; Financial Interests, Personal, Other, Travel Expenses: Deciphera; Financial Interests, Personal, Other, Travel Expenses: Faeth; Financial Interests, Personal, Other, Travel Expenses: GSK; Financial Interests, Personal, Other, Travel Expenses: AstraZeneca; Financial Interests, Personal, Funding, Study Funding: AstraZeneca; Financial Interests, Personal, Funding, Study Funding: Eisai; Financial Interests, Personal, Funding, Study Funding: Karyopharm; Financial Interests, Personal, Funding, Study Funding: Lilly; Financial Interests, Personal, Funding, Study Funding: Merck; Financial Interests, Personal, Funding, Study Funding: Takeda; Financial Interests, Personal, Funding, Study Funding: Genentech; Financial Interests, Personal, Funding, Study Funding: Zymeworks; Financial Interests, Personal, Funding, Study Funding: Moreo.