748P - Outcomes for patients (pts) with advanced endometrial cancer (aEC) who completed pembrolizumab (pembro) and continued lenvatinib (LEN) in the phase III Study 309/KEYNOTE-775

Background

The primary analysis of Study 309/Keynote-775 demonstrated clinically and statistically significant progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) improvements in pts with aEC randomized to LEN + pembro vs chemotherapy (all-comers and pts with mismatch repair-proficient [pMMR] tumors). Pts received pembro for up to 2 yrs and continued LEN until progression or toxicity. This exploratory analysis reports outcomes in pts who completed 2 yrs of pembro and continued LEN at the final prespecified OS analysis (cutoff: 1 Mar 22).

Methods

Pts with aEC and 1 prior platinum-based chemotherapy (up to 2 if 1 given in [neo]adjuvant setting) were randomized to LEN 20 mg PO QD + pembro 200 mg IV Q3W (up to 35 cycles) or chemotherapy (doxorubicin 60 mg/m² IV Q3W or paclitaxel 80 mg/m² IV QW [3 wks on; 1 wk off]), and stratified by MMR status (pMMR pts were further stratified by ECOG PS, geographic region, and pelvic irradiation history). We report PFS, OS, ORR, duration of response (DOR), and safety in all-comer and pMMR pts who completed 35 cycles (≈2 yrs) of pembro and continued LEN.

Results

Of 411 pts randomized to LEN + pembro (pMMR n=346), 41 (pMMR n=30) completed 35 pembro cycles, continued LEN, and are included in the analysis. Median PFS (95% CI) was 34.1 mos (20.1-not evaluable [NE]) in pMMR pts and 34.1 mos (27.7-NE) in all-comers. Median OS (95% CI) was not reached (NR [NE]) in pMMR pts and all-comers. ORR (95% CI) was 63.3% (43.9-80.1) in pMMR pts and 63.4% (46.9-77.9) in all-comers; 7 pMMR pts and 8 all-comers had a complete response. Median DOR was NR (range, 3.5-39.5+) in pMMR pts and all-comers. Grade ≥3 treatment-related adverse events occurred in 80.5% of all-comers (Table).

Table: 748P

^aBlinded Independent Central Review, RECIST v1.1 ^bProduct-limit (Kaplan-Meier) method for censored date. ^cReported in all-comers only. AE, adverse event; CR, complete response.

Conclusions

Ongoing clinical benefit in pembro completers who continued LEN supports LEN + pembro as standard of care in pts with aEC who received prior platinum therapy.

Clinical trial identification

NCT03517449.

Editorial acknowledgement

Medical writing support was provided by Irene Minkina, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA.

Legal entity responsible for the study

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

Funding

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

Disclosure

E. Colomba: Financial Interests, Personal, Invited Speaker: Eisai, BMS, GSK; Financial Interests, Personal, Advisory Board: Pfizer, BMS, Eisai, MSD, GSK; Financial Interests, Institutional, Principal Investigator: BeiGene, MSD. 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 insitutional 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. H. Mackay: Financial Interests, Personal, Advisory Board: Eisai, GAK; Financial Interests, Personal, Other, Associate Editor: British Journal of Cancer. R. Moore: Financial Interests, Personal, Invited Speaker: Fujirebio Diagnostics Inc; Financial Interests, Personal, Advisory Board: Advisory Board X Fujirebio Diagnostics Inc. X ; Financial Interests, Institutional, Research Grant: Angle plx. K. Yonemori: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Sanofi, Genmab, Gilead, OncoXerna, Takeda, Novartis, MSD; Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR Pharma, MSD, Ono, BMS, Boehringer lngelheim, Daiichi Sankyo, Bayer, Jansen, Sanofi; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seagen, Eisai, Eli Lilly, Genmab, Boeringer Ingelheim, Kyowa Hakko Kirrin, Nihon Kayaku, Haihe. R. Xie: Financial Interests, Personal, Full or part-time Employment: Eisai. G. Barresi: Financial Interests, Personal, Full or part-time Employment: Merck Sharp and Dohme; Financial Interests, Personal, Stocks/Shares: Merck Sharp and Dohme; Financial Interests, Personal, Sponsor/Funding: Merck Sharp & Dohme. J. McKenzie: Financial Interests, Personal, Full or part-time Employment: Eisai. V. Makker: Financial Interests, Institutional, Funding, Study funding: Merck, Eisai, Clovis, Karyopharm, AstraZeneca; Financial Interests, Institutional, Funding, Study support: Zymeworks; Financial Interests, Institutional, Funding, Study Support: BMS, Duality, Faeth, Takeda; Non-Financial Interests, Principal Investigator: Merck; Non-Financial Interests, Advisory Role: Eisai, Clovis, Novartis, Lilly, GSK, Karyopharm, Iteos, Faeth, Duality, ZYmeworks, Morphosys, Moreo. All other authors have declared no conflicts of interest.