740MO - Dostarlimab + chemotherapy for the treatment of primary advanced or recurrent endometrial cancer (pA/rEC): Analysis of progression free survival (PFS) and overall survival (OS) outcomes by molecular classification in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial

Background

In the phase 3 RUBY trial (NCT03981796) dostarlimab (D) + carboplatin-paclitaxel (CP) significantly improved PFS vs CP alone in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H; HR, 0.28) and overall population (HR, 0.64) with a favorable OS trend (HR, 0.64). Four molecular EC subgroups were identified for prognostic and potential predictive value. Validated surrogate methods more readily available include POLε mutation (mut), dMMR, TP53 abnormal, and no specific molecular profile (NSMP). Here, we present exploratory efficacy outcomes by molecular classification.

Methods

Patients (pts) with pA/rEC were randomised 1:1 to receive dostarlimab, or placebo (PBO), plus CP, followed by dostarlimab or PBO monotherapy for up to 3 years. POLε and TP53 status were determined by DNAseq; MMR/MSI status was determined by testing used for study enrollment (immunohistochemistry, polymerase chain reaction, or next generation sequencing). Order of classification was POLεmut → dMMR/MSI-H → TP53mut → NSMP. PFS and OS were assessed for each subgroup.

Results

Of 494 pts enrolled and randomised, mutational data were available for 400 pts (81.0%), classified as: 5 (1.3%) POLεmut, 91 (22.8%) dMMR/MSI-H, 88 (22.0%) TP53mut, and 216 (54.0%) NSMP. PFS and OS results favored the D+CP arm in the dMMR/MSI-H, TP53mut, and NSMP subgroups, with the largest benefit observed in the dMMR and TP53mut groups. No pts with POLεmut progressed in either arm as of data cut (Table). Safety was reported previously.

Conclusions

Dostarlimab+CP is associated with improved PFS and OS in the dMMR/MSI-H, NSMP, and TP53 subgroups and adds prognostic value in pA/rEC. Patients with POLεmut had the best prognosis, as expected. Further research may help to validate these exploratory findings.

Table: 740MO

^aNo PFS or OS events were observed for patients classified as POLεmut in either arm INV, investigator assessment; NA, not applicable

Clinical trial identification

NCT01847274.

Editorial acknowledgement

Writing and editorial support, funded and coordinated by GSK, was provided by Shannon Morgan-Pelosi, PhD, and Mary C. Wiggin, of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

GSK.

Funding

GSK.

Disclosure

M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Karyopharm, Merck, Roche, Zailab; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK; Financial Interests, Personal, Member of Board of Directors: Karyopharm; Financial Interests, Personal, Stocks/Shares: Karyopharm; Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, Ultimovacs, Apexigen; Financial Interests, Institutional, Trial Chair: Deciphera; Non-Financial Interests, Advisory Role: Ultimovacs, Apexigen. M.S. Shahin: Financial Interests, Institutional, Funding: AstraZeneca, GSK, Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, GSK, Merck, Seagen; Financial Interests, Personal, Expert Testimony: Robindon & Havens PSC, Lexington KY; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Member of Board of Directors: Unite for Her. D. Cibula: Financial Interests, Personal, Advisory Board: Akesobio, AstraZeneca, GSK, MSD, Novocure, Roche, Seagen, SOTIO. F. Raspagliesi: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, GSK; Financial Interests, Personal, Other, Travel support: GSK; Financial Interests, Personal, Advisory Board: PharmaMar. L.C. Hanker: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, AstraZeneca, Clovis, Eisai, GSK, Intuitive Surgery, Janssen, MSD, Novartis, Pfizer, PharmaMar, Roche, Tesaro. R.L. Coleman: Financial Interests, Personal, Funding: AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, Roche/Genentech; Financial Interests, Personal, Speaker, Consultant, Advisor: AbbVie, Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genmab, GSK, Immunogen, Novocure, Merck, Roche/Genentech; Financial Interests, Personal, Advisory Board: Eisai/BMS, VBL Therapeutics. I.A. Boere: Financial Interests, Institutional, Funding: GSK; Financial Interests, Institutional, Advisory Board: AstraZeneca, GSK. L. Gilbert: Financial Interests, Institutional, Funding: Alkermes, AstraZeneca, Clovis, Esperas, IMV, Immunogen, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, Tesaro; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Alkermes, AstraZeneca, Eisai, Eisai-Merck, GSK. B.M. Slomovitz: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis, Eisai, GSK, Genentech, Merck, Immunogen, Novocure; Financial Interests, Personal, Other, consultant: GOG Foundation; Non-Financial Interests, Member of Board of Directors: GOG Foundation. M.A. Powell: Financial Interests, Personal, Speaker, Consultant, Advisor: GSK, Tesaro, Merck, Eisai, Seagen, Clovis Oncology, AstraZeneca. S. Ghosh, S. Stevens: Financial Interests, Personal, Full or part-time Employment: GSK. A. Stuckey: Financial Interests, Personal, Royalties: UptoDate. All other authors have declared no conflicts of interest.