KEYNOTE-C93/GOG-3064/ENGOT-en15: A phase 3, randomized, open-label study of first-line pembrolizumab versus platinum-doublet chemotherapy in mismatch repair deficient advanced or recurrent endometrial carcinoma.

• DOI: 10.1200/jco.2022.40.16_suppl.tps5623
• Publication Date: 2022-06-06T16:32:40Z
• Authors: Brian M. Slomovitz; David Cibula; Tayup Simsek; Mansoor Raza Mirza; Beata Maćkowiak-M...; Emma Hudson; Ignacio Romero; Nicoletta Colombo; Jacob Korach; Rutie Yin; Lucy Gilbert; Kosei Hasegawa; Alexandra Tyulyan...; Sally E. Baron-Hay; Lyndsay Willmott; Floor Jenniskens ...; Robert J. Orlowski; Xuan Zhou; Vivek Khemka; Sandro Pignata
• Keywords: Carboplatin

TPS5623 Background: Carboplatin-paclitaxel chemotherapy (with trastuzumab for HER2+ uterine serous carcinoma) is the standard of care first-line systemic treatment recurrent or metastatic endometrial carcinoma (EC), which has a 5-year relative survival rate only 17%. Worse outcomes have been shown mismatch repair deficient (dMMR) subtype EC. Pembrolizumab (pembro), an anti-PD-1 antibody, showed compelling antitumor activity in previously treated, advanced MSI-H/dMMR EC phase 2 KEYNOTE-158 study (ORR, 48%; median duration response [DOR], not reached; O’Malley JCO 2022). KEYNOTE-C93/GOG-3064/ENGOT-en15 (NCT05173987) 3, randomized, open-label evaluating pembro versus carboplatin-paclitaxel patients with dMMR Methods: Patients aged ≥18 years histologically confirmed stage III/IV including carcinosarcoma (mixed Mullerian tumor), radiographically evaluable disease (measurable nonmeasurable per RECIST v1.1), no prior therapy (prior radiation without radiosensitizing > weeks before first dose hormonal ≥1 week randomization permitted), and ECOG PS ≤1 are eligible. must central confirmation status. Approximately 350 will be randomized 1:1 to receive 400 mg IV Q6W 18 cycles (̃2 years) carboplatin AUC 5 6 mg/mL/min Q3W paclitaxel 175 mg/m option cycles). Trastuzumab permitted arm Randomization stratified by status (newly diagnosed vs EC) histology (endometrioid nonendometrioid). Treatment continue specified number until PD unacceptable toxicity. following blinded independent review (BICR). Tumor imaging performed Q9W from 54 Q12W thereafter. AEs assessed 30 days (90 serious AEs) after discontinuation graded NCI CTCAE version 5.0. Dual primary endpoints PFS v1.1 BICR OS. Secondary ORR, control rate, DOR BICR; investigator review; PFS2 (ie, time assessment death any cause start subsequent anticancer therapy); safety; patient-reported outcomes. OS estimated Kaplan-Meier method, differences log-rank test HRs 95% CIs determined using Cox proportional hazard model. Enrollment ongoing. Clinical trial information: NCT05173987.