Phase II randomized study of first-line carboplatin and paclitaxel in combination with pembrolizumab, followed by maintenance pembrolizumab alone or with nesuparib, in mismatch-repair proficient, advanced or recurrent endometrial cancer (PENELOPE).
[BACKGROUND] Although recent clinical trials proved survival benefit from the addition of immune checkpoint inhibitors to standard chemotherapy, treatment of mismatch repair-proficient (pMMR) advanced
APA
Kim SI, Cho HW, et al. (2026). Phase II randomized study of first-line carboplatin and paclitaxel in combination with pembrolizumab, followed by maintenance pembrolizumab alone or with nesuparib, in mismatch-repair proficient, advanced or recurrent endometrial cancer (PENELOPE).. Journal of gynecologic oncology, 37(1), e50. https://doi.org/10.3802/jgo.2026.37.e50
MLA
Kim SI, et al.. "Phase II randomized study of first-line carboplatin and paclitaxel in combination with pembrolizumab, followed by maintenance pembrolizumab alone or with nesuparib, in mismatch-repair proficient, advanced or recurrent endometrial cancer (PENELOPE).." Journal of gynecologic oncology, vol. 37, no. 1, 2026, pp. e50.
PMID
41514313
Abstract
[BACKGROUND] Although recent clinical trials proved survival benefit from the addition of immune checkpoint inhibitors to standard chemotherapy, treatment of mismatch repair-proficient (pMMR) advanced or recurrent endometrial cancer (arEC) is challenging. As poly(ADP-ribose) polymerase (PARP) inhibitors enhance the effects of immune checkpoint inhibitors when combined, improvement of survival is expected by dual maintenance in this population. The PENELOPE trial will investigate the efficacy and safety of dual maintenance with nesuparib, an orally active PARP1/2 and tankyrase 1/2 inhibitor, and pembrolizumab after paclitaxel/carboplatin plus pembrolizumab (TCP) treatment in patients with pMMR arEC.
[METHODS] In this multicenter, randomized, open-label, non-comparative phase II trial, patients with pMMR arEC, naïve to first-line chemotherapy, will be enrolled. Six patients will be enrolled in stage 1 (safety run-in) and treated with TCP for 6 cycles followed by dual maintenance with nesuparib and pembrolizumab. The study will proceed to stage 2 (dose expansion) if less than 33% of patients in stage 1 experience a dose-limiting toxicity. Otherwise, additional patients will be enrolled in stage 1 at a lower dose level. In stage 2, 80 patients will be randomized (1:1) to: arm A) TCP followed by maintenance with pembrolizumab; arm B) TCP followed by dual maintenance with nesuparib and pembrolizumab. Patients are planned to receive maintenance treatment up to 14 cycles every 6 weeks. Primary endpoint is investigator-assessed progression-free survival (Response Evaluation Criteria in Solid Tumors 1.1) of each arm vs. historical control, which is the placebo arm for pMMR patients in the NRG-GY018 study, and key secondary endpoints are overall survival, overall response rate, disease control rate, duration of response, and safety. Enrollment began in Q4 2024.
[TRIAL REGISTRATION] ClinicalTrials.gov Identifier: NCT06502743.
[METHODS] In this multicenter, randomized, open-label, non-comparative phase II trial, patients with pMMR arEC, naïve to first-line chemotherapy, will be enrolled. Six patients will be enrolled in stage 1 (safety run-in) and treated with TCP for 6 cycles followed by dual maintenance with nesuparib and pembrolizumab. The study will proceed to stage 2 (dose expansion) if less than 33% of patients in stage 1 experience a dose-limiting toxicity. Otherwise, additional patients will be enrolled in stage 1 at a lower dose level. In stage 2, 80 patients will be randomized (1:1) to: arm A) TCP followed by maintenance with pembrolizumab; arm B) TCP followed by dual maintenance with nesuparib and pembrolizumab. Patients are planned to receive maintenance treatment up to 14 cycles every 6 weeks. Primary endpoint is investigator-assessed progression-free survival (Response Evaluation Criteria in Solid Tumors 1.1) of each arm vs. historical control, which is the placebo arm for pMMR patients in the NRG-GY018 study, and key secondary endpoints are overall survival, overall response rate, disease control rate, duration of response, and safety. Enrollment began in Q4 2024.
[TRIAL REGISTRATION] ClinicalTrials.gov Identifier: NCT06502743.
MeSH Terms
Humans; Female; Endometrial Neoplasms; Antibodies, Monoclonal, Humanized; Paclitaxel; Carboplatin; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; DNA Mismatch Repair; Clinical Trials, Phase II as Topic; Middle Aged; Poly(ADP-ribose) Polymerase Inhibitors; Aged; Randomized Controlled Trials as Topic; Adult; Multicenter Studies as Topic