First-line Carboplatin and Paclitaxel in Combination With Pembrolizumab, Followed by Maintenance Pembrolizumab With or Without Nesuparib, in Patients With Newly Diagnosed Advanced or Recurrent MMR-proficient (pMMR) Endometrial Cancer
NCT Number: NCT06502743
Acronym: PENELOPE
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Endometrial Cancer|Recurrent Endometrial Carcinoma|Endometrial Carcinoma|Gynecologycal Cancer|Endometrial Neoplasms
Interventions: DRUG: Nesuparib|DRUG: Pembrolizumab
Sponsor: Yonsei University
Collaborators: Onconic Therapeutics Inc.|Merck Sharp & Dohme LLC
Sex: FEMALE
Age: ADULT, OLDER_ADULT
Enrollment: 92
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2027-12

Summary:
The goal of this study is listed below.

Part A (Safety Run-in Phase) : To determine feasibility of pembrolizumab and nesuparib combination as maintenance therapy in patients with MMR-proficient advanced and recurrent endometrial cancer. Feasibility is defined as a dose-limiting toxicity (DLT) rate less than or equal to 33%.

Part B (Randomization Phase)

: To evaluate the efficacy of pembrolizumab and nesuparib combination/ pembrolizumab monotherapy as maintenance therapy in patients with MMR-proficient advanced stage and recurrent endometrial cancer. Efficacy will be assessed by investigator assessed progression free survival (PFS) as assessed by RECIST 1.1.

Primary Outcome Measures: Dose-limiting toxicities, In Part A, To evaluate dose-limiting toxicities(DLTs) of combination maintenance treatment with pembrolizumab and nesuparib during the 21 days from first nesuparib and pembrolizumab administration, and to establish a recommended Phase 2 dose(RP2D) and dosing schedule., Assessed during 21days from day 1 of first combination maintenance treatment cycle (i.e., 21 days of Cycle 8 from day 1)|Overall distribution of progression-free survival, The time from randomization to the time when Progressive disease(PD) is first confirmed after administration of the first investigational drug (Pembrolizumab) or until death without disease progression., Approximately 11.01 months
Secondary Outcome Measures: 3, 6, 9 12-month Progression-free rate(PFS rate), the proportion of patients who are alive and without disease progression after administering the investigational product, 3month, 6month, 9month, 12month after the study enrollment|Median Progression-free time(Median PFS time), the proportion of patients who are alive and without disease progression after administering the investigational product, All 36 subjects in each groups are enrolled and the 18-month follow-up period ends|Overall response rate(ORR), the proportion of patients achieving complete remission(CR) or partial response(PR) as assessed by the Investigator per RECIST(v1.1) in patients who enter the study with measurable disease., All 36 subjects in each groups are enrolled and the 18-month follow-up period ends|Duration control rate(DCR), the proportion of subjects who have achieved a best overall response of complete remission(CR), partial response(PR), or stable disesae(SD) per RECIST v.1.1 based on Investigator assessment., All 36 subjects in each groups are enrolled and the 18-month follow-up period ends|Duration of response(DOR), DOR applies only to subjects whose BOR was CR or PR in patients who enter the study with measurable disease according to RECIST v.1.1 using the Investigator's tumor assessment. The start date is the date of first documented response (CR or PR), and the end date is the date defined as first documented PD or death due to any cause. If a subject had not had an event, duration will be censored at the date of last adequate tumor assessment., All 36 subjects in each groups are enrolled and the 18-month follow-up period ends|Overall survival(OS), the time from the first date of investigational product administration to the date of death for any reason., All 36 subjects in each groups are enrolled and the 18-month follow-up period ends|Progression free survival 2(PFS2), the time from the first date of administration of the investigational product to the earlier of disease progression or death in the subsequent anticancer therapy., All 36 subjects in each groups are enrolled and the 18-month follow-up period ends