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.
Part A(Safety Run-in Phase) - Pembrolizumab+ paclitaxel+ carboplatin followed by pembrolizumab combination with nesuparib Part B(Randomization Phase) \- Pembrolizumab+ p aclitaxel+ Carboplatin followed by Pembrolizumab combination with Nesuparib vs Pembrolizumab+ Paclitaxel+ Carboplatin followed by Pembrolizumab monotherapy
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
92
Nesuparib 150mg or 100mg, QD, PO
Pembrolizumab 400mg, IV, Q6W
National Cancer Center
Kyeonggi-do, South Korea
RECRUITINGSeverance hospital
Seoul, South Korea
RECRUITINGKorea University Guro Hospital
Seoul, South Korea
RECRUITINGSamsung Medical Center
Seoul, South Korea
RECRUITINGSeoul Asan Medical Center
Seoul, South Korea
RECRUITINGSeoul National University Hospital
Seoul, South Korea
RECRUITINGDose-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.
Time frame: 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.
Time frame: Approximately 11.01 months
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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: All 36 subjects in each groups are enrolled and the 18-month follow-up period ends
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