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.
Patient must be female ≥ 19 years of age
Histologic confirmation of the original primary tumor is required. Patients with the following histologic types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, carcinosarcoma, adenocarcinoma not otherwise specified (N.O.S.).
Measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial cancer.
MMR proficient confirmed by institutional (local) MMR IHC testing.
Patient has undergone prior treatment with a known PARP inhibitor.
Patient has a known hypersensitivity to nesuparib, pembrolizumab or combination cytotoxic chemotherapy components or excipients.
MMR deficiency confirmed by institutional MMR IHC testing.
Patients who are currently participating and receiving cancer-directed study therapy or have participated in a study of an investigational agent and received cancer-directed study therapy within 4 weeks prior to randomization.
Parallel
Nesuparib
DrugNesuparib 150mg or 100mg, QD, PO
Pembrolizumab
DrugPembrolizumab 400mg, IV, Q6W
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.
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.
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
Median Progression-free time(Median PFS time)
the proportion of patients who are alive and without disease progression after administering the investigational product
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.
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.
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Yonsei University
Lead sponsor
Onconic Therapeutics Inc.
Collaborator
Merck Sharp & Dohme LLC
Collaborator
