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

NCT06502743 | Recruiting Phase 2

• 1 other identifier: 4-2024-0577
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Endometrial Cancer; Recurrent Endometrial Carcinoma; Endometrial Carcinoma; Gynecologycal Cancer; Endometrial Neoplasms

Keywords

Nesuparib; pMMR; MMR-proficient

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• 3, 6, 9 12-month Progression-free rate(PFS rate)

  3month, 6month, 9month, 12month after the study enrollment

• Median Progression-free time(Median PFS time)

  All 36 subjects in each groups are enrolled and the 18-month follow-up period ends

• Overall response rate(ORR)

  All 36 subjects in each groups are enrolled and the 18-month follow-up period ends

• Duration control rate(DCR)

  All 36 subjects in each groups are enrolled and the 18-month follow-up period ends

• Duration of response(DOR)

  All 36 subjects in each groups are enrolled and the 18-month follow-up period ends

Study Arms (3)

Part B - Pembrolizumab monotherapy

EXPERIMENTAL

Chemotherapy Treatment Pembrolizumab 200 mg IV Day 1 + Paclitaxel 175mg/m2 IV over 3 hours Day 1 + Carboplatin AUC 5 IV Day 1 x 6 cycles (one cycle = 3 weeks Maintenance Treatment Pembrolizumab 400 mg IV Day 1 x up to 14 cycles (o ne cycle = 6 weeks ) Maximum number of Pembrolizumab cycles (Chemotherapy Treatment + maintenance Treatment ) = 20

Drug: Pembrolizumab

Part B - Pembrolizumab and nesuparib combination therapy

EXPERIMENTAL

Combination therapy Chemotherapy Treatment Pembrolizumab 200 mg IV Day 1 + Paclitaxel 175mg/m2 IV over 3 hours Day + Carboplatin AUC 5 IV Day 1 x 6 cycles (one cycle = 3 weeks) Maintenance Treatment Pembrolizumab 400 mg IV Day 1 + Nesuparib 150mg or 100mg QD PO x up to 14 cycles (o ne cycle = 6 weeks ) Maximum number of Pembrolizumab cycles (Chemotherapy Treatment + maintenance Treatment ) = 20

Drug: Nesuparib; Drug: Pembrolizumab

Part A - Safety Run-in Phase

EXPERIMENTAL

Chemotherapy Treatment: Pembrolizumab 200 mg IV Day 1 + Paclitaxel 175mg/m2 IV over 3 hours Day 1 + Carboplatin AUC 5 IV Day 1 x 6 cycles (one cycle = 3 weeks) Maintenance Treatment: Pembrolizumab 400 mg IV Day 1 + Nesuparib 150mg or 100mg QD PO x up to 14 cycles (one cycle = 6 weeks) Maximum number of Pembrolizumab cycles (Chemotherapy Treatment + Maintenance Treatment) = 20

Drug: Nesuparib; Drug: Pembrolizumab

Interventions

Nesuparib DRUG

Nesuparib 150mg or 100mg, QD, PO

Part A - Safety Run-in Phase; Part B - Pembrolizumab and nesuparib combination therapy

Pembrolizumab DRUG

Pembrolizumab 400mg, IV, Q6W

Part A - Safety Run-in Phase; Part B - Pembrolizumab and nesuparib combination therapy; Part B - Pembrolizumab monotherapy

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 must provide the institutional (local) P53 IHC result.
• Prior Therapy;
• Naïve to first line systemic anti-cancer treatment. For patients with recurrent disease only, prior systemic anti-cancer treatment is allowed only if provided adjuvant chemotherapy was completed ≥ 12 months prior to randomization.
• a. Note : For Part A(Safety lead in phase), patient who used Paclitaxel, Carboplatin and Pembrolizumab for first line systemic therapy can participate if they meet all of the following conditions. Patient must have had 6 cycles of chemotherapy; patient must have physician assessed stable disease (SD), partial response (PR), or complete response (CR) after 6 cycles of therapy and patient must be enrolled within 9 weeks of their last dose of chemotherapy (last dose is the day of the last infusion)
• Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy. All radiation therapy must be completed at least 4 weeks prior to randomization.
• Patients may have received prior hormonal therapy for treatment of endometrial cancer. All hormonal therapy must be discontinued at least three weeks prior to randomization.
• Archival tumor tissue available or a fresh biopsy must be obtained prior to randomization.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Have adequate organ function. Specimens must be collected within 7days prior to the start of study intervention.
• \- Hematology Absolute neutrophil count (ANC) ≥1,500/μL without growth factor support within 2 weeks before screening test.
• Platelet ≥100,000/μL without transfusion within 2 weeks prior to screening test.

You may not qualify if:

• 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.
• Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with treated brain metastases may be eligible if follow-up brain imaging after CNS directed therapy shows no evidence of progression, and they have been off steroids for at least 4 weeks prior to randomization and remain clinically stable.
• Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
• Patient has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization.
• Patients who have received steroids as CT scan contrast premedication may be enrolled.
• The use of inhaled or topical corticosteroids is allowed.
• The use of mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
• The use of physiologic doses of corticosteroids may be approved after consultation with the study chair.
• Patients who have a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
• Patient with uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (except for uncomplicated urinary tract infection), interstitial lung disease or active, noninfectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patient has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

Sponsors & Collaborators

• Yonsei University: lead
• Onconic Therapeutics Inc.: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (6)

National Cancer Center

Kyeonggi-do, South Korea

RECRUITING

Severance hospital

Seoul, 03722, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, South Korea

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

Seoul Asan Medical Center

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Related Publications (1)

• Kim SI, Cho HW, Choi CH, Park JY, Lee JB, Kim JW, Kim BG, Kim J, Lee JY. 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). J Gynecol Oncol. 2025 Dec 22. doi: 10.3802/jgo.2026.37.e50. Online ahead of print.

  PMID: 41514313 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

JUNGYUN LEE, Ph.D

CONTACT

82)2-2228-2237; JUNGYUNLEE@yuhs.ac

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 23, 2024
• First Posted: July 16, 2024
• Study Start: September 12, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 3, 2025

Record last verified: 2025-03

Locations

KR (6)