Phase 2 Study of First-line Carboplatin and Paclitaxel with Pembrolizumab, Followed by Maintenance Pembrolizumab With or Without Nesuparib, in Patients With Newly Diagnosed Advanced or Recurrent MMR-proficient Endometrial Cancer
Led by Yonsei University · Updated on 2025-04-03
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Yonsei University
Lead Sponsor
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Onconic Therapeutics Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating a combination of pembrolizumab and nesuparib as a maintenance therapy for female patients with MMR-proficient advanced and recurrent endometrial cancer. The study includes a safety run-in phase to assess whether the treatment is tolerable and a randomized phase to compare the effectiveness of pembrolizumab alone versus pembrolizumab with nesuparib. The main goal is to understand how these treatments affect progression-free survival.
Participants receive first-line chemotherapy with pembrolizumab, paclitaxel, and carboplatin for six cycles, followed by maintenance treatment. During maintenance, one group receives pembrolizumab alone, while another receives pembrolizumab combined with nesuparib taken orally daily. Pembrolizumab is given intravenously every six weeks, and the treatment period includes up to 14 maintenance cycles. The study has two parts: an initial safety phase and a randomized phase comparing the two maintenance treatments.
Throughout the study, participants will have regular assessments including monitoring for dose-limiting toxicities, tumor response evaluations, and survival outcomes. Blood tests and tumor tissue samples are collected to check organ function and molecular markers. Safety and treatment effects will be followed up for up to 18 months after enrollment. The total number of pembrolizumab cycles, including chemotherapy and maintenance, can be up to 20. Participants will be closely monitored for side effects and disease progression during the trial.
CONDITIONS
Brief Title
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
Who Can Participate
Age: 19Years +
FEMALE
Eligibility Criteria
You may qualify if you...
Patient must be female aged 19 years or older
Histologic confirmation of specified endometrial cancer types including endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, carcinosarcoma, or adenocarcinoma not otherwise specified
Measurable stage III, IVA, IVB, or recurrent endometrial cancer
MMR proficiency confirmed by local testing
Provide institutional P53 IHC result
Nafve to first-line systemic anti-cancer treatment or prior adjuvant chemotherapy completed at least 12 months before randomization for recurrent disease
Prior radiation therapy completed at least 4 weeks before randomization
Prior hormonal therapy discontinued at least 3 weeks before randomization
Archival tumor tissue available or fresh biopsy prior to randomization
ECOG performance status 0, 1, or 2
Adequate organ function within 7 days before study intervention
Provide written informed consent
Women of childbearing potential must agree to use contraception from 14 days before randomization through specified periods after last doses
Women must be postmenopausal, surgically sterile, or have a condition preventing childbearing
You will not qualify if you...
Prior treatment with any PARP inhibitor
Known allergy to nesuparib, pembrolizumab, or chemotherapy components
MMR deficiency confirmed by local testing
Receiving cancer-directed study therapy or investigational agent within 4 weeks before randomization
Active central nervous system metastases or carcinomatous meningitis unless stable after treatment
Known additional malignancy requiring treatment within last 2 years except certain skin and cervical cancers
Live vaccine within 30 days before first study dose
Diagnosis of immunodeficiency or recent systemic immunosuppressive therapy
History of pneumonitis requiring steroids or current pneumonitis
Uncontrolled illness including infection, lung disease, heart failure, angina, arrhythmia, or psychiatric/social issues
Known HIV infection
History or active Hepatitis B or C infection
Unable to swallow oral medication or gastrointestinal disorders affecting absorption
History or current diagnosis of myelodysplastic syndrome or acute myeloid leukemia
Systemic autoimmune diseases such as lupus
Not recovered from major surgery or ongoing surgical complications
Conditions or therapies that may interfere with study participation
Psychiatric or substance abuse disorders interfering with trial cooperation
Pregnant, breastfeeding, or planning pregnancy during study and follow-up periods
Prior allogenic tissue or solid organ transplant
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Up to approximately 12 months (6 cycles of chemotherapy followed by up to 14 cycles of maintenance treatment)
Participants receive chemotherapy with pembrolizumab, paclitaxel, and carboplatin for up to 6 cycles, followed by maintenance treatment with pembrolizumab with or without nesuparib for up to 14 cycles.
1 visit every 3 weeks during chemotherapy and 1 visit every 6 weeks during maintenance treatment
Follow-up
Duration - Up to 18 months after enrollment
Participants are monitored for progression-free survival and overall survival after completion of treatment.
Visits at 3, 6, 9, 12, and 18 months after enrollment
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).