Pembrolizumab vs Platinum Doublet Chemotherapy in Participants with dMMR Advanced or Recurrent Endometrial Carcinoma in the First-line Setting
- Conditions
- First-line treatment of participants with dMMR advanced or recurrent ECMedDRA version: 21.1Level: LLTClassification code 10014747Term: Endometrial carcinoma recurrentSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-003185-12-NO
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 280
1.Has a histologically confirmed diagnosis of inoperable, Stage III/IV, persistent or recurrent EC or carcinosarcoma (mixed Mullerian tumor)
that is centrally confirmed as dMMR.
2.Has radiographically evaluable disease, either measurable or nonmeasurable per RECIST 1.1, as assessed by the investigator.
Prior Therapy
3.Has received no prior systemic therapy for EC.
4.Is female, at least 18 years of age at the time of providing the informed consent (either Authorization for Release of Tumor Tissue or main study consent).
5.Has ECOG performance status of 0 or 1 within 7 days before randomization.
6.A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
-Is not a WOCBP
OR
-Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows:
- Pembrolizumab (120 days after last dose)
- Chemotherapy (180 days after last dose)
The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study intervention.
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) as required by local regulations) within 24 hours for urine or 72 hours for serum before the first dose of study intervention.
If a urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Additional requirements for pregnancy testing during and after study intervention must adhere to protocol.
Abstains from breastfeeding during the study intervention period and for at least 120 days after the last dose of pembrolizumab, 30 days after the
last dose of cytotoxic chemotherapy agents (paclitaxel, docetaxel, carboplatin, cisplatin), or as per local regulations.
The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
7.The participant (or legally acceptable representative) has provided documented informed consent/assent for the study. The participant may also provide consent/assent for FBR. However, the participant may participate in the study without participating in FBR.
8.Provides an archival tumor tissue sample or newly obtained (core, incisional, or excisional) biopsy of a tumor lesion not previously irradiated for verification of dMMR status and histology.
9.If HBsAg positive is eligible if they have received HBV antiviral therapy for at least 4 weeks and has u
1.Has uterine mesenchymal tumor such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas. Adenosarcomas are also not allowed. Neuroendocrine tumors are also not allowed.
2.Has EC of any histology that is pMMR.
3.Is a candidate for curative-intent surgery or curative-intent radiotherapy.
4.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
5.Has received prior systemic anticancer therapy including investigational agents for EC. This includes any chemotherapy given for EC other than as a radiosensitizer.
6.Has had a major operation and has not recovered adequately from the procedure and/or any complications from the operation before starting study intervention.
7.Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
8.Is currently participating in or has participated in a study of an investigational agent for EC; or has participated in a study of an investigational agent for non-EC within 4 weeks before the first dose of study intervention; or has used an investigational device within 4 weeks before the first dose of study intervention.
9.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
10.Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
11.Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days before the first dose of study intervention.
12.Has a known intolerance to any study intervention and/or any of its excipients.
13.Has an active autoimmune disease that has required systemic treatment in past 2 years.
14.Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
15.Has an active infection, requiring systemic therapy.
16.Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority.
Refer to the protocol for country-specific requirements.
17. Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
18.Has had an allogenic tissue/solid organ transplant. Refer to the protocol for country-specific requirements.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method