A Phase 3 Randomized, Open-label, Active-comparator Controlled Clinical Study of Pembrolizumab versus Platinum Doublet Chemotherapy in Participants With Mismatch Repair Deficient (dMMR) Advanced or Recurrent Endometrial Carcinoma in the First-line Setting (KEYNOTE-C93/GOG-3064/ENGOT-en15)
- Conditions
- endometrial carcinomauterus cancer10038594
- Registration Number
- NL-OMON53504
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 24
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 except as noted
below: * May have received 1 prior line of systemic platinum-based adjuvant
and/or neoadjuvant chemotherapy in the setting of curative-intent resection if
the recurrence occurred =6 months after the last dose of chemotherapy. * May
have received prior radiation with or without radiosensitizing chemotherapy if
>2 weeks before the start of study intervention * May have received prior
hormonal therapy for treatment of EC, provided that it was discontinued =1 week
prior to randomization 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 s
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.
5.5.Has received prior systemic anticancer therapy including investigational
agents for advanced or metastatic EC.
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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>1. PFS: The time from randomization to the first documented disease progression<br /><br>or death due to any cause, whichever occurs first.<br /><br>2. OS: The time from randomization to death due to any cause. </p><br>
- Secondary Outcome Measures
Name Time Method