Gynecological Cancer
GOG-3119/TroFuse-033/ENGOT-en29: sac-TMT Plus Pembrolizumab as 1L Maintenance in pMMR Endometrial Cancer
Description
This is a Phase 3, randomized, active-controlled, parallel-group, open-label, multicenter study of induction with pembrolizumab and chemotherapy followed by maintenance with sac-TMT plus pembrolizumab versus pembrolizumab alone in participants with primary advanced or recurrent pMMR endometrial carcinoma who have not received treatment with chemotherapy and/or anti-PD-1/PD-L1 in the first line for advanced or metastatic disease.
The purpose of the study is to compare maintenance treatment with sac-TMT plus pembrolizumab with pembrolizumab alone with respect to the dual primary objectives of PFS per RECIST 1.1 as assessed by BICR and OS in the Maintenance part of the study. Both primary objectives will be evaluated in participants with medium + high TROP2 expressing tumors and in all participants. Approximately 1123 participants will be enrolled in the Induction part of the study to ensure that 842 participants without disease progression can be randomized to the Maintenance part of the study. There are no study objectives for Induction. In addition, participants who have disease progression per RECIST 1.1 as determined by the investigator and subsequently verified by BICR during or after completion of Induction (and are therefore not eligible for Maintenance) may be randomized to receive sac-TMT plus pembrolizumab or sac-TMT alone in the Subsequent Treatment part of the study. PFS (per RECIST 1.1 as assessed by BICR), OS, OR, and DOR will be evaluated as exploratory objectives in the Subsequent Treatment part of the study.
Inclusion Notes
For a full description of this trial, please go to the listing on www.clinicaltrials.gov.
For Medical Professionals
An individual is eligible for inclusion in the study if the individual meets all of the following criteria:
Type of Participant and Disease Characteristics
- The participant must have a histologically confirmed diagnosis of primary advanced or recurrent endometrial carcinoma that has been confirmed as pMMR by local pathology.
Note: The local pMMR assay by immunohistochemistry should assess MSH6, PMS2, MSH2, and MLH1. pMMR is defined as all 4 proteins expressed.
- Has radiographically evaluable disease, with measurable Stage III or either measurable or non-measurable Stage IV or recurrent disease per RECIST 1.1, as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
Note: Participants with fluid-only disease (eg, pleural effusion or ascites, and no other radiographically apparent lesions) must have cytologic confirmation of malignancy. Prior Therapy
- Has received no prior systemic therapy for endometrial carcinoma 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. This prior chemotherapy
may have been given as treatment involving chemotherapy alone, concurrent
chemoradiation, or as part of a sequential approach such as in a regimen involving
concurrent chemoradiation followed by chemotherapy.
- Instances in which both adjuvant and neoadjuvant systemic platinum-based chemotherapy are used will be counted as one line of chemotherapy
- May have received prior radiation with or without radiosensitizing chemotherapy if >2 weeks before the start of induction treatment (see also Section 5.2). Participants must have recovered adequately from all radiation-related toxicities (as determined by the investigator), not require systemic corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- May have received prior hormonal therapy for treatment of endometrial carcinoma, provided that it was discontinued ≥1 week before the start of induction treatment.
- May have received 1 prior line of systemic platinum-based adjuvant and/or
neoadjuvant chemotherapy in the setting of curative-intent. This prior chemotherapy
may have been given as treatment involving chemotherapy alone, concurrent
chemoradiation, or as part of a sequential approach such as in a regimen involving
concurrent chemoradiation followed by chemotherapy.
- Is assigned female sex at birth, at least 18 years of age, at the time of providing the informed consent. Follow local regulatory requirements if the legal age of consent for participation is >18 years of age.
Assigned Female Sex at Birth
- A participant assigned female sex at birth is eligible to participate if not breastfeeding during the study intervention period and for at least 120 days after the last dose of study intervention.
- A POCBP is eligible to participate if not pregnant and if a negative highly sensitive pregnancy test (urine or serum), as required by local regulations, has been obtained within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. Additional requirements for pregnancy testing during and after study intervention are in Section 8.3.5.
- A POCBP is eligible to participate if they use a contraceptive method that is highly
effective (with a failure rate of <1% per year), with low user dependency, or if they
adhere to penile-vaginal intercourse abstinence as their preferred and usual lifestyle
(abstinent on a long-term and persistent basis), as described in Appendix 5, during the
intervention period and for at least the time needed to eliminate each study intervention
after the last dose of study intervention. In addition, the participant agrees not to donate
eggs (ova, oocytes) to others or freeze/store eggs during this period for the purpose of
reproduction. The length of time required to continue contraception for each study
intervention is:
- Sac-TMT: 210 days
- Pembrolizumab: 120 days
- Carboplatin and paclitaxel: 190 days
Informed Consent
- The participant has provided documented informed consent for the study.
Note: References to “legally acceptable representative” for consenting purposes are not applicable in the EEA. Individuals in EEA countries who require a legally designated representative for informed consent, as defined by the European Regulation, are not eligible to participate. Individuals in EEA countries who are legally able to consent for themselves but require an Impartial Witness to the consenting process (eg, individuals who are blind, unable to read or write, or unable to sign due to a physical disability) may be enrolled. Investigators must follow local regulations and processes for using an Impartial Witness.
Additional Categories
- Archival tumor tissue sample (the most recent sample is preferred) or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided. Details pertaining to tumor tissue submission can be found in the Central Laboratory Manual.
- Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline (except alopecia or vitiligo). Participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible.
- HIV-infected participants must have well controlled HIV on ART, defined as:
- Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening
- Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening
- It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months
- Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study
- The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers)
- Participants who are HBsAg positive are eligible if they have received HBV antiviral
therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation.
Note: Participants should remain on antiviral therapy throughout study intervention and
follow local guidelines for HBV antiviral therapy post completion of study intervention.
- Hepatitis B screening tests are not required unless:
- Known history of HBV infection
- As mandated by local health authority
- Hepatitis B screening tests are not required unless:
- Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
Note: Participants must have completed curative antiviral therapy at least 4 weeks prior to allocation. Hepatitis C screening tests are not required unless:
- Known history of HCV infection
- As mandated by local health authority
An ECOG performance status of 0 to 1 assessed within 7 days before allocation to Induction.
- Adequate organ function as defined in the following table (Table 1). Specimens must be collected within 7 days before allocation to Induction.
Criteria for All Participants Before Randomization to Either Maintenance or Subsequent Treatment Parts of the Study
- Has an ECOG PS of 0 or 1 as assessed at the Prerandomization Visit (most recent assessment within the visit).
- All AEs (with the exception of alopecia, vitiligo, and Grade ≤2 endocrine-related AEs requiring treatment or hormone replacement) resolved to Grade ≤1 or baseline before randomization.
Note: Participants who permanently discontinue pembrolizumab due to an AE are not eligible for randomization to Maintenance or Subsequent Treatment.
- Has adequate organ function, as indicated by the laboratory values in Table 1 above.
- Criterion Before Randomization Applicable to Maintenance Only: Has a valid TROP2 result from the Central Laboratory test performed during Induction.
Note: TROP2 unknown or unevaluable is not a valid result for randomization to the Maintenance part of the study; however, these participants (without disease progression per RECIST 1.1 as determined by the investigator) are eligible to receive pembrolizumab only as outlined in Section 1.3.2.4 “treatment for patients with unknown or unevaluable TROP2 expression not eligible for maintenance”.
- Criterion Before Randomization Applicable to Maintenance Only: Without disease progression of endometrial carcinoma per RECIST 1.1 as determined by the investigator after completion of study-specified Induction with an evaluable scan at Week 18 (or if a delay in study intervention occurs, the scan result at the time of completion of induction treatment).
- Criterion Before Randomization Applicable to Maintenance Only: Completed induction treatment.
Note: If the participant completed less than 6 cycles or permanently discontinued any treatment during Induction, consultation with the Sponsor is required before randomization.
- Criterion Before Randomization Applicable to Subsequent Treatment Only: Has disease progression of their endometrial carcinoma per RECIST 1.1 as determined by the investigator and subsequently verified by BICR during or after completion of study-specified Induction with an evaluable scan at the time of disease progression (eg, Week 9, Week 18).
Start Date
Tuesday, September 30, 2025
Principal / Contact Name
Sarah Gill, MD