Endometrial Cancer
Conditions
Keywords
Endometrial Carcinoma, Endometrium Cancer, Neoplasms Endometrial, Advanced, Metastatic, PD-1, PD-L1, retifanlimab, INCMGA0012, INCAGN02385, INCAGN02390, PODIUM, LAG-3, TIM-3
Brief summary
This is a multicenter, open-label, nonrandomized, Phase 2 umbrella study of retifanlimab in participants who have advanced or metastatic endometrial cancer that has progressed on or after platinum-based chemotherapy. retifanlimab will be administered as monotherapy or in combination with other immunotherapy or targeted agents.
Interventions
DRUGretifanlimab
INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.
DRUGepacadostat
epacadostat will be administered orally BID.
DRUGpemigatinib
pemigatinib will be administered orally QD.
DRUGINCAGN02385
INCAGN2385 will be administered every 2 weeks
DRUGINCAGN02390
INCAGN2390 will be administered every 2 weeks
Sponsors
GOG Foundation
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to comprehend and willingness to sign a written ICF for the study. Note for Germany: This excludes individuals who are housed in an institution due to official or court order Women 18 years of age or older (or as applicable per local country requirements). * Histologically confirmed diagnosis of advanced or metastatic endometrial cancer with disease progression on or after treatment with at least 1 platinum-containing regimen for advanced or metastatic disease. * Groups A, B, and E: Have not been previously treated with a PD-(L)1 inhibitor. * Group A only: Tumor tissue tested as MSI-High * Group B only: Tumor tissue tested as deficient MMR or an ultra-mutated POLE tumor. * Group D only: Tumor tissue tested as having an FGFR 1,2,3 mutation or alteration characterized as per protocol. * Group E: Tumor tissue tested as MSS and PD-L1 positive. * Group F: Radiological evidence of disease progression on or after prior PD (L)1 therapy and Tumor tissue tested as MSI-H * Must have at least 1 measurable tumor lesion per RECIST v1.1. * Willing to provide tumor tissue sample (fresh or archived). * ECOG performance status 0 to 1. * Willingness to avoid pregnancy.
Exclusion criteria
* Group A, B and E only: Histologically confirmed diagnosis of carcinosarcoma of the uterus. * Histologically confirmed diagnosis of sarcoma of the uterus. * Has disease eligible for potentially curative treatment. * Receipt of anticancer therapy within 28 days of the first administration of study treatment, with the exception of localized radiotherapy. * Toxicity of prior therapy that has not recovered to ≤ Grade 1 or baseline unless approved by the medical monitor. * Groups C, D and F (combinations): limiting immune-related toxicity during prior checkpoint inhibitor therapy. * Group F only: Previous treatment with LAG-# or TIM-3 therapy or lenvatinib; multiple metastases that achieved mixed tumor response to prior anti-PD-(L)1 therapy * Has an active autoimmune disease requiring systemic immunosuppression with corticosteroids (\> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 14 days before the first dose of study treatment. * Receiving chronic systemic steroids (\> 10 mg/day of prednisone or equivalent): * Known active CNS metastases and/or carcinomatous meningitis. * Has known active hepatitis B or C. * Has received a live vaccine within 28 days of the planned start of study treatment. * Evidence of interstitial lung disease or active, noninfectious pneumonitis. * Participants who are known to be HIV-positive with some protocol exceptions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Group A - Objective Response Rate | up to 2.5 years | Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Group A - Disease Control Rate | up to 2.5 years | Defined as the proportion of participants with CR, PR, or SD (as determined by ICR) as best response. |
| Group A - Overall Survival | up to 3.5 years | Defined as the time from the first dose of study treatment until death due to any cause. |
| Group A - Progression Free Survival | up to 3.5 years | Defined as the time from the first dose of study treatment until disease progression (as determined by ICR) or death due to any cause. |
| Group B -Duration of Response | up to 2.5 years | Defined as the time from the first documented objective response (CR or PR) according to RECIST v1.1 (as determined by ICR) until disease progression or death due to any cause. |
| Group B - Disease Control Rate | up to 2.5 years | Defined as the proportion of participants with CR, PR, or SD (as determined by ICR) as best response. |
| Group A -Duration of Response | up to 2.5 years | Defined as the time from the first documented objective response (CR or PR) according to RECIST v1.1 (as determined by ICR) until disease progression or death due to any cause. |
| Groups B - Objective Response Rate | up to 2 years | Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee |
| Group B - Progression Free Survival | up to 3.5 years | Defined as the time from the first dose of study treatment until disease progression (as determined by ICR) or death due to any cause. |
| Groups C, D, E and F - Objective Response Rate | up to 2 years | Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee |
| Number of Treatment-Related Adverse Events | up to 4 years | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment. |
| Group B - Overall Survival | up to 3.5 years | Defined as the time from the first dose of study treatment until death due to any cause. |
Countries
Belgium, France, Georgia, Germany, Greece, Italy, United States
Outcome results
None listed