Safety and Efficacy of Retifanlimab (INCMGA00012) Alone or in Combination With Other Therapies in Participants With Advanced or Metastatic Endometrial Cancer Who Have Progressed on or After Platinum-based Chemotherapy.
- Conditions
- Endometrial Cancer
- Interventions
- Registration Number
- NCT04463771
- Lead Sponsor
- Incyte Corporation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 300
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group E - retifanlimab + epacadostat epacadostat Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat Group C - retifanlimab + epacadostat retifanlimab Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat (IDO1 inhibitor) Group C - retifanlimab + epacadostat epacadostat Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat (IDO1 inhibitor) Group A - retifanlimab retifanlimab Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously Group F - retifanlimab + INCAGN02385 and INCAGN02390 INCAGN02385 Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab in combination with INCAGN02385 and INCAGN02390 intravenously Group F - retifanlimab + INCAGN02385 and INCAGN02390 INCAGN02390 Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab in combination with INCAGN02385 and INCAGN02390 intravenously Group E - retifanlimab + epacadostat retifanlimab Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat Group B - retifanlimab retifanlimab Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously Group D - retifanlimab + pemigatinib retifanlimab Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral pemigatininb (FGFR 1,2,3 inhibitor) Group D - retifanlimab + pemigatinib pemigatinib Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral pemigatininb (FGFR 1,2,3 inhibitor)
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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 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.
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.
Trial Locations
- Locations (65)
Advent Health Medical Group-Orlando 2501
🇺🇸Orlando, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute Hospital
🇺🇸Tampa, Florida, United States
Alaska Womens Cancer Care Akwcc
🇺🇸Anchorage, Alaska, United States
Honorhealth
🇺🇸Phoenix, Arizona, United States
Arizona Oncology Associates
🇺🇸Tucson, Arizona, United States
UCLA Medical Hematology & Oncology
🇺🇸Los Angeles, California, United States
Olive View Med Ctr
🇺🇸Sylmar, California, United States
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Mount Sinai Medical Center Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
Barbara Ann Karmanos Cancer Hospital
🇺🇸Detroit, Michigan, United States
Minnesota Oncology-Maplewood
🇺🇸Coon Rapids, Minnesota, United States
Midwest Cancer Care
🇺🇸Kansas City, Missouri, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Henderson, Nevada, United States
New Mexico Cancer Care Alliance
🇺🇸Albuquerque, New Mexico, United States
Laura & Isaac Perlmutter Cancer Ctr
🇺🇸New York, New York, United States
University of North Carolina At Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
The Ohio State University Wexner Medical Center Division of Gynecologic Oncology
🇺🇸Hilliard, Ohio, United States
Willamette Valley Cancer Institute
🇺🇸Eugene, Oregon, United States
Texas Oncology-Tyler
🇺🇸Sioux Falls, South Dakota, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Texas Oncology-Austin Center
🇺🇸Austin, Texas, United States
Texas Oncology-Fort Worth South Henderson
🇺🇸Fort Worth, Texas, United States
Texas Oncology San Antonio
🇺🇸San Antonio, Texas, United States
Texas Oncology the Woodlands
🇺🇸Shenandoah, Texas, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
O.L.V Ziekenhuis
🇧🇪Aalst, Belgium
Institut Jules Bordet
🇧🇪Brussels, Belgium
Ghent University Hospital
🇧🇪Gent, Belgium
Universitaire Ziekenhuis Leuven - Gasthuisberg
🇧🇪Leuven, Belgium
Centre Hospitalier Universitaire de Liege - Sart Tilman
🇧🇪Liège, Belgium
Chu Ucl Namur de Saint Elisabeth
🇧🇪Namur, Belgium
Chu Besancon Hospital Jean Minjoz
🇫🇷Besancon, France
Institut Bergonie
🇫🇷Bordeaux Cedex, France
Hospital Cochin Cancerologie
🇫🇷Paris, France
Cario - Centre Armoricain de Radiotherapie Imagerie Medicale Et Oncologie
🇫🇷Plérin, France
Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
🇫🇷Saint Herblain, France
Institut Gustave Roussy
🇫🇷Villejuif Cedex, France
High Technology Hospital Medcenter
🇬🇪Batumi, Georgia
Jsc Evex Hospitals
🇬🇪Kutaisi, Georgia
Todua Clinic, Llc
🇬🇪Tbilisi, Georgia
Caucasus Medical Centre Llc
🇬🇪Tbilisi, Georgia
INNOVA
🇬🇪Tbilisi, Georgia
Multiprofile Clinic Consilium Medulla Llc
🇬🇪Tbilisi, Georgia
Charite - Campus Virchow-Klinikum
🇩🇪Berlin, Germany
University Clinic Carl Gustav Carus Technical University Dresden
🇩🇪Dresden, Germany
Klinikum Kassel Gmbh
🇩🇪Kassel, Germany
Universitarsfrauenklinik Ulm
🇩🇪ULM, Germany
Alexandra General Hospital of Athens
🇬🇷Athens, Greece
University Hospital of West Attica - Attikon
🇬🇷Athens, Greece
Hygeia Hospital
🇬🇷Marousi, Greece
Euromedica General Clinic of Thessaloniki
🇬🇷Thessaloniki, Greece
Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - Malpighi
🇮🇹Bologna, Italy
Presidio Ospedaliero Di Summa Antonio Perrino
🇮🇹Brindisi, Italy
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori
🇮🇹Meldola, Italy
Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
🇮🇹Milano, Italy
Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano
🇮🇹Milano, Italy
European Institute of Oncology
🇮🇹Milano, Italy
Istituto Nazionale Tumori Irccs Fondazione Pascale
🇮🇹Napoli, Italy
Iov - Istituto Oncologico Veneto Irccs
🇮🇹Padova, Italy
Fondazione Policlinico Universitario Agostino Gemelli Irccs
🇮🇹Roma, Italy
Ospedale Santa Maria Ca Foncello
🇮🇹Treviso, Italy