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. (POD1UM-204)

An Umbrella Study of INCMGA00012 Alone and in Combination With Other Therapies in Participants With Advanced or Metastatic Endometrial Cancer Who Have Progressed on or After Platinum-Based Chemotherapy (POD1UM-204)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: retifanlimab; Drug: epacadostat; Drug: pemigatinib; Drug: INCAGN02385; Drug: INCAGN02390

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 09300
    • O.L.V Ziekenhuis
  • Brussels, Belgium, 01000
    • Institut Jules Bordet
  • Ghent, Belgium, 09000
    • Ghent University Hospital
  • Leuven, Belgium, 03000
    • Universitaire Ziekenhuis Leuven - Gasthuisberg
  • Liège, Belgium, 04000
    • Centre Hospitalier Universitaire de Liege - Sart Tilman
  • Namur, Belgium, 05000
    • Chu Ucl Namur de Saint Elisabeth
• France
  • Besançon, France, 25000
    • Chu Besancon Hospital Jean Minjoz
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Paris, France, 75006
    • Hospital Cochin Cancerologie
  • Plérin, France, 22190
    • Cario - Centre Armoricain de Radiotherapie Imagerie Medicale Et Oncologie
  • Saint-Herblain, France, 44800
    • Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Georgia
  • Batumi, Georgia, 06000
    • High Technology Hospital MedCenter
  • Kutaisi, Georgia, 04600
    • Jsc Evex Hospitals
  • Tbilisi, Georgia, 00112
    • Todua Clinic, Llc
  • Tbilisi, Georgia, 00186
    • Caucasus Medical Centre Llc
  • Tbilisi, Georgia, 00186
    • Innova
  • Tbilisi, Georgia, 00186
    • Multiprofile Clinic Consilium Medulla Llc
• Germany
  • Berlin, Germany, 13353
    • Charité - Campus Virchow-Klinikum
  • Dresden, Germany, 01307
    • University Clinic Carl Gustav Carus Technical University Dresden
  • Kassel, Germany, 34125
    • Klinikum Kassel GmbH
  • Ulm, Germany, 89075
    • Universitarsfrauenklinik Ulm
• Greece
  • Athens, Greece, 11528
    • Alexandra General Hospital of Athens
  • Athens, Greece, 12462
    • University Hospital of West Attica - Attikon
  • Marousi, Greece, 15123
    • Hygeia Hospital
  • Thessaloniki, Greece, 54645
    • EUROMEDICA General Clinic of Thessaloniki
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - Malpighi
  • Brindisi, Italy, 72100
    • Presidio Ospedaliero Di Summa Antonio Perrino
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milan, Italy, 20132
    • Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
  • Milan, Italy, 20141
    • European Institute of Oncology
  • Milan, Italy, 20133
    • Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Padua, Italy, 35128
    • Iov - Istituto Oncologico Veneto Irccs
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Treviso, Italy, 31100
    • Ospedale Santa Maria Ca Foncello
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Womens Cancer Care Akwcc
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • HonorHealth
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates
  • California
    • Los Angeles, California, United States, 90048
      • UCLA Medical Hematology & Oncology
    • Sylmar, California, United States, 91342
      • Olive View Med Ctr
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward Health Medical Center
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center Comprehensive Cancer Center
    • Orlando, Florida, United States, 32804
      • Advent Health Medical Group-Orlando 2501
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute Hospital
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Hospital
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Minnesota Oncology-Maplewood
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Midwest Cancer Care
    • St Louis, Missouri, United States, 63110
      • Washington University
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
  • Nevada
    • Henderson, Nevada, United States, 89074
      • Comprehensive Cancer Centers of Nevada
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • New Mexico Cancer Care Alliance
  • New York
    • New York, New York, United States, 10016
      • Laura & Isaac Perlmutter Cancer Ctr
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill
  • Ohio
    • Hilliard, Ohio, United States, 43026
      • The Ohio State University Wexner Medical Center Division of Gynecologic Oncology
  • Oregon
    • Eugene, Oregon, United States, 97401-8122
      • Willamette Valley Cancer Institute
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Texas Oncology-Tyler
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology-Austin Center
    • Fort Worth, Texas, United States, 76104-3902
      • Texas Oncology-Fort Worth South Henderson
    • San Antonio, Texas, United States, 78240
      • Texas Oncology San Antonio
    • Shenandoah, Texas, United States, 77380
      • Texas Oncology the Woodlands
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A - retifanlimab; Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously	Drug: retifanlimab; INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.; Other Names: INCMGA00012
Experimental: Group B - retifanlimab; Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously	Drug: retifanlimab; INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.; Other Names: INCMGA00012
Experimental: Group C - retifanlimab + epacadostat; Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat (IDO1 inhibitor)	Drug: retifanlimab; INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.; Other Names: INCMGA00012; Drug: epacadostat; epacadostat will be administered orally BID.
Experimental: Group D - retifanlimab + 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)	Drug: retifanlimab; INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.; Other Names: INCMGA00012; Drug: pemigatinib; pemigatinib will be administered orally QD.
Experimental: Group E - retifanlimab + epacadostat; Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat	Drug: retifanlimab; INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.; Other Names: INCMGA00012; Drug: epacadostat; epacadostat will be administered orally BID.
Experimental: Group F - retifanlimab + INCAGN02385 and INCAGN02390; Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab in combination with INCAGN02385 and INCAGN02390 intravenously	Drug: INCAGN02385; INCAGN2385 will be administered every 2 weeks; Drug: INCAGN02390; INCAGN2390 will be administered every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group A - Objective Response Rate	Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee	up to 2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group A -Duration of Response	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.	up to 2.5 years
Group A - Disease Control Rate	Defined as the proportion of participants with CR, PR, or SD (as determined by ICR) as best response.	up to 2.5 years
Group A - Overall Survival	Defined as the time from the first dose of study treatment until death due to any cause.	up to 3.5 years
Group A - Progression Free Survival	Defined as the time from the first dose of study treatment until disease progression (as determined by ICR) or death due to any cause.	up to 3.5 years
Group B -Duration of Response	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.	up to 2.5 years
Group B - Disease Control Rate	Defined as the proportion of participants with CR, PR, or SD (as determined by ICR) as best response.	up to 2.5 years
Group B - Overall Survival	Defined as the time from the first dose of study treatment until death due to any cause.	up to 3.5 years
Groups B - Objective Response Rate	Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee	up to 2 years
Group B - Progression Free Survival	Defined as the time from the first dose of study treatment until disease progression (as determined by ICR) or death due to any cause.	up to 3.5 years
Groups C, D, E and F - Objective Response Rate	Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee	up to 2 years
Number of Treatment-Related Adverse Events	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.	up to 4 years

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Collaborators: GOG Foundation; European Network of Gynaecological Oncological Trial Groups (ENGOT)
• Investigators: Study Director: Mark Cornfield, Incyte Corporation

Publications and helpful links

Helpful Links

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2021
• Primary Completion (Estimated): April 14, 2026
• Study Completion (Estimated): July 10, 2026

Study Registration Dates

• First Submitted: July 6, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 9, 2020

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Advanced; Metastatic; PD-1; PD-L1; Endometrial Carcinoma; Endometrium Cancer; Neoplasms Endometrial; retifanlimab; INCMGA0012; INCAGN02385; INCAGN02390; PODIUM; LAG-3; TIM-3
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Neoplastic Processes; Genital Neoplasms, Female; Uterine Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Endometrial Neoplasms; pemigatinib; epacadostat
• Other Study ID Numbers: INCMGA 0012-204; 2020-000496-20 (EudraCT Number); 2022-502600-79-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No