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.

Endometrial Cancer Clinical Trial

— POD1UM-204  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04463771
• Other study ID #: INCMGA 0012-204
• Status: Recruiting
• Phase: Phase 2
• Start date: January 26, 2021
• Est. completion date: May 31, 2026

Study information

• Verified date: June 2024
• Source: Incyte Corporation
• Contact: Incyte Corporation Call Center (US)
• Phone: 1.855.463.3463
• Email: medinfo[@]incyte.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: May 31, 2026
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• retifanlimab
INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.
• epacadostat
epacadostat will be administered orally BID.
• pemigatinib
pemigatinib will be administered orally QD.
• INCAGN02385
INCAGN2385 will be administered every 2 weeks
• INCAGN02390
INCAGN2390 will be administered every 2 weeks

Locations

Country	Name	City	State
Belgium	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
China	Beijing Cancer Hospital	Beijing
China	The Affiliated Drum Tower Hospital of Nanjing University	Nanjing
France	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
Georgia	High Technology Hospital Medcenter	Batumi
Georgia	Jsc Evex Hospitals	Kutaisi
Georgia	Caucasus Medical Centre Llc	Tbilisi
Georgia	INNOVA	Tbilisi
Georgia	Multiprofile Clinic Consilium Medulla Llc	Tbilisi
Georgia	Todua Clinic, Llc	Tbilisi
Germany	Charite - Campus Virchow-Klinikum	Berlin
Germany	University Clinic Carl Gustav Carus Technical University Dresden	Dresden
Germany	Klinikum Kassel Gmbh	Kassel
Germany	Universitarsfrauenklinik Ulm	ULM
Greece	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
Italy	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	Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano	Milano
Italy	European Institute of Oncology	Milano
Italy	Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele	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
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	Alaska Womens Cancer Care Akwcc	Anchorage	Alaska
United States	Georgia Cancer Center	Augusta	Georgia
United States	Texas Oncology-Austin Center	Austin	Texas
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of North Carolina At Chapel Hill	Chapel Hill	North Carolina
United States	Barbara Ann Karmanos Cancer Hospital	Detroit	Michigan
United States	Willamette Valley Cancer Institute	Eugene	Oregon
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Texas Oncology-Fort Worth South Henderson	Fort Worth	Texas
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	The Ohio State University Wexner Medical Center Division of Gynecologic Oncology	Hilliard	Ohio
United States	Midwest Cancer Care	Kansas City	Missouri
United States	UCLA Medical Hematology & Oncology	Los Angeles	California
United States	Miami Cancer Institute	Miami	Florida
United States	Mount Sinai Medical Center Comprehensive Cancer Center	Miami Beach	Florida
United States	Minnesota Oncology-Maplewood	Minneapolis	Minnesota
United States	Tennessee Oncology	Nashville	Tennessee
United States	Laura & Isaac Perlmutter Cancer Ctr	New York	New York
United States	Advent Health Medical Group-Orlando 2501	Orlando	Florida
United States	Honorhealth	Phoenix	Arizona
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University	Saint Louis	Missouri
United States	Texas Oncology San Antonio	San Antonio	Texas
United States	Texas Oncology the Woodlands	Shenandoah	Texas
United States	Texas Oncology-Tyler	Sioux Falls	South Dakota
United States	Olive View Med Ctr	Sylmar	California
United States	H. Lee Moffitt Cancer Center and Research Institute Hospital	Tampa	Florida
United States	Arizona Oncology Associates	Tucson	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
Incyte Corporation	European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation

Countries where clinical trial is conducted

United States,  Belgium,  China,  France,  Georgia,  Germany,  Greece,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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