Clinical trial NCT04463771: 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.
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Endometrial Cancer
Keywords: Endometrial Carcinoma
Endometrium Cancer
Neoplasms Endometrial
Advanced
Metastatic
PD-1
PD-L1
retifanlimab
INCMGA0012
INCAGN02385
INCAGN02390
PODIUM
LAG-3
TIM-3
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
Collaborators: name: GOG Foundation
name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
First posted: 2020-07-09
Enrollment: 206
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Group A - Objective Response Rate
timeFrame: up to 2.5 years
Secondary outcomes:
measure: Group A -Duration of Response
timeFrame: up to 2.5 years
measure: Group A - Disease Control Rate
timeFrame: up to 2.5 years
measure: Group A - Overall Survival
timeFrame: up to 3.5 years
measure: Group A - Progression Free Survival
timeFrame: up to 3.5 years
measure: Group B -Duration of Response
timeFrame: up to 2.5 years
measure: Group B - Disease Control Rate
timeFrame: up to 2.5 years
measure: Group B - Overall Survival
timeFrame: up to 3.5 years
measure: Groups B - Objective Response Rate
timeFrame: up to 2 years
measure: Group B - Progression Free Survival
timeFrame: up to 3.5 years
measure: Groups C, D, E and F - Objective Response Rate
timeFrame: up to 2 years
measure: Number of Treatment-Related Adverse Events
timeFrame: up to 4 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Womens Cancer Care Akwcc
state: Alaska
city: Phoenix
country: United States
facility: Honorhealth
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Medical Hematology & Oncology
state: California
city: Sylmar
country: United States
facility: Olive View Med Ctr
state: California
city: Fort Lauderdale
country: United States
facility: Broward Health Medical Center
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Advent Health Medical Group-Orlando 2501
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute Hospital
state: Florida
city: Augusta
country: United States
facility: Georgia Cancer Center
state: Georgia
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Hospital
state: Michigan
city: Coon Rapids
country: United States
facility: Minnesota Oncology-Maplewood
state: Minnesota
city: Kansas City
country: United States
facility: Midwest Cancer Care
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Ctr
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina At Chapel Hill
state: North Carolina
city: Hilliard
country: United States
facility: The Ohio State University Wexner Medical Center Division of Gynecologic Oncology
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute
state: Oregon
city: Sioux Falls
country: United States
facility: Texas Oncology-Tyler
state: South Dakota
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-Austin Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Fort Worth South Henderson
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology San Antonio
state: Texas
city: Shenandoah
country: United States
facility: Texas Oncology the Woodlands
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Aalst
country: Belgium
facility: O.L.V Ziekenhuis
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Gent
country: Belgium
facility: Ghent University Hospital
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuis Leuven - Gasthuisberg
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liege - Sart Tilman
city: Namur
country: Belgium
facility: Chu Ucl Namur de Saint Elisabeth
city: Besancon
country: France
facility: Chu Besancon Hospital Jean Minjoz
city: Bordeaux Cedex
country: France
facility: Institut Bergonie
city: Paris
country: France
facility: Hospital Cochin Cancerologie
city: Plérin
country: France
facility: Cario - Centre Armoricain de Radiotherapie Imagerie Medicale Et Oncologie
city: Saint Herblain
country: France
facility: Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Batumi
country: Georgia
facility: High Technology Hospital Medcenter
city: Kutaisi
country: Georgia
facility: Jsc Evex Hospitals
city: Tbilisi
country: Georgia
facility: Todua Clinic, Llc
city: Tbilisi
country: Georgia
facility: Caucasus Medical Centre Llc
city: Tbilisi
country: Georgia
facility: INNOVA
city: Tbilisi
country: Georgia
facility: Multiprofile Clinic Consilium Medulla Llc
city: Berlin
country: Germany
facility: Charite - Campus Virchow-Klinikum
city: Dresden
country: Germany
facility: University Clinic Carl Gustav Carus Technical University Dresden
city: Kassel
country: Germany
facility: Klinikum Kassel Gmbh
city: ULM
country: Germany
facility: Universitarsfrauenklinik Ulm
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens
city: Athens
country: Greece
facility: University Hospital of West Attica - Attikon
city: Marousi
country: Greece
facility: Hygeia Hospital
city: Thessaloniki
country: Greece
facility: Euromedica General Clinic of Thessaloniki
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - Malpighi
city: Brindisi
country: Italy
facility: Presidio Ospedaliero Di Summa Antonio Perrino
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori
city: Milano
country: Italy
facility: Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
city: Milano
country: Italy
facility: Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano
city: Milano
country: Italy
facility: European Institute of Oncology
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione Pascale
city: Padova
country: Italy
facility: Iov - Istituto Oncologico Veneto Irccs
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli Irccs
city: Treviso
country: Italy
facility: Ospedale Santa Maria Ca Foncello
Study officials:
affiliation: Incyte Corporation
name: Mark Cornfield
role: STUDY_DIRECTOR
References: