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)

Incyte

Status and phase

Active, not recruiting

Phase 2

Conditions

Endometrial Cancer

Treatments

Drug: INCAGN02385

Drug: pemigatinib

Drug: epacadostat

Drug: retifanlimab

Drug: INCAGN02390

Study type

Interventional

Funder types

Other

NETWORK

Industry

Identifiers

NCT04463771

INCMGA 0012-204

Details and patient eligibility

About

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.

Enrollment

206 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

206 participants in 6 patient groups

Group A - retifanlimab

Experimental group

Description:

Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously

Treatment:

Drug: retifanlimab

Group B - retifanlimab

Experimental group

Description:

Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously

Treatment:

Drug: retifanlimab

Group C - retifanlimab + epacadostat

Experimental group

Description:

Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat (IDO1 inhibitor)

Treatment:

Drug: epacadostat

Drug: retifanlimab

Group D - retifanlimab + pemigatinib

Experimental group

Description:

Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral pemigatininb (FGFR 1,2,3 inhibitor)

Treatment:

Drug: retifanlimab

Drug: pemigatinib

Group E - retifanlimab + epacadostat

Experimental group

Description:

Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat

Treatment:

Drug: epacadostat

Drug: retifanlimab

Group F - retifanlimab + INCAGN02385 and INCAGN02390

Experimental group

Description:

Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab in combination with INCAGN02385 and INCAGN02390 intravenously

Treatment:

Drug: INCAGN02390

Drug: INCAGN02385