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: Enrolling; 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: 300 estimated 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)

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300 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