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.

Conditions: Endometrial Cancer

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.

Keywords: endometrial carcinoma endometrium cancer neoplasms endometrial advanced metastatic pd-1 pd-l1 retifanlimab incmga0012 incagn02385 incagn02390 podium lag-3 tim-3