Endometrial Cancer Clinical Trials

• Participant must be able to give signed, written informed consent.

• Participant must have histologically documented, high-grade endometrial cancer. Arms 1 and 2

∙ All high-grade epithelial endometrial histological subtypes are eligible including: endometrioid (Grade 3 only), serous, carcinosarcomas, clear-cell carcinoma, and mixed histologies.

∙ Arm 3

‣ Serous carcinoma or mixed tumors with a majority component of serous carcinoma or carcinosarcoma where the carcinomatous component is serous carcinoma.

• Treatment History Requirements:

• Arms 1 and 2

‣ Subject must have received prior platinum-based chemotherapy

‣ Subject must have received prior anti-PD-(L)1 therapy

‣ Subject must not have received more than three lines of prior systemic therapy Arm 3

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∙ Subject must have received prior platinum-based chemotherapy

‣ Subject must have received prior anti-PD-(L)1 therapy

‣ Subject must not have received more than two lines of prior systemic therapy

• Participant must have histologically confirmed metastatic cancer that has progressed during or after at least 1 prior therapeutic regimen.

• Participant must have at least 1 measurable lesion per RECIST v1.1 criteria (by local Investigator) in a baseline tumor imaging that has been obtained within 28 days of the treatment start. Participant must have radiographic evidence of disease progression based on RECIST v1.1 criteria following the most recent line of treatment.

• Arm 1 and 2 only: Participant must be willing to provide tissue from a newly obtained tumor biopsy from an accessible tumor lesion not previously irradiated after written informed consent.

• Newly obtained is defined as a specimen taken after written informed consent is obtained, during the 28-day Screening period.

• Note: Subjects at EU sites are not eligible for Arm 1 and Arm 2

• Participant must be willing to provide an archival tumor tissue block or at least 20 unstained slides, if available.

• Participant must have stabilized or recovered (Grade 1 or baseline) from all prior therapy related toxicities, except as follows:

∙ Alopecia is accepted.

‣ Endocrine events from prior immunotherapy stabilized at ≤ Grade 2 due to need for replacement therapy are accepted (including hypothyroidism, diabetes mellitus, or adrenal insufficiency).

‣ Neuropathy events from prior cytotoxic therapies stabilized at ≤ Grade 2 are accepted.

• Participant must have an Eastern Cooperative Oncology Group Performance Status 0 or 1.

⁃ Participant must have an estimated life expectancy of longer than 3 months.

⁃ Participant must have adequate organ function at Screening, defined as:

• Absolute neutrophil count \> 1500 cells/µL without growth factor support within 1 week prior to obtaining the hematology values at Screening.

∙ Hemoglobin ≥ 9.0 g/dL.

∙ Platelets ≥ 150,000 cells/µL without transfusion within 1 week prior to obtaining the hematology values at Screening.

∙ Renal function is defined as Glomerular filtration rate (GFR) ≥ 50 mL/min/1.73m2. Note: GFR may be estimated using site standard methods (e.g., CKD-EPI, MDRD, or Cockcroft-Gault) or measured using 24-hour urine collection or Chrome-EDTA clearance, as per site standard practice.

∙ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); ≤ 5 × ULN if liver metastases are present.

∙ Total bilirubin ≤ 1.5 × ULN not associated with Gilbert's syndrome. If associated with Gilbert's syndrome ≤ 3 x ULN is acceptable.

∙ Serum albumin ≥ 3 g/dL.

⁃ Participant must have adequate coagulation profile as defined below if not on anticoagulation. If subject is receiving anticoagulation therapy, then subject must be on a stable dose of anticoagulation for ≥ 1 month:

• Prothrombin time within 1.5 x ULN.

∙ Activated partial thromboplastin time within 1.5 x ULN.