Endometrial Cancer Clinical Trials

∙ Participants are eligible to be included in the study only if all of the following criteria apply:

• Is at least 18 years of age and the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the Informed consent form (ICF).

• Has histologically confirmed endometrial carcinoma including but not limited to endometroid, serous, clear cell, and endometrial carcinosarcoma. Mixed epithelial carcinomas are permitted.

• Has undergone at least 1 and no more than 2 lines of prior systemic treatment for EC. Up to 3 lines of prior systemic treatment are acceptable if one line was administered in the adjuvant/neo-adjuvant setting. The definition of prior lines of therapy is as follows:

‣ Adjuvant ± neo-adjuvant therapy counts as one line of treatment.

⁃ Maintenance therapy is considered part of the preceding line and does not count as an independent line.

⁃ Switching to another agent within the same class due to toxicity (without disease progression) is considered part of the same line of therapy.

⁃ Unplanned addition or switching to a new anti-cancer therapy in a different class is considered a separate line of therapy.

⁃ Hormonal therapy is NOT counted as a separate line.

• Must have progressed on or after prior platinum-based chemotherapy and have received anti- Programmed cell death 1 (PD-1) /anti- Programmed cell death ligand 1 (PD-L1) therapy, either separately or in combination. Participants deemed unsuitable for a prior PD-1/PD-L1 inhibitor therapy (contraindications such as immunodeficiency, autoimmune disease that required systemic treatment) as determined by the investigator or treating physician are eligible.

• Participants must have a platinum-free interval of less than 12 months if they previously received platinum-based therapy solely in the adjuvant setting. The platinum-free interval is defined as the date of the last dose of platinum-based chemotherapy to the date of disease progression.

‣ If PD-L1/PD-1 inhibitor therapy was administered with platinum-based treatment, participant is eligible regardless of whether the Platinum-free interval (PFI) exceeds 12 months.

⁃ Participants with metastatic disease who underwent treatment including gynecological surgery followed by a platinum-based regimen, or those deemed intolerant to platinum-based therapy, are eligible regardless of whether the PFI exceeds 12 months.

• Has provided a Formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample sufficient for the central assessment of B7 homolog 4 protein (B7-H4) expression, with the result of B7-H4 expression testing available prior to date of randomization.

• Has ≥1 Target Lesion per RECIST 1.1 by BICR eligibility review of screening scans.

• Is willing to use adequate contraception. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:

‣ Is a Participant of non-childbearing potential (PONCBP) OR

⁃ Is a Participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, 30 days prior to Cycle 1 Day 1 (C1D1) and during the study intervention period and for at least 8 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.

• A POCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention

‣ If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

⁃ Additional requirements for pregnancy testing during and after study intervention are described in protocol.

⁃ The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a participant with an early undetected pregnancy.

• Is capable of giving signed informed consent including compliance with the requirements and restrictions listed in the ICF and in the protocol.

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Has adequate organ function.