Endometrial Cancer Clinical Trials

• Female patient of age ≥18 years.

• Recurrent and progressive endometrial cancer, all stages at primary diagnosis. The histology types will be pending the preclinical assessments, but can include:

∙ Endometrioid endometrial carcinoma

‣ Serous endometrial carcinoma

• Prior standard of care of surgical intervention, including hysterectomy.

• Evidence of disease progression on or following the most recent line of therapy prior to screening. Therapy must include platinum-based chemotherapy. If the patient is eligible for immunotherapy, this must have been provided. Patient may have received either radiation therapy or hormone therapy, neither of which will be considered a line of therapy. Chemotherapy during radiotherapy will not be considered a line of therapy.

• Maximum of three prior lines of therapy. Neo-adjuvant and postsurgical therapy, if provided, will be counted as 1 line of therapy. Therapy given in a maintenance fashion after primary treatment will not be counted as a line of therapy.

• IHC expression of nectin-4.

• Toxicity from prior treatment recovered to G1 or G0.

• ECOG status of 1 or 0.

• At least 1 measurable target lesion according to RECIST v1.1, including the following criteria:

∙ Non-nodal lesion that measures ≥ 1.0 cm in the longest diameter.

‣ Lymph node (LN) lesion that measures as ≥ 1.5 cm in the short axis.

‣ The lesion is suitable for repeat measurement using computed tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of subsequent growth after treatment.

⁃ Documented tumor status for MSI and MMR.

⁃ In the opinion of the investigator, the patient must have a life expectancy of at least 12 weeks and be well enough to receive experimental therapy.

⁃ Adequate organ function as determined by laboratory tests defined in the table below at screening.

⁃ Hematological: Absolutely neutrophil count (ANC)≥ 1500/μL, Platelets ≥ 100,000/μL, Hemoglobin ≥ 9.0 g/dL or 5.6 mmol/L, No erythropoietin dependency or packed red blood cell transfusion within last 2 weeks.

⁃ Renal: Creatinine, OR ≤ 1.5 x ULN, Creatinine clearance as calculated per institutional standard ≥ 30 mL/min for patients with creatinine \> 1.5 × institutional ULN Hepatic: Total bilirubin ≤ 1.5 × upper limit of normal (ULN) ≤ 3 ULN for participants with Gilbert's syndrome. AST, ALT ≤ 3 × ULN (≤ 5 × ULN for participants with liver metastases

⁃ Ability to understand a written informed consent document, and the willingness to sign it.

⁃ Pregnancy: It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Nonsterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below. Female patients must meet one of the following:

• Postmenopausal for at least one year before the screening visit, or

∙ Surgically sterile, or

∙ If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through three months after the last dose of study drug, AND

∙ Must also adhere to the guidelines of any treatment specific pregnancy prevention program, if applicable, or

∙ Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable contraception methods.) Male patients/partners of patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:

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• Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, OR

∙ Must also adhere to the guidelines of any treatment specific pregnancy prevention program, if applicable, OR

∙ Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.)