Sacituzumab Tirumotecan +/- Pembrolizumab in I/O Exposed Metastatic or Recurrent Ovarian Clear Cell Cancer

This is a phase II, two-arm, noncomparative screening study of Sacituzumab tirumotecan, an intravenous antibody-drug conjugate (ADC) that targets Trop-1, administered alone or in combination with pembrolizumab, a monoclonal antibody to PD-1 in patients with relapsed clear cell cancers that originated in the ovary, fallopian tube or peritoneal cavity, inclusive of endometriosis (collectively referred to as OCCC throughout the protocol) after previous treatment with anti-PD1 therapy. The regimens will be evaluated separately, and the study is not designed or powered to compare the regimens.

Inclusion Criteria An individual is eligible for inclusion in the study if the individual meets all of the following criteria: Type of Participant and Disease Characteristics 1. Age ≥18 years (at the time of informed consent). 2. Has a histologically-confirmed diagnosis of pure OCCC. Patients with mixed histologies that include a clear cell component will not be eligible for this trial. 3. Has measurable disease per RECIST 1.1 as assessed by the local site investigator/ radiology. Lesions situated in a previously-irradiated area are considered measurable if progression has been shown in such lesions. 4. Patients must have received at least one prior platinum and taxane-based chemotherapy regimen; maintenance treatment will not be counted as a separate regimen. Radiation therapy (including the use of chemotherapy as a radiosensitizer) will not count as a prior systemic regimen. There is otherwise no line limit for entry in to this trial. 5. Patients must have also received one prior line containing an immune checkpoint inhibitor (ICI). More than one prior line of ICI treatment will be exclusionary. 6. Participants with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. 7. ECOG performance status 0-1 8. Is an individual of assigned female sex at birth 9. Participant is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a Person of Child-Bearing Potential (POCBP) OR • Is a POCBP and: \- Agrees to use of a contraceptive method that is highly effective (with a failure rate of \480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the first dose of study intervention. 20\. Is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 21\. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid) 22. History of stem cell/solid organ transplant. Prior/Concomitant Therapy 23. Received prior treatment with a TROP2-targeted ADC. 24. Received prior treatment with a topoisomerase 1 inhibitor-containing ADC. 25. Received prior systemic anticancer therapy within 2 weeks before the first dose of study intervention. 26\. Received prior radiotherapy within 2 weeks before the first dose of study intervention, has radiation-related toxicities, requiring corticosteroids, and/or has radiation pneumonitis. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention. 27\. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. 28\. Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of treatment with study intervention. The required washout period before starting study intervention is 2 weeks. Prior/Concurrent Clinical Study Experience 29. Is currently enrolled on another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited. 30\. Has received an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention. Diagnostic Assessments 31. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of any organ (excluding carcinoma in situ of the bladder) who have undergone potentially curative resection are not excluded. Note: Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA \