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

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 \<1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) beginning at the time of informed consent, during the study treatment, and for at least 210 days after the last dose of study drug. During this period, the participant agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during this period for the purpose of reproduction. \- The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed. \- Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) 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 in Section 8.3.5. \- Abstains from breastfeeding during the study intervention period and for at least 10 days after study intervention. \- Medical history, menstrual history, and recent sexual activity have been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy. Informed Consent 10. The participant provides written informed consent for the study. Additional Categories 11. Has provided an archival tumor tissue sample (slides or block) for pathologic confirmation of diagnosis at Tufts Medical Center. 12. Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (except for alopecia and vitiligo). Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible. 13. Adequate organ function as defined in protocol Table 3. Specimens must be collected within 10 days before the start of study intervention. 14. Any other medical condition that will prevent the safe administration of study drugs in the opinion of the treating physician. 15. Be willing and able to comply with study procedures, laboratory tests, and other requirements of the study. 16. HIV-infected participants must have well-controlled HIV on ART, defined as: a. Having a CD4+ T-cell count ≥350 cells/mm3 at the time of screening b. Having achieved and maintained virologic suppression, defined as confirmed HIV RNA level below 50 or the LLOQ using the locally available assay, at the time of screening and for at least 12 weeks before screening. c. Absence of any AIDS-defining opportunistic infections within the past 12 months d. Being on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before randomization and agreeing to continue ART throughout the study Note: The ART regimen must not contain any antiretroviral medications that are strong CYP3A4 inducers/inhibitors/substrates. Refer to https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Please note that this list is not exhaustive and that investigators should review the locally-approved label for all concomitant therapy to ensure it is not a strong inducer/inhibitor/substrate of CYP3A4. HIV testing at screening is not otherwise required. 17. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization. Note: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.