Inclusion Criteria:
1. Pathologically diagnosed (histological or cytological examination) as clear cell carcinoma of the ovary, fallopian tube, and peritoneum.
* The tumor should be negative for expression of WT-1 antigen and Estrogen Receptor (ER) antigen by immunohistochemistry.
* Tumors with mixed histology will be eligible if \> 50% consists of clear cell carcinoma.
* If diagnosed prior to registration, the timing is not restricted. However, if histological examination was conducted at another institution, the pathological diagnosis must generally be obtained by a pathologist at the study site, e.g., by requesting the pathological specimen.
2. Have received prior systemic therapy that included at least one platinum-containing combination chemotherapy regimen..
3. No active central nervous system (CNS) metastases-including brain metastases, carcinomatous (leptomeningeal) meningitis, or symptomatic spinal metastases that require radiotherapy or surgical intervention.
4. No clinically significant pericardial effusion, pleural effusion, or ascites requiring treatment.
5. Age ≥18 years at the time of enrollment
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. No prior treatment with trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugates (ADC) or ADC containing anti-topoisomerase I agents.
8. At least one target lesion※ identified on contrast-enhanced CT/MRI (head, neck, chest, abdomen, pelvis with ≤5 mm slice thickness) performed within 28 days prior to enrollment (same day of the week is acceptable; this applies similarly to other time-based criteria below) as defined by RECIST 1.1.
9. No administration of anticancer therapies (e.g., chemotherapy, targeted therapy, immunotherapy) within 28 days prior to enrollment.
10. No major surgery under general anesthesia within 28 days prior to enrollment.
11. No radiotherapy (including Gamma Knife or CyberKnife) within 14 days prior to enrollment.
12. Laboratory values within the following criteria based on testing within 14 days prior to enrollment. However, no administration of granulocyte colony-stimulating factor (G-CSF) or blood transfusion within 14 days prior to the blood draw date i) Neutrophil count≧1,500/mm3 ii) Platelet count≧10x104/mm3 iii) Hemoglobin≧9.0 g/dL iv) Albumin≧3.0 g/dL Must meet the specified albumin criterion without receiving albumin supplementation within 72 hours prior to blood sampling.
v) AST≦100 U/L vi) ALT≦100 U/L vii) Total bilirubin≦1.5 mg/dL viii) Creatinine≦1.2 mg/dL Patients with serum creatinine \>1.2 mg/dL are eligible only if Cockcroft-Gault eCCr or 24-hour urine CCr is ≥30 mL/min.
ix) PT-INR ≦1.5
13. Peripheral oxygen saturation (SpO₂) ≥92% on room air within 14 days prior to enrollment.
14. Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or pre-treatment baseline level (except for alopecia and vitiligo). Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible. Participants with Grade ≤2 peripheral neuropathy are eligible.
15. Must not be pregnant or breastfeeding and must meet one of the following conditions:
i) Not of childbearing potential (POCBP; see Appendix 19.2.1) ii) If of childbearing potential:
* Has a negative pregnancy test (high-sensitivity serum or urine β-hCG test) within 14 days before enrollment. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. Additional requirements for pregnancy testing during and after study intervention are in Section 8.2.6.
* Uses 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), as described in Appendix 19.2.2 during the protocol treatment and for at least the time needed to eliminate the study intervention after the last dose of study intervention. The participant agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during this period for the purpose of reproduction. The length of time required to continue contraception for protocol treatment and, with the last administration of the study-drug designated as Day0, until the periods specified below:
Sacituzumab tirumotecan:210 days pembrolizumab: 120 days
* The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive methods for POCBP include the use of condoms, pessaries, oral contraceptives, and intrauterine devices.
* Abstains from breastfeeding during the below period after the last dose of study intervention.
Sacituzumab tirumotecan:10 days pembrolizumab: 120 days Note: Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy.
16. Available to submit tumor tissue specimens for biomarker evaluation, consisting of either archived formalin-fixed, paraffin-embedded (FFPE) tissue blocks or unstained consecutive sections on slides prepared from FFPE block. Whenever possible, tumor tissue obtained from sites of recurrence or metastasis is preferred; however, archival tumor tissue from the primary tumor is acceptable if it was collected recently or is judged to be the most suitable for the study. Refer to the "Specimen Collection, Processing, and Shipping Manual" for detailed procedures.
17. Written informed consent obtained from the patient.
Exclusion Criteria:
1. Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
2. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to \>480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the first dose of study intervention.
3. Received a live or live-attenuated vaccine within 30 days before enrollment. Administration of killed vaccines are allowed.
4. 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 protocol treatment is 2 weeks.
Note: A list of strong inhibitors or inducers of CYP3A4 can be found at the Table 19.3.
Please note that this list is not exhaustive, and investigators should review the locally approved label for all concomitant therapies to ensure they are not strong inducers or inhibitors of CYP3A4.
5. 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.
6. Has received an investigational agent or has used an investigational device within 28 days before enrollment.
7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Note: The following cancers that have been completely resected are not considered exclusionary. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (excluding carcinoma in situ of the bladder).
8. Has severe hypersensitivity (≥Grade 3) to sacituzumab tirumotecan, pembrolizumab and/or any of their excipients or to another biologic therapy.
9. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. ,or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening.
10. Received prior therapy in any setting with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor※ (eg, CTLA-4, OX-40, CD137).
※ The term "agents targeting PD-1, PD-L1, PD-L2, or other coinhibitory T-cell receptors" refers to the following:
* Anti-PD-1 / Anti-PD-L1 / Anti-PD-L2 agents: pembrolizumab; nivolumab; cemiplimab; atezolizumab; avelumab; durvalumab; and similar agents.
* Agents targeting other coinhibitory T-cell receptors: ipilimumab; rocatinlimab; and similar agents.
11. Diagnosis of immunodeficiency or 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 enrollment.
12. Active autoimmune disease that has required systemic treatment in the past 2 years. Or with a history of chronic or recurrent occurrence of the same disease (however, patients with type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, dermatologic disorders not requiring systemic treatment, or conditions expected not to recur in the absence of external triggers will not be excluded).
13. History of stem cell/solid organ transplant.
14. Has an infectious disease requiring systemic treatment.
15. Positive for HBs antigen, or negative for HBs antigen but positive for either HBs antibody or HBc antibody and positive for HBV DNA quantification. Patients are eligible if HBV DNA is below the lower limit of quantification; however, they will be excluded if they have not received at least 4 weeks of antiviral therapy prior to enrollment.
16. Positive for HIV antibody and HCV RNA, or, if HCV RNA is negative, has not completed curative antiviral therapy at least 28 days prior to enrollment. HCV RNA testing is required only for patients who test positive for HCV antibodies.
17. Patients with psychiatric disorders or symptoms that substantially impair daily functioning and who are deemed unsuitable for participation in the study
18. Patients with active gastrointestinal ulcers
19. Has an ongoing or not cured stomatitis
