Assessment of the Efficacy and Safety of Pembrolizumab for Ovarian Squamous Cell Carcinoma

This study includes female patients 18 years of age or older with advanced or recurrent unresectable squamous cell carcinoma of the ovary. No prior approval (e.g., waiver or exemption) is granted for deviations from the study protocol regarding inclusion criteria.

Inclusion Criteria:

• Participants are eligible to be included in the study only if all of the followingcriteria apply:

1. Female participants who are at least 18 years of age on the day of signinginformed consent.

2. A female participant is eligible to participate if she is not pregnant, notbreastfeeding, and at least one of the following conditions applies:

3. Not a woman of childbearing potential (WOCBP) as defined OR

4. A WOCBP who agrees to follow the contraceptive guidance during thetreatment period and for at least 120 days after the last dose of studytreatment.

5. The participant is diagnosed with advanced or recurrent unresectable squamouscell carcinoma of ovary which are histologically confirmed.

6. The participant provides written informed consent for the trial.

7. Have measurable disease based on RECIST 1.1. Lesions situated in a previouslyirradiated area are considered measurable if progression has been demonstratedin such lesions.

8. Archival tumor tissue sample or newly obtained [core, incisional or excisional]biopsy of a tumor lesion not previously irradiated has been provided.Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.Newly obtained biopsies are preferred to archived tissue.

9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.Evaluation of ECOG is to be performed within 7 days prior to the first dose ofstudy intervention.

10. Have adequate organ function as defined in the following. Specimens must becollected within 28 days prior to the start of study intervention.

• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100 000/µL
• Hemoglobin ≥9.0 g/dL
• Creatinine ≤1.5 × upper limit of normal (ULN) OR Measured or calculatedbcreatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULNof Creatinine
• Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants withtotal bilirubin levels >1.5 × ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 ×ULN (≤5 × ULN for participants with liver metastases)
• PT - International normalized ratio (INR) < 1.5
• Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participantis receiving anticoagulant therapy as long as PT or aPTT is withintherapeutic range of intended use of anticoagulants

9.1 Hepatitis B positive subjects

• Participants who are HBsAg positive are eligible if they have received Hepatitis Bvirus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viralload prior to randomization.

• Participants should remain on anti-viral therapy throughout study intervention andfollow local guidelines for HBV anti-viral therapy post completion of studyintervention.

9.2 Hepatitis C positive subjects

• Participants with history of Hepatitis C virus (HCV) infection are eligible if HCVviral load is undetectable at screening.

• Participants must have completed curative anti-viral therapy at least 4 weeks priorto randomization.

Exclusion Criteria:

• Participants are excluded from the study if any of the following criteria apply:

1. A WOCBP who has a positive serum or urine pregnancy test within 72 hours priorto registration .

2. TMB-High (TMB score ≥ 10 mut/Mb) by FoundationOne CDx Cancer Genome Profile.

3. MSI-High by microsatellite instability test or FoundationOne CDx Cancer GenomeProfile.

4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agentor with an agent directed to another stimulatory or co-inhibitory T-cellreceptor (eg, CTLA-4, OX 40, CD137).

5. Has received prior systemic anti-cancer therapy including investigationalagents within 28 days prior to registration.Note: There is no limit to the number of chemotherapy treatments prior to thestudy. Participants must have recovered from all adverse events (AE) due toprevious therapies to ≤Grade 1 or baseline. Participants with alopecia and ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEGrade ≤2 requiring treatment or hormone replacement may be eligible Note: Ifthe participant had major surgery, the participant must have recoveredadequately from the procedure and/or any complications from the surgery priorto starting study intervention.

6. Has received prior radiotherapy within 2 weeks of start of study intervention.Participants must have recovered from all radiation-related toxicities, notrequire corticosteroids, and not have had radiation pneumonitis. A 1-weekwashout is permitted for palliative radiation (≤2 weeks of radiotherapy) tonon-central nervous system (CNS) disease.

7. Has received a live vaccine or live-attenuated vaccine within 30 days beforethe first dose of study intervention. Administration of killed vaccines isallowed.Note: please refer to Section 5.4.2 for information on COVID-19 vaccines

8. Is currently participating in or has participated in a study of aninvestigational agent or has used an investigational device within 4 weeksprior to the first dose of study intervention.Note: Participants who have entered the follow-up phase of an investigationalstudy may participate as long as it has been 4 weeks after the last dose of theprevious investigational agent.

9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroidtherapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any otherform of immunosuppressive therapy within 7 days prior to the first dose ofstudy drug.

10. Known additional malignancy that is progressing or has required activetreatment within the past 2 years. Note: Participants with basal cell carcinomaof the skin, squamous cell carcinoma of the skin or carcinoma in situ,excluding carcinoma in situ of the bladder, that have undergone potentiallycurative therapy are not excluded.

11. Has known active CNS metastases and/or carcinomatous meningitis. Participantswith previously treated brain metastases may participate provided they areradiologically stable, i.e. without evidence of progression for at least 4weeks by repeat imaging (note that the repeat imaging should be performedduring study screening), clinically stable and without requirement of steroidtreatment for at least 14 days prior to first dose of study intervention.

12. Has severe hypersensitivity (≥Grade 3) to MK-3475 and/or any of its excipients.

13. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids orimmunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency, etc.) is not considered a form of systemic treatment and isallowed.

14. Has a history of (non-infectious) pneumonitis/interstitial lung disease thatrequired steroids or has current pneumonitis/interstitial lung disease.

15. Has an active infection requiring systemic therapy.

16. Has a known history of Human Immunodeficiency Virus (HIV) infection.

17. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBVDNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCVRNA) infection.

18. Has a history or current evidence of any condition, therapy, or laboratoryabnormality or other circumstance that might confound the results of the study,interfere with the participant's participation for the full duration of thestudy, such that it is not in the best interest of the participant toparticipate, in the opinion of the treating investigator.

19. Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

20. Is pregnant or breast feeding, or expecting to conceive or father childrenwithin the projected duration of the study, starting with the screening visitthrough 120 days after the last dose of trial treatment.

21. Has had an allogenic tissue/solid organ transplant.