Pembrolizumab and Lenvatinib for Platinum- Sensitive Recurrent Ovarian Cancer

Inclusion Criteria:

1. Female participants who are at least 18 years of age on the day of signing informedconsent, with histologically-confirmed diagnosis of EOC (except from low grade tumorsand mucinous histology).
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) OR
4. A WOCBP who agrees to follow the contraceptive during the treatment period andfor at least 120 days after the last dose of study treatment.
5. The participant (or legally acceptable representative if applicable) provides writteninformed consent for the trial.
6. Have measurable disease at baseline based on RECIST 1.1. Lesions
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
8. Have received a front-line platinum-based regimen per local standard of care ortreatment guideline following the primary or interval debunking surgery withradiologically documented disease recurrence no earlier than 6 months followingcompletion of platinum-based therapy. Note: Maintenance treatment following front-line treatment is permitted and countedtogether as part of the front-line treatment. Recurrence is evaluated since lastplatinum-based chemotherapy administration (for patients treated with maintenancebevacizumab or PARP inhibitors) Note: Patients that received maintenance immune checkpointinhibitors will be eligible if progression was documented over 6 months since completion ofthe immunotherapy maintenance treatment. Have received 0 to 1 line of chemotherapy for ROC (or 1 to 2 total prior lines counting thefront line) and must have a PFI (or treatment-free interval) of >6 months for eachtreatment line.
9. Have provided archival tumor tissue sample or newly obtained core or excisional biopsyof a tumor lesion not previously irradiated.
10. Have adequately controlled blood pressure (BP) with or without antihypertensivemedications 10. Have adequate organ function as defined by blood tests.

Exclusion Criteria:

1. A WOCBP who has a positive urine pregnancy test
2. The participant is pregnant or breastfeeding at Screening or Baseline, or is expectingto conceive within the projected duration of the study, starting with the screeningvisit through 120 days after the last dose of trial treatment.
3. The participant has received prior therapy with an anti-PD-1, anti-PD-L1 oranti-PD-L2agent or with an agent directed to another stimulatory or co-inhibitory T-cellreceptor (e.g., CTLA-4, OX-40, CD137) in the last 6 months (6 months are calculatedfrom the last dose until study initiation).
4. The participant has received prior systemic anti-cancer therapy mAb, chemotherapy ortargeted small molecule therapy within 4 weeks prior to the planned first dose of thestudy, including investigational agents within 4 weeks. For tyrosine kinase inhibitors (TKIs), other than lenvatinib, and hormonal therapy a shorter interval of 5 half-livesis allowed between prior therapy and study treatment initiation. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
5. The participant has received prior lenvatinib.
6. The participant has received prior radiotherapy within 2 weeks of start of studytreatment.
7. The patient had prior grade 3 immune related toxicity due to immune checkpointinhibitors or non-infectious pneumonitis.
8. The participant has received more than 2 prior chemotherapy lines.
9. The participant has a history of tumor bleeding one month before study enrollment.
10. The participant has received a live vaccine within 30 days prior to the first dose ofstudy drug.
11. The participant is currently participating in or has participated in a study of aninvestigational agent or has used an investigational device within 4 weeks prior tothe first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational studymay participate as long as it has been 4 weeks after the last dose of the previousinvestigational agent.
12. The participant has a diagnosis of immunodeficiency or is receiving chronic systemicsteroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or anyother form of immunosuppressive therapy within 7 days prior to the first dose of studydrug. Note: The use of physiologic doses of corticosteroids is allowed.
13. The participant has a known active second/additional malignancy that is progressing orhas required active treatment within the past 5 years Note: Exceptions include basalcell carcinoma of the skin, squamous cell carcinoma of the skin that has undergonepotentially curative therapy, in situ cervical cancer.
14. The participant has a known active CNS metastases and/or carcinomatous meningitis. Note: Participants with previously treated brain metastases may participate providedthey are radiologically stable, i.e., without evidence of progression for at least 4weeks by repeat imaging (note that the repeat imaging should be performed during studyscreening), clinically stable and without requirement of steroid treatment for atleast 14 days prior to first dose of study treatment.
15. The participant has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any ofexcipients.
16. The participant has an active autoimmune disease that has required systemic treatmentin the past 2 years (i.e. with use of disease modifying agents, corticosteroids orimmunosuppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroidreplacement therapy for adrenal or pituitary insufficiency, etc.) is not considered aform of systemic treatment.
17. The participant has an active infection requiring systemic therapy.
18. The participant has a known history of human immunodeficiency virus (HIV 1/2antibodies).
19. The participant has a known history of hepatitis B or known active hepatitis C virus
20. The participant has a history or current evidence of any condition, therapy, orlaboratory abnormality that might confound the results of the study, interfere withthe subject's participation for the full duration of the study, or is not in the bestinterest of the subject to participate, in the opinion of the treating investigator.
21. The participant has known psychiatric or substance abuse disorders that wouldinterfere with cooperation with the requirements of the trial.
22. The participant has had an active allogenic tissue/solid organ transplant.
23. The participant has uncontrolled blood pressure
24. The participant has clinically significant electrolyte abnormalities that have notbeen corrected.
25. The participant has significant cardiovascular impairment: history of congestive heartfailure greater than New York Heart Association (NYHA) Class II, unstable angina,myocardial infarction or cerebrovascular accident (CVA) within 6 months of the firstdose of study drug, or cardiac arrhythmia associated with hemodynamic instabilityrequiring medical treatment at Screening.
26. The participant has bleeding or thrombotic disorders, radiographic evidence of majorblood vessel invasion/infiltration, or is at risk for severe hemorrhage. Note: The degree of tumor invasion/infiltration of major blood vessels (e.g. carotidartery) should be considered because of the potential risk of severe hemorrhageassociated with tumor shrinkage/necrosis following lenvatinib therapy.
27. The participant has >1+ proteinuria on urine dipstick testing unless a 24-hour urinecollection for quantitative assessment indicates that the urine protein is <1 g/24hours.
28. Prolongation of QTc interval to >480 ms.
29. Left ventricular ejection fraction (LVEF) below the institutional normal range asdetermined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
30. The participant has gastrointestinal malabsorption, gastrointestinal anastomosis, orany other condition that might affect the absorption of lenvatinib.
31. The participant has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinalfistula.
32. The participant has a known intolerance to the study treatment (or any of itsexcipients).