Background: Ovarian cancer (OC) is characterized by a high recurrence rate following primary surgical and systemic therapy with decreasing efficacy of subsequent treatment lines and accumulating toxicity. Immunotherapy had shown limited efficacy in recurrent OC with 8% response rate in a notable cohort study (Keynote 100).The combination of Pembrolizumab (P) with Lenvatinib (L) was evaluated in a small cohort of platinum resistant OC (LEEP 005) with a 32% response rate. This study assessed the P+L combination’s effectiveness in the platinum sensitive recurrence setting. Methods: In this investigator initiated phase 2 study (NCT04519151), we enrolled patients with platinum sensitive recurrent OC. Inclusion criteria were high grade serous or endometrioid histology, maximum of two previous treatment lines, measurable disease per RECIST 1.1, reserved organ function, and ECOG of 0 or 1. Patients received P (200mg every three weeks) and L (20mg daily) until disease progression or unacceptable toxicity or up to 35 cycles of P. L treatment could be maintained beyond 35 courses of P per investigator decision. Study's primary end point is response rate (RR), and secondary end points encompass progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and quality of life. Correlative study explored archival/fresh tumor tissue and blood biomarkers for response as well as fecal and vaginal microbiome. Results: Between May 2021 and July 2023 24 patients were treated. Median age was 65 years (range 43-77). 11(46%) received 1 prior treatment line and 11(46%) received prior bevacizumab. At a median follow up of 30 months, 12/24 (50%) had RECIST 1.1 response, 2 (8%) with CR and 10 (42%) with PR. Median PFS was 8 months. Median OS and DOR were not reached. At 6 and 12 months, response persisted in 10 and 3 patients, respectively. Treatment-related adverse events were noted in all patients, predominantly hypertension and fatigue. Dose reduction of L occurred in 19 (79%) patients mainly due to hypertension 8(33%), fatigue in 7(30%) and arthralgia in 5(21%). Discontinuation due to adverse event occurred in three patients (hepatitis, nephrotic range proteinuria, diabetic keto-acidosis). There was no treatment-related death. Data on the QOL analysis and biomarker study will be presented later. Conclusions: L+P combination showed meaningful responses and manageable toxicity in platinum sensitive recurrent OC patients thus potentially provides a non chemotherapy alternative. Effect on survival and response to subsequent therapies is yet to be evaluated. Further research is essential to pinpoint the patient subset that can benefit the most from this combination. Clinical trial information: NCT04519151.