Pembrolizumab and lenvatinib in the treatment of recurrent, platinum-resistant ovarian carcinoma: A single institution experience.

e17612 Background: Advanced stage ovarian carcinoma has a poor prognosis with recurrence rates of more than 80% and a 5-year survival of approximately 36-45%. The response of platinum resistant disease to standard therapy is limited and generally of short duration. Pembrolizumab and lenvatinib are FDA approved for treatment of microsatellite stable (MSS)/mismatch repair proficient (pMMR) endometrial and renal cell cancers. Early phase II studies have also shown promising treatment results in a variety of other advanced solid tumors, including MSS/pMMR ovarian cancer. We report on the clinical outcome of recurrent MSS/pMMR ovarian cancer patients at our institution treated with this therapy. Methods: For this retrospective cohort study, all patients with a diagnosis of ovarian cancer treated with pembrolizumab and lenvatinib from January 2020 to April 2024 at MD Anderson Cancer Center at Cooper, Camden, NJ were included in the analysis. Demographic data, tumor characteristics, germline/somatic genetic testing, and treatment duration were collected. Response rate by RECIST criteria and progression free survival (PFS) were calculated. Results: A total of 16 patients were identified. Most patients had high-grade serous (n=11, 68.75%) or clear cell histology (n=4, 25%) with an initial diagnosis of FIGO stage III/IV disease (n=15, 93.75%). Eighty-one percent of patients had platinum resistant recurrent disease. The median number of prior lines of therapy was 3. Of the patients who underwent next generation sequencing (n=11), all were MSS with low tumor mutational burden (TMB). Three patients discontinued therapy after one cycle, unrelated to drug toxicity, and were non-evaluable for response. Of the 13 patients evaluable for response, 54% (n=7) had a partial response and 31% (n=4) had stable disease, for a clinical benefit rate of 85%. All three evaluable patients with clear cell histology exhibited a partial response. The median PFS for all evaluable patients was 7.9 months (1.8-17.8 months). The most common toxicities were gastrointestinal such as nausea, vomiting, and diarrhea. Three patients experienced grade 3 diarrhea and one patient experienced grade 3 renal toxicity requiring a dose reduction of lenvatinib and/or treatment interruption of both agents. It should be noted that the patient with renal toxicity had baseline renal dysfunction prior to treatment initiation. At the time of data analysis, 2 patients remained on treatment. Conclusions: Pembrolizumab-lenvatinib therapy demonstrated favorable clinical benefit and manageable toxicities in patients with recurrent, largely platinum resistant MSS/pMMR ovarian cancer; a group of patients in need of more therapeutic options.