Background: The peritoneal cavity is a frequent site of metastasis and recurrence for gynecologic malignancy, including approximately 80% of epithelial ovarian cancer (EOC) that presents with peritoneal involvement. These observations have led to the use of intraperitoneal (IP) route of administration for traditional cytotoxic chemotherapy. IP immunotherapy is a recognized but under explored area of clinical investigation with many potential advantages. Indeed, IP administered antibodies in both animals and human subjects are associated with absent or much lower peripheral blood concentrations. In addition to higher local and lower systemic exposure, other theoretical advantages include preferential binding to intraperitoneal and intratumoral immune cells, and absorption through the draining lymphatics of the peritoneal cavity. These pelvic and peri-aortic lymph nodes represent the most relevant lymphoid organs and as such may be the ideal site for T cell activation and trafficking back to the peritoneal tumor. Methods: The trial (NCT03508570) is a single-institution phase Ib trial to determine the recommended phase II dosing (RP2D) of IP administration of nivolumab in combination with ipilimumab. For the purpose of dose finding, the assessment period for dose limiting toxicity (DLT) is 12 weeks. The trial starts with a safety lead-in to confirm the safety of IP nivolumab before combining it with ipilimumab. A maximum sample size of 12 will be used to find the RP2D for nivolumab, up to 24 patients for the combination, and a planned expansion will be carried out such that at least 12 EOC patients are treated at RP2D of the intraperitoneal combination strategy. The secondary objectives are to describe the pharmacokinetics and toxicities, and to estimate the clinical benefit rate for the expansion cohort. Translational objectives include description of immunologic and biologic changes in serial blood and IP fluid collections as well as pre and on-treatment biopsies. Eligibility criteria include recurrent or progressive biopsy-confirmed platinum resistant EOC or other gynecologic cancer with measurable peritoneal disease, and no exposure to prior treatment with checkpoint inhibition. Enrollment began in January of 2019 with 3 subjects enrolled to date. Accrual update will be provided at the annual meeting. Clinical trial information: NCT03508570