A phase II trial of dostarlimab and niraparib combination therapy in patients with stage III-IV recurrent or refractory penile cancer.

TPS14 Background: Penile squamous cell carcinoma (PSCC) is a rare and aggressive malignancy with limited therapeutic options, particularly for patients whose disease progresses despite platinum-based chemotherapy. The overall survival rate for these patients is less than five months with standard treatment, highlighting the critical need for new and effective therapies. Preclinical studies have demonstrated a synergistic effect between PARP inhibitors and immune checkpoint inhibitors in PSCC animal models. The combination of niraparib and dostarlimab holds promise in eliciting a robust antitumor immune response in patients with cisplatin-refractory PSCC. Methods: This is an open-label, multi-center, phase II study employing a Simon two-stage design to assess the efficacy and safety of niraparib and dostarlimab in patients with advanced relapsed or refractory PSCC. Patients must provide an adequate tumor tissue sample at screening for molecular and immune profiling. Blood samples are collected at cycle 1, day 1 (C1D1) for exploratory molecular analysis, at cycle 3, day 1 (C3D1), at the time of investigator-assessed partial response (PR) or complete response (CR), and at the end-of-treatment visit. Niraparib will be administered orally at a dose of 200 mg once daily from day 1 to day 21 of each cycle, continuing until disease progression or unacceptable toxicity. Dostarlimab will be administered intravenously once every three weeks for cycles 1 through 4 and then every six weeks thereafter. Eligible patients must have histologically confirmed stage III (unresectable) or stage IV penile cancer as defined by the American Joint Committee on Cancer (AJCC) staging system. They must have experienced disease progression or intolerance after one line of platinum-based therapy, possess a life expectancy of at least 12 weeks, and have an ECOG performance status (PS) of 0 or 1 (patients with an ECOG PS of 2 may be included upon discussion with the principal investigator). Additional eligibility criteria include measurable disease according to the Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST), adequate organ function, and no prior treatment with immunotherapy agents, cancer vaccines, adoptive cell therapies, or cytokine therapies. The primary efficacy endpoint is the investigator-assessed confirmed overall response rate (ORR), with tumor response evaluated according to iRECIST criteria. Patients who receive at least one complete dose of either study drug will be considered evaluable for response. Secondary endpoints include progression-free survival (PFS), overall survival (OS), and duration of response (DOR), safety, and tolerability. Enrollment began in December 2022, and 14 of the planned 25 patients have been enrolled. Clinical trial information: NCT05526989 .