A phase 2 study of the combination dostarlimab with niraparib in patients with penile carcinoma that has progressed following chemotherapy.
Authors: Neubauer Robin , Pettaway Curtis Alvin , Spiess Philippe E. , Jain Rohit K. , Chadha Juskaran , Zhang Jingsong , Chahoud Jad , Roman Souza Gabriel , Dhillon Jasreman , Moscu Anay , Janeway Ryan , Harris David Walter , Lu Xin , Jameel Ghazal , Raymond Sarah , Oschmann Erika , Kim Youngchul , Campbell Matthew T , Schuckman Anne K. 
Published: January 2024

TPS13

Background: Penile squamous cell carcinoma (PSCC) is a rare and deadly cancer, with limited therapy options in patients with disease progressive on platinum chemotherapy. Patients are encouraged to enroll in clinical trials since the overall survival is less than 5 months with standard therapy. Development of efficacious treatment options for patients with chemotherapy refractory PSCC, remains an unmet need. Preclinical work suggests synergic activity between PARP inhibitors and immune checkpoint inhibitors in PSCC animal models. The niraparib plus dostarlimab combination may generate a robust antitumor immune response in cisplatin refractory patients with PSCC. Methods: This is an open-label, multi-center, Simon 2 stage design, phase 2 study to evaluate the efficacy and safety of the combination of niraparib and dostarlimab in patients with advanced relapsed/refractory PSCC. Patients must provide a sufficient tumor tissue sample for molecular and immune testing at screening. Blood samples will be collected at C1D1 for exploratory molecular testing, at C3D1 and at the time of investigator-assessed partial response (PR) or complete response (CR), and at the end of treatment visit. Niraparib at 200 mg daily will be administered orally once daily on days 1 to 21 and dostarlimab intravenously once every three weeks for cycles 1 to 4 and once every 6 weeks thereafter. Niraparib will be administered at 200 mg, oral, once daily, from days 1 through 21 until progression of disease or toxicity. Eligible patients must have histologically confirmed stage III (unresectable) or stage IV penile cancer according to the American Joint Committee on Cancer (AJCC) staging system, have had progression of disease or poor tolerance to one line of platinum therapy, have a life expectancy of more than 12 weeks, have an ECOG PS of 0 or 1 (ECOG PS 2 can be included after discussion with PI), measurable disease per Immune-Modified Response Evaluation Criteria in Solid Tumors iRECIST, adequate organ function, and must not have received any prior immuno-oncology regimens, cancer vaccines, adoptive cell therapies, or other cytokine therapies. The primary efficacy endpoint is Investigator-assessed confirmed overall response rate (ORR). Tumor response will be evaluated using iRECIST. Patients who receive at least 1 complete dose of either study drug will be considered evaluable for response. The secondary endpoints are to estimate the progression free survival (PFS) overall survival measured duration of Response (DOR) and to evaluate the safety and tolerability of the niraparib and dostarlimab combination in patients with PSCC. Six patients of the 25-patient target enrollment have been enrolled. Clinical trial information: NCT05526989 .