Phase II Study of Combination Rucaparib With Nivolumab in Platinum-Sensitive Small Cell Lung Carcinoma Patients as Maintenance After Induction Therapy With Platinum Doublet

Small cell lung cancer (SCLC) is one of the most aggressive malignancies with a 5-year survival rate of less than 7%. SCLC is characterized by rapid doubling time, high growth fraction and early development of widespread metastases. SCLC accounts for roughly 93% of all high-grade neuroendocrine carcinomas. The prognosis for SCLC is extremely poor with a median survival less than a year for extensive-stage disease. Therapeutic options have not advanced significantly in over two decades, with frontline treatment consisting of platinum doublet therapy for 3-6 cycles. While most patients show an initial favorable response to Carboplatin/cisplatin + etoposide, this response is usually short-lived. Most patients relapse with resistant disease between 3 to 6 months after completion of initial chemotherapy.

Based on preclinical data supporting the role of immune checkpoint and PARP (poly ADP ribose polymerase ) inhibitors in SCLC, combining nivolumab and rucaparib has the potential to prolong progression-free survival and overall survival. These two classes of drugs have non-overlapping toxicities. This novel combination has not been tried in a front-line maintenance setting for SCLC.

Eligible patients will have pathological (biopsy) or cytologically confirmed stage IV SCLC, and have achieved either partial or complete response post frontline chemotherapy with platinum doublet. Patients will be treated with combination rucaparib and nivolumab. The recommended starting dose of rucaparib as a continuously administered oral monotherapy is 600 mg BID. Nivolumab will be administered as an intravenous infusion once every 4 weeks at a fixed dose of 480 mg. In the absence of treatment delays due to adverse event(s), treatment may continue for 24 months.

Progression-free survival, overall survival, disease control rates, objective response rate, quality of life, and tumor mutation burden will be evaluated during this study (up to 2 years).