A phase II clinical trial of cpi-613 in patients with relapsed or refractory small cell lung carcinoma

Abstract

Backgroun Small cell lung cancer (SCLC) is a common lung cancer which presents with extensiv stage disease at time of diagnosis in two-Thirds of patients. For treatment of advanced disease traditional platinum doublet chemotherapy induces response rates up to 80% bu with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibit the altered form of mitochondrial energy metabolism in tumor cells Method We evaluated CPI-613 with a single-Arm, open-label phase II study in patients wit relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and of weeks 1-3 of 4 week cycle. The primary outcome was response rate as assessed by C imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free surviva (PFS), overall survival (OS), and toxicity. Twelve patients were accrued (median age 57yo who had previously received between 1 and 4 lines of chemotherapy (median 1) for SCL with a treatment-free interval of less than 60 days in 9 of the 12 patients Result No complete or partial responses were seen. Ten patients (83%) progressed as bes response and 2 (17%) were not evaluable for response. Median time to progression wa 1.7 months (range 0.7 to 1.8 months). Eleven patients (92%) died with median overall surviva of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack o efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequentl treated with standard topotecan then demonstrated treatment response with surviva for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synerg in-vitro for CPI-613 with topotecan Conclusion Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combinatio with a topoisomerase inhibitor is warranted.