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Background: Small cell lung cancer SCLC is a common lung cancer hich presents ith extensive stage disease at time of diagnosis in to-thirds of patients. For treatment of advanced disease, traditional platinum doublet chemotherapy induces response rates up to 80 percent but ith fe durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibits the altered form of mitochondrial energy metabolism in tumor cells. Methods: We evaluated CPI-613 ith a single-arm, open-label phase II study in patients ith relapsed or refractory SCLC. CPI-613 as given at a dose of 3,000 mgm2 on days 1 and 4 of eeks 1-3 of 4 eek cycle. To cycles ere given to complete a treatment course prior to re-evaluation. The primary outcome as response rate as assessed by CT imaging using RECIST v1.1 criteria. Secondary outcomes ere progression-free survival PFS , overall survival OS , and toxicity. Telve patients ere accrued median age 57yo ho had previously received beteen 1 and 4 lines of chemotherapy median 1 for SCLC ith a treatment-free interval of less than 60 days in 9 of the 12 patients. They received a total of 16.3 cycles median 1.63 of therapy ith a median maximum CPI-613 dosage of 30,000 mgm2 range 9,000 to 36,000 . Results: No complete or partial responses ere seen. Ten patients 83 percent progressed as best response and 2 17 percent ere not evaluable for response. Median time to progression as 1.7 months range 0.7 to 1.8 months . Eleven patients 92 percent died ith median overall survival of 4.3 months range 1.2 to 18.2 months . The study as closed early due to lack of efficacy. Of note, three out of three patients ho progressed after CPI-613 and ere subsequently treated ith standard topotecan then demonstrated treatment response ith survival for 18.2,7.4, and 5.1 months. We conducted laboratory studies hich found synergy in-vitro for CPI-613 ith topotecan. Conclusions: Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combination ith a topoisomerase inhibitor is arranted. Clinical trial information: lta href=http:clinicaltrials.govshoNCT01931787 NCT01931787,J Clin Oncol 34, 2016 suppl; abstr e20100 ,NCT01931787Publication Only Lung CancerNon-Small Cell Local-RegionalSmall CellOther Thoracic Cancers
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