Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032.

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Session Type and Session Title: 
Oral Abstract Session, Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 7503)
Scott Joseph Antonia, Johanna C. Bendell, Matthew Hiram Taylor, Emiliano Calvo, Dirk Jaeger, Filippo G. De Braud, Patrick Alexander Ott, M. Catherine Pietanza, Leora Horn, Dung T. Le, Michael Morse, Jose A. Lopez-Martin, Paolo Antonio Ascierto, Olaf Christensen, Joseph Grosso, Jason S. Simon, Chen-Sheng Lin, Joseph Paul Eder; Moffitt Cancer Center, Tampa, FL; Sarah Cannon Research Institute, Nashville, TN; Oregon Health and Science University, Portland, OR; START Madrid, Centro Integral Oncológico Clara Campal, Madrid, Spain; National Center for Tumor Diseases, University Hospitals Heidelberg, Heidelberg, Germany; Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Dana-Farber Cancer Institute, Boston, MA; Memorial Sloan Kettering Cancer Center, New York, NY; Vanderbilt-Ingram Cancer Center, Nashville, TN; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Duke University Medical Center, Durham, NC; Hospital 12 de Octubre, Madrid, Spain; Istituto Nazionale Tumori IRCCS, Naples, Italy; Bristol-Myers Squibb, Princeton, NJ; Bristol-Myers Squibb Company, Princeton, NJ; Yale Cancer Center, Yale School of Medicine, New Haven, CT

Abstract Disclosures


Background: Patients (pts) with SCLC respond to initial platinum (PLT) based chemotherapy (CT), but rapidly progress. Combined blockade of PD-1 and CTLA-4 immune checkpoint pathways has anti-tumor activity with a manageable safety profile. Nivolumab (NIVO) is a fully human IgG4 PD-1 immune checkpoint inhibitor approved in the US & Japan. Interim safety and efficacy of NIVO +\- ipilimumab (IPI), a CTLA-4 checkpoint inhibitor, in pretreated SCLC pts are reported. Methods: Pts who were PLT sensitive or refractory and had progressive disease were enrolled regardless of tumor PD-L1 status or number of prior CT regimens. This open-label study randomized pts to NIVO 3 mg/kg IV Q2W or NIVO+IPI (1 + 1 mg/kg, 1 + 3 mg/kg or 3 + 1 mg/kg) IV Q3W for 4 cycles followed by NIVO 3 mg/kg Q2W. Primary objective was overall response rate (ORR). Other objectives were safety, PFS, OS and biomarker analysis. Results: Seventy-five pts were enrolled (NIVO, n = 40; NIVO+IPI, n = 35); 59% had ≥ 2 prior regimens. Drug-related adverse events (DrAEs) in ≥ 10% were fatigue (18%), diarrhea (13%), nausea (10%), and decreased appetite (10%) with NIVO; and fatigue (29%), diarrhea (17%), pruritus (14%), nausea, endocrine disorders and rash (11% each) with NIVO+IPI. Gr 3/4 DrAE in ≥ 5% included diarrhea and rash (6% each; NIVO+IPI). Drug-related pneumonitis occurred in 2 pts (1 per arm). One pt experienced a drug-related SAE of myasthenia gravis on study which was fatal. Of 40 evaluable NIVO pts, partial response (PR) was seen in 6, 15% (duration of ongoing responses [DOR] 80-251+ days); stable disease (SD) in 9, 22.5%; and progressive disease (PD) in 25, 62.5%. In 20 evaluable NIVO+IPI pts, 1 had complete response (CR), 5% (DOR 322+ days); 4 had a PR, 20% (DOR 41-83+ days); 6 had SD, 30%, and 9 had PD, 45%. In the NIVO+IPI arm, 12 pts had not reached first tumor assessment and 3 were not evaluable. Nine pts (23%) continue treatment with NIVO and 19 (54%) with NIVO+IPI. Conclusions: In this PD-L1 unselected SCLC population with progression post-PLT, NIVO alone or combined with IPI was tolerable. ORR was 15% (NIVO) and 25% (NIVO+IPI) for evaluable pts; durable responses were noted. Updated safety, clinical activity and biomarker analysis will be presented. Clinical trial information: NCT1928394