B70: Phase 1/2 study of nivolumab (NIVO) with or without ipilimumab (IPI) for treatment of recurrent small cell lung cancer (SCLC): CA209-032
1START Madrid, Madrid, Spain,2H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA,3Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN, USA,4Oregon Health & Science University, Portland, OR, USA,5Heidelberg University Hospital, Heidelberg, Germany,6Istituto Nazionale dei Tumori, Milan, Italy,7Dana-Farber Cancer Institute, Boston, MA, USA,8Memorial Sloan Kettering Cancer Center, New York, NY, USA,9Vanderbilt-Ingram Cancer Center, Nashville, TN, USA,10The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA,11Duke University Medical Center, Durham, NC, USA,12Hospital Universitario 12 de Octubre, Madrid, Spain,13Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy,14Bristol-Myers Squibb, Princeton, NJ, USA,15Yale Comprehensive Cancer Center, New Haven, CT, USA
Patients with SCLC respond to initial platinum-based chemotherapy, but rapidly progress. Combined blockade of PD-1 and CTLA-4 immune checkpoint pathways has anti-tumor activity with a manageable safety profile. NIVO is a fully human IgG4 PD-1 inhibitor approved in the US & Japan. This open-label study reported interim safety and efficacy of NIVO±IPI, a CTLA-4 inhibitor, in pretreated SCLC patients.
Platinum-sensitive or refractory patients with progressive disease were enrolled regardless of tumor PD-L1 status or number of prior chemotherapy regimens. Patients were randomized: NIVO 3mg/kg IV Q2W or NIVO+IPI (1+1mg/kg, 1+3mg/kg, 3+1mg/kg) IV Q3W for 4 cycles, then NIVO 3mg/kg Q2W. Primary objective was overall response rate (ORR). Other objectives were safety, PFS, OS, and biomarker analysis.
Of 75 patients enrolled (NIVO, n=40; NIVO+IPI, n=35); 59% had ?2 prior regimens. Treatment-related adverse events (TRAEs) 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. Grade 34 TRAEs in ?5% included diarrhea and rash (6% each; NIVO+IPI). Drug-related pneumonitis occurred in 2 patients (1/arm). One patient experienced a fatal TRAE of myasthenia gravis.
In 40 evaluable NIVO patients, 15% experienced partial response (PR; duration of ongoing response [DOR] 80251+days); 22.5% stable disease (SD); and 62.5% progressive disease (PD). In 20 evaluable NIVO+IPI patients, 5% experienced complete response (CR; DOR 322+days); 20% PR (DOR 4183+days); 30% SD, and 45% PD. Twelve NIVO+IPI patients did not reach first tumor assessment and 3 were non-evaluable. Nine patients continue NIVO treatment and 19 continue NIVO+IPI.
NIVO or NIVO+IPI were tolerable in this population. ORR for evaluable patients was 15% (NIVO) and 25% (NIVO+IPI); durable responses were noted. Updated safety, clinical activity and biomarker analysis will be presented.