Scott Antonia¹, Johanna Bendell²,Matthew Taylor³, Emiliano Calvo⁴, Dirk Jäger⁵, Filippo De braud⁶, Patricka. Ott⁷, M. catherine Pietanza⁸, Leora Horn⁹, Dung t. Le¹⁰, Michaela. Morse¹¹, José a. López-martin¹², Paolo a. Ascierto¹³, Olaf Christensen¹⁴, Josephf. Grosso¹⁴, Jason Simon¹⁴, Chen-sheng Lin¹⁴, Joseph paul Eder¹⁵

¹Thoracic OncologyDepartment, H. Lee Moffitt Cancer Center & Research Institute, ²PLLC, Sarah CannonResearch Institute/Tennessee Oncology, ³Oregon Health &Science University, ⁴Centro IntegralOncológico Clara Campa, START Madrid, ⁵Heidelberg UniversityHospital, ⁶Istituto Nazionale deiTumori, ⁷Dana-Farber CancerInstitute, ⁸Memorial Sloan KetteringCancer Center, ⁹Vanderbilt-Ingram CancerCenter, ¹⁰The Sidney KimmelComprehensive Cancer Center at Johns Hopkins, ¹¹Duke University MedicalCenter, ¹²‘12 de Octubre’University Hospital and Research Institute, ¹³Istituto NazionaleTumori Fondazione Pascale, ¹⁴Bristol-MyersSquibb, ¹⁵Yale Cancer Center

Objective:Patients (pts) with SCLC respond toinitial platinum (PLT) based chemotherapy (CT), but rapidly progress. Combinedblockade of programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen-4(CTLA-4) immune checkpoint pathways has anti-tumor activity with a manageablesafety profile. Nivolumab (nivo) is a fully human IgG4 PD-1 immune checkpointinhibitor approved in the EU, US, & Japan. Interim efficacy and safety ofnivo +/- ipilimumab (ipi), a CTLA-4 checkpoint inhibitor, in pretreated SCLCpts are reported. 

Method: PLT sensitive or refractory pts withprogressive disease (PD) were enrolled regardless of tumor PD-L1 status ornumber of prior CT treatments (tx), and randomized to nivo 3mg/kg IV Q2W ornivo+ipi (1+1mg/kg or 1+3mg/kg) IV Q3W for 4 cycles followed by nivo 3mg/kgQ2W. Primary objective was ORR. Other objectives were safety, PFS, OS, andbiomarker analysis. 

Result: Of 90 pts enrolled (nivo, n=40; nivo+ipi,n=50 [nivo1+ipi1, n=3; nivo1+ipi3, n=47]); 53% had ≥2 prior tx.Treatment-related adverse events (TRAEs) in ≥10% were fatigue (18%), diarrhea(13%), nausea (10%), and decreased appetite (10%) with nivo; diarrhea (23%),fatigue (21%), rash (21%), pruritus (19%), hypothyroidism (15%), nausea,hyperthyroidism and maculopapular rash (13% each), and increased lipase (11%)with nivo1+ipi3. Grade 3–4 TRAEs in ≥5% included diarrhea (9%) and increasedlipase (6%) with nivo1+ipi3. Pneumonitis occurred in 2 pts in nivo (grade 1–2)and 1 pt in nivo1+ipi3 (grade 3–4). One pt in the nivo1+ipi 3 arm experiencedfatal myasthenia gravis. Of 40 evaluable nivo pts, 18% experienced PR (medianduration of ongoing responses [mDOR] not reached [range 4.1–11+ mo]); 20% SD;and 53% PD. Of 46 evaluable nivo+ipi pts, 2% experienced CR; 15% PR (mDOR 6.9mo [range 1.5–11.1+ mo]); 37% SD, and 37% PD. Seven pts in the nivo+ipi armexperienced PR after database lock; 4 pts in the nivo+ipi arm did not reachfirst tumor assessment. 20% pts continue treatment with nivo and 42% withnivo+ipi. 

Conclusion: In a PD-L1-unselected SCLC population withprogression post PLT-CT, nivo or nivo+ipi was tolerable. ORR was 18% (nivo) and17% (nivo+ipi); durable responses were noted. Updated safety, clinicalactivity, and biomarker analysis will be presented.Clinical Trial Number:NCT1928394.

Key Words: nivolumab  ipilimumab small cell lung cancer