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  • Open Access

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

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Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P376

  • Published:


  • Small Cell Lung Cancer
  • Ipilimumab
  • Immune Checkpoint
  • Checkpoint Inhibitor
  • Immune Checkpoint Inhibitor


Treatment options for SCLC after failing platinum-based (PLT) chemotherapy (CT) are limited. Combined blockade of programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) immune checkpoint pathways has anti-tumor activity with a manageable safety profile. Nivolumab is a fully human IgG4 PD-1 immune checkpoint inhibitor approved for melanoma and squamous NSCLC in the US and for melanoma in the EU and Japan. Interim efficacy and safety of nivolumab +/- ipilimumab, a CTLA-4 checkpoint inhibitor, in pretreated SCLC patients are reported.


Patients with progressive disease (PD) after PLT first-line treatment were eligible, regardless of platinum sensitivity, tumor PD-L1 expression, or number of prior CT regimens. Patients were randomized to nivolumab 3 mg/kg IV Q2W or nivolumab+ipilimumab (1+1 mg/kg or 1+3 mg/kg) IV Q3W for 4 cycles, followed by nivolumab 3 mg/kg Q2W. Primary objective was objective response rate (ORR). Additional objectives included safety, progression-free survival (PFS), overall survival (OS), and biomarker analysis.


Of 90 patients enrolled (nivolumab, n=40; nivolumab+ipilimumab, n=50 [nivolumab 1+ipilimumab 1, n=3; nivolumab 1+ipilimumab 3, n=47]), 53% had ≥2 prior regimens. Efficacy results for evaluable patients are shown (Table 1). 20% of patients in the nivolumab arm and 42% in the nivolumab+ipilimumab arms remain on treatment. Discontinuations due to treatment-related adverse events (TRAEs) occurred in 8% of nivolumab and 11% of nivolumab+ipilimumab patients. TRAEs (all grades) in ≥10% of patients included fatigue (18%), diarrhea (13%), nausea (10%), and decreased appetite (10%) with nivolumab; and diarrhea (23%), fatigue (21%), rash (21%), pruritus (19%), hypothyroidism (15%), hyperthyroidism (13%), nausea (13%), maculopapular rash (13%), and increased lipase (11%) with nivolumab 1+ipilimumab 3. Grade 3–4 TRAEs in ≥5% of patients occurred only in the nivolumab 1+ipilimumab 3 arm and included diarrhea (9%) and increased lipase (6%). Pneumonitis occurred in 2 patients in the nivolumab arm (grade 1–2) and 1 patient in the nivolumab 1+ipilimumab 3 arm (grade 3–4). One patient in the nivolumab 1+ipilimumab 3 arm had treatment-related myasthenia gravis with fatal outcome. Updated efficacy, safety, biomarker analysis, and case studies (responses in a patient with PLT-refractory disease and in a patient after crossover to nivolumab/ipilimumab) will be presented.

Table 1


Nivolumab (n-40)

Nivolumab + Ipilimumab (n=46)a

ORR, %



 Complete response, %



 Partial response, %



 Stable disease,b %



 Disease control rate, %



 Progressive disease, %



Death prior to first response assessment, %



Not evaluable (no tumor assessment follow-up), %



Median time to objective response (months)



Median DOR, months (95% CI) Range

NR 4.1-11+

6.9 (1.5 NR) 1,5-11,1+

DOR=duration of response; NR=not reached.

a4 of 50 patients did not reach first tumor assessment at database lock.

bOf 17 patients with stage disease in the nivolumab + ipilimumab arm, 7 had confirmed partial response after databse lock, resulting in updated ORR of 32.6%.

c1 patient had progressive disease in the spine, requiring surgery.

d1 patient died due to an unrelated adverse event, 1 patient died due to treatment-related myasthenia gravis, 1 patient died due to progressive disease.

e1 patient had an unrelated adverse event leading to permanent discontinuation, and had no post-baseline tumor assessment.


In this PD-L1 unselected SCLC population with progression after PLT-CT, nivolumab monotherapy and nivolumab+ipilimumab were generally well tolerated with manageable toxicity. Rare severe toxicities will require close follow-up. Durable responses occurred with nivolumab monotherapy and in combination with ipilimumab.

Trial Registry

Clinical Trial Number: NCT01928394.

Authors’ Affiliations

Oregon Health & Science University, Portland, OR, USA
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN, USA
START Madrid, Centro Integral Oncológico Clara Campa, Madrid, Spain
Heidelberg University Hospital, Heidelberg, Germany
Istituto Nazionale dei Tumori, Milan, Italy
Dana-Farber Cancer Institute, Boston, MA, USA
Memorial Sloan Kettering Cancer Center, New York, NY, USA
Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
Duke University Medical Center, Durham, NC, USA
Hospital Universitario 12 de Octubre, Madrid, Spain
Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy
Bristol-Myers Squibb, Princeton, NJ, USA
Yale Comprehensive Cancer Center, New Haven, CT, USA


© Taylor et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.