Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial

Antonia, S. J. et al. (2016) Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncology, 17(7), pp. 883-895. (doi: 10.1016/S1470-2045(16)30098-5) (PMID:27269741)

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Abstract

BACKGROUND: Treatments for small-cell lung cancer (SCLC) after failure of platinum-based chemotherapy are limited. We assessed safety and activity of nivolumab and nivolumab plus ipilimumab in patients with SCLC who progressed after one or more prior regimens. METHODS: The SCLC cohort of this phase 1/2 international multiarm open-label trial was conducted at 23 sites. Eligible patients were 18 years of age or older, had limited or extensive-stage SCLC, and had disease progression after at least one prior platinum-containing regimen. Patients received nivolumab (3 mg/kg) every 2 weeks, or nivolumab plus ipilimumab (1 mg/kg plus 1 mg/kg, 1 mg/kg plus 3 mg/kg, or 3 mg/kg plus 1 mg/kg, respectively) every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks. Patients were either assigned to nivolumab monotherapy or assessed in a dose escalating safety phase for the nivolumab/ipilimumab combination beginning at nivolumab-1/ipilimumab-1. Depending on tolerability, patients were then assigned to nivolumab-1/ipilimumab-3 or nivolumab-3/ipilimumab-1. The primary endpoint was objective response rate (ORR). All analyses included patients who were enrolled at least 90 days prior to database lock. This trial is ongoing; an interim analysis is reported here. This study is registered with ClinicalTrials.gov, number NCT01928394. FINDINGS: Between Nov 18, 2013 and July 28, 2015, 216 patients were enrolled and treated (n=98, nivolumab-3; n=3, nivolumab-1/ipilimumab-1; n=61, nivolumab-1/ipilimumab-3; n=54, nivolumab-3/ipilimumab-1). ORRs were 10% (10/98), 23% (14/61), and 19% (10/54) for patients receiving nivolumab-3, nivolumab-1/ipilimumab-3, and nivolumab-3/ipilimumab-1, respectively. In the nivolumab-3, nivolumab-1/ipilimumab-3, and nivolumab-3/ipilimumab-1 cohorts, respectively, 13 (13%), 18 (30%), and 10 (19%) patients reported grade 3 or 4 treatment-related adverse events; across arms, the most commonly reported grade 3 or 4 treatment-related AEs were increased lipase (5 [2%]), diarrhea (4 [2%]), dyspnea (3 [1%]), and pneumonitis (3 [1%]), In the nivolumab-3, nivolumab-1/ipilimumab-3, and nivolumab-3/ipilimumab-1 cohorts, respectively, four (4%), seven (11%), and four (7%) patients discontinued due to treatment-related adverse events. One patient who received nivolumab-1/ipilimumab-3 died from treatment-related myaesthenia gravis. INTERPRETATION: Nivolumab monotherapy and nivolumab plus ipilimumab showed antitumour activity with durable responses and manageable safety profiles in previously treated patients with SCLC. These data suggest a potential new treatment approach for a population of patients with limited treatment options and support the evaluation of nivolumab and nivolumab plus ipilimumab in phase 3 randomised controlled trials in SCLC.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Evans, Professor Jeff
Authors: Antonia, S. J., López-Martin, J. A., Bendell, J., Ott, P. A., Taylor, M., Eder, J. P., Jäger, D., Pietanza, M. C., Le, D. T., de Braud, F., Morse, M. A., Ascierto, P. A., Horn, L., Amin, A., Pillai, R. N., Evans, J., Chau, I., Bono, P., Atmaca, A., Sharma, P., Harbison, C. T., Lin, C.-S., Christensen, O., and Calvo, E.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Lancet Oncology
Publisher:Elsevier
ISSN:1470-2045
ISSN (Online):1474-5488
Published Online:04 June 2016
Copyright Holders:Copyright © 2016 Elsevier
First Published:First published in Lancet Oncology 17(7):883-895
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
573449Experimental Cancer Medicine Centre (ECMC)Thomas EvansCancer Research UK (CAN-RES-UK)15584ICS - EXPERIMENTAL THERAPEUTICS