CHICAGO — First-line therapy with nivolumab in combination with ipilimumab demonstrated clinical activity and a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC), researchers reported at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.1

“Nivolumab monotherapy is approved in the United States and the European Union in adults for locally advanced/metastatic NSCLC with progression on or after platinum-doublet chemotherapy,” said lead investigator Matthew D. Hellmann, MD, medical oncologist at Memorial Sloan Kettering Cancer Center in New York, NY.

Because the combination has demonstrated clinical activity with a manageable safety profile in numerous solid tumors, researchers aimed to evaluate the activity and tolerability of nivolumab alone and in combination with ipilimumab for first-line therapy in patients with advanced NSCLC in a phase 1 study.

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For the CheckMate 012 trial, researchers enrolled previously untreated patients with any NSCLC histology. Previous cohorts included nivolumab plus ipilimumab at varying doses every 3 weeks for 4 cycles, but those combinations were not well tolerated when ipilimumab was given every 3 weeks.

Patients also received nivolumab 1 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks, and 2 new cohorts were opened to administer nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 12 weeks, or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks. All patients in those 3 cohorts received treatment until disease progression or unacceptable toxicity.

Results showed that the objective response rate was 47% (95% CI, 31-64) among the 38 patients who received nivolumab 3 mg/kg plus ipilimumab every 12 weeks and 39% (95% CI, 23-55) among the 39 patients who had nivolumab 3 mg/kg every 2 weeks plus ipilimumab every 6 weeks. Nivolumab monotherapy previously resulted in an objective response rate of 23% (95% CI, 13-37).

“Nivolumab plus ipilimumab has promising efficacy, with objective response seen in 39% to 47% of patients,” Dr Hellmann said.

Median duration of response has not yet been reached, and median progression-free survival was 8.1 months, 3.9 months, and 3.6 months, respectively. Researchers also found that responses were achieved regardless of PD-L1 expression.

“However, efficacy with nivolumab plus ipilimumab is enhanced with increasing PD-L1 expression,” Dr Hellmann added.

In terms of safety, treatment-related adverse events leading to immunotherapy combination discontinuation were comparable to nivolumab monotherapy, and no treatment-related deaths occurred.

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“Importantly, treatment-related grade 3 to 4 adverse events led to discontinuation at a third of the rate seen with older combination arms using higher or more frequent doses of ipilimumab,” Dr Hellmann noted.

Ultimately, nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks was recommended for further assessment in this treatment setting, including in the phase 3 CheckMate 227 trial.                                      


  1. Hellmann MD, Gettinger SN, Goldman JW, et al. CheckMate 012: Safety and efficacy of first-line (1L) nivolumab (nivo; N) and ipilimumab (ipi; I) in advanced (adv) NSCLC. J Clin Oncol. 2016; 34 (suppl; abstr 3001).