IASLC 2017: CheckMate-032: Nivolumab Alone or With Ipilimumab in Recurrent SCLC With High Tumor Mutation Burden

Key Points

  • Patients with high TMB who received nivolumab plus ipilimumab had an objective response rate of 46%; the objective response rate was 16% and 22% in patients with medium and low levels of TMB, respectively.
  • Patients with high TMB who received nivolumab had an objective response rate of 21%; the objective response rate was 7% and 5%, in patients with medium and low levels of TMB, respectively.
  • In patients with high TMB who received nivolumab plus ipilimumab, 62% were alive at 1 year; 20% and 23% of patients with medium and low levels of TMB were alive at 1 year, respectively. In patients with high TMB who received nivolumab, 35% were alive at 1 year; 26% and 22% of patients with medium and low levels of TMB were alive at 1 year, respectively.

At the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer in Yokohama, Japan, Bristol-Myers Squibb announced data evaluating nivolumab (Opdivo) and nivolumab plus ipilimumab (Yervoy) in previously treated small cell lung cancer (SCLC) patients whose tumors were evaluable for tumor mutation burden (TMB).

Over time, cancer cells accumulate mutations that are not seen in normal cells of the body. Tumor mutation burden is a measurement of the quantity of mutations carried by tumor cells, and is one type of biomarker that may help predict the likelihood a patient responds to immuno-oncology therapies.

CheckMate-032 is an ongoing phase I/II open-label trial evaluating the safety and efficacy of nivolumab monotherapy 3 mg/kg every 2 weeks or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four cycles in advanced or metastatic solid tumors. All patients were treated until disease progression or unacceptable toxicity. The trial included both programmed cell death ligand 1 (PD-L1) expressors and nonexpressors. The primary objective was objective response rate as assessed by a blinded independent central review, for which results were previously presented. Secondary objectives included safety, overall survival, progression-free survival, and duration of response. Biomarker analysis was an exploratory objective.

Clinical Findings

In the pooled intent-to-treat population (n = 401), the objective response rate was 11% with nivolumab alone and 22% with the combination. Among the intent-to-treat population, 211 (53%) patients had an evaluable TMB result for these analyses and were divided into subgroups of high, medium, and low levels of TMB.

Patients with high TMB who received nivolumab plus ipilimumab had an objective response rate of 46%; the objective response rate was 16% and 22% in patients with medium and low levels of TMB, respectively. Patients with high TMB who received nivolumab had an objective response rate of 21%; the objective response rate was 7% and 5% in patients with medium and low levels of TMB, respectively. In patients with high TMB who received nivolumab plus ipilimumab, 62% were alive at 1 year; 20% and 23% of patients with medium and low levels of TMB were alive at 1 year, respectively. In patients with high TMB who received nivolumab, 35% were alive at 1 year; 26% and 22% of patients with medium and low levels of TMB were alive at 1 year, respectively. No new safety data were presented in this analysis.

Progression-free survival data for the TMB-evaluable patient population were also presented at the WCLC. Patients with high TMB who received nivolumab plus ipilimumab had a 1-year progression-free survival rate of 30%; the rates were 8% and 6% in patients with medium and low TMB levels, respectively. Patients with high TMB who received nivolumab had a 1-year progression-free survival rate of 21%; the rate was 3% in patients with medium TMB level; progression-free survival was not evaluable in patents with low TMB level.

“These exploratory TMB data from CheckMate-032 are the first to show the potential of using mutation burden to predict response in some patients with the combination of two [immuno-oncology] agents,” said Matthew D. Hellmann, MD, study investigator, Memorial Sloan Kettering Cancer Center. “Further investigation is warranted to explore the application of this marker across lung cancers, and in the setting of both [immuno-oncology] combination[s] and monotherapy.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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