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CheckMate 032: Efficacy of nivolumab is enhanced in SCLC patients with high TMB with or without Ipilimumab

New research showed that among small cell lung cancer (SCLC) patients, the efficacy of using nivolumab with or without (±) ipilimumab was enhanced among those with a high tumor mutation burden (TMB).
Initial findings from CheckMate 032, a phase I/II clinical trial evaluating nivolumab ± ipilimumab in solid tumors, showed that this treatment is promising. However, there have been no clear biomarkers to predict patient response. The researchers chose to use an exploratory analysis of CheckMate 032 to search for improved biomarkers in SCLC. CheckMate 032 evaluated treatment with nivolumab ± ipilimumab in both non-randomized and randomized cohorts, which the researchers pooled for the analysis. Additionally, they conducted whole exome sequencing (WES) on tumors and matched blood samples and equally divided patients into low, medium and high TMB cohorts.


The researchers found that among the patients with an evaluable TMB result who were treated with only nivolumab, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were improved in the high TMB cohort as compared to the medium and low TMB cohorts (ORR: 21.3 % vs 6.8 % and 4.8 %; 1-year PFS: 21.2 % vs 3.1 % and not calculable; 1-year OS: 35.2 % vs 26.0 % and 22.1 %). Enhanced benefits in the high TMB cohort were seen most dramatically among those treated with nivolumab and ipilimumab – the response rate was 46.2 % and 1 year overall survival was 62.4 %. Additionally, the researchers found that in each cohort of TMB, nivolumab plus ipilimumab outperformed nivolumab treatment alone. Their findings highlight that high TMB is associated with improved responses to nivolumab ± ipilimumab in patients with SCLC and suggest that TMB may be a relevant biomarker across all patients with lung cancers.
“The results from our study provide the clearest evidence to date demonstrating the power of TMB as a biomarker”, said presenting author Dr. Naiyer Rizvi. “This may even begin to impact prescribing practice in SCLC by clarifying the benefit that can be achieved for some patients, encouraging molecular testing for estimating mutation burden in SCLC and using greater precision to identify subgroups of patients with SCLC who may exceptionally benefit from nivolumab with impilimumab.”

Rizvi N et al., abstract OA 07.03a: Impact of Tumor Mutation Burden on the Efficacy of Nivolumab or Nivolumab + Ipilimumab in Small Cell Lung Cancer: An Exploratory Analysis of CheckMate 032