Findings from an ongoing Phase III study investigating first-line non-small cell lung cancer (NSCLC) patients who have a high tumor mutation burden (TMB) have been announced by Bristol-Myers Squibb (NY, USA), demonstrating promising progression-free survival rates.
The CheckMate-227 study enrolled over 2500 non-small cell lung cancer (NSCLC) patients, randomized across squamous and non-squamous histologies, treated with a combination of Opdivo® (nivolumab) and Yervoy® (ipilimumab) versus standard chemotherapy.
The patients also expressed high TMB, regardless of PD-L1 expression. TMB is classified as ten or more mutations per megabase, a measure which is emerging as a useful oncologic biomarker.
Bristol-Myers Squibb stated that the current findings are based on Part 1 of the trial’s investigation, comprising Part 1a, examining Opdivo and Yervoy and monotherapy versus chemotherapy in patients whose tumors express PD-L1, and Part 1b, which focuses on Opdivo plus Yervoy as well as Opdivo and chemotherapy in patients whose tumors do not express PD-L1. Part 2 aims to investigate Opdivo combined with chemotherapy versus chemotherapy alone, with a primary endpoint of improved overall survival.
Part 1 met its co-primary endpoint, achieving superior rates of progression-free survival following Opdivo and Yervoy combinational therapy, compared with chemotherapy.
In those NSCLC patients with TMB-evaluable tumors, approximately 45% expressed high levels of TMB. “TMB has emerged as an important biomarker for the activity of immunotherapy. For the first time, this Phase 3 study shows superior progression-free survival with first-line combination immunotherapy in a predefined population of NSCLC patients with high TMB,” explained study investigator Matthew D. Hellman (Memorial Sloan Kettering Cancer Center, NY, USA).
“CheckMate-227 showed that TMB is an important, independent predictive biomarker that can identify a population of first-line NSCLC patients who may benefit from the nivolumab plus ipilimumab combination.”
Following preliminary analysis for overall survival, the Data Monitoring Committee has recommended the continuation of the trial.
Despite the initial positive reaction to the trial, many are now questioning the fact that Bristol-Myers Squibb changed the main measure of success in the trial. Following this, Bristol-Myers Squibb has released a statement, find out more about reactions to the trial here.