Tumor mutational burden
Bristol-Myers Squibb (BMY) has played a major role in positioning the tumor mutational burden (or TMB) as a potential new biomarker across multiple tumor types such as bladder cancer, non-small cell lung cancer (or NSCLC), and small cell lung cancer (or SCLC). The company has managed to demonstrate the efficacy of using this biomarker in terms of progression-free survival, overall survival, and overall response rates, for both Opdivo monotherapy as well as Opdivo-Yervoy combination regimen across multiple clinical trials.
CheckMate-227 trial design
Bristol-Myers Squibb originally planned to have two companion studies in its CheckMate-227 trial:
- Part 1A, consisting of NSCLC patients with PD-L1 expression of greater than or equal to 1%
- Part 1B, consisting of NSCLC patients with PD-L1 expression lesser than 1%
These studies would compare the potential of the Opdivo-low-dose Yervoy combination regimen with Opdivo monotherapy as well as with chemotherapy.
The company later made changes to the trial design and increased number of patients in Part 1a to have more statistically significant and balanced data from PD-L1 expressor patient population. Bristol-Myers Squibb also added a part two to the trial, which included 750 NSCLC patients regardless of PD-L1 expression and histology, to compare an Opdivo-chemotherapy combination regimen with chemotherapy. Finally, the company is performing an integrated analysis of data from both the companion studies in part one of the trial for high TMB patient population.
Based on the new trial design, Bristol-Myers Squibb has determined two co-primary endpoints for the CheckMate-227 trial. The first one was progression-free survival for the Opdivo-Yervoy combination regimen as compared to chemotherapy in TMB high population, which CheckMate-227 has already managed to hit. The second one is the overall survival for Opdivo-Yervoy combination regimen as compared to chemotherapy in the PD-L1 selective patient population. Bristol-Myers Squibb expects to have a data readout for overall survival from Part 1a of the CheckMate-227 trial by the end of 2018 or early 2019.
In the next article, we’ll discuss Bristol-Myers Squibb’s broad research program in first-line NSCLC indication in greater detail.