BMS withdraws sBLA for Opdivo + Yervoy (low dose) for NSCLC patients with tumor mutational burden.

Following recent discussions with the FDA, BMS announced the voluntary withdrawal of the U.S. supplemental Biologics License Application (sBLA) for the Opdivo (nivolumab) and low-dose Yervoy (ipilimumab) combination for treatment of first-line advanced non-small cell lung cancer (NSCLC) in patients with tumor mutational burden (TMB) in greater than 10 mutations/megabase (mut/Mb)

In October 2018, the company announced the submission of an exploratory overall survival (OS) analysis for the TMB <10 mut mb subgroup to the fda. the fda determined at that time, that the submission of this new information constituted a major amendment to the sbla and extended the review period by three months, moving the prescription drug user fee act date to 20 may 2019. bms needs data from part 1a of the checkmate 227 study, which will not be available during the review period of the application, though expected in the first half of 2019. the withdrawal of the filing raises more questions about the viability of tmb as a biomarker with the fda.>

Further data due 1H 2019 from its Phase III trial, Checkmate-227, will be required for analysis before resubmitting the application.