The stoppage at an interim analysis of Bristol-Myers Squibb’s’ CHECKMATE-214 trial provides meaningful information into assessing the potential fro success of Northwest Biotherapeutics’ phase 3, DCVax-L trial. CHECKMATE-214 compared a combination the immunotherapy drugs Opdivo and Yervoy to Sutent (standard of care) in previously untreated, advanced or metastatic renal cell carcinoma (RCC). The trial was stopped at an interim analysis because it reached statistical significance on its secondary endpoint of overall survival. The results were not statistically significant on the primary endpoint of progression free survival.
Why is this important to NWBO? Like Checkmate-214, the DCVax-L phase 3 trial has a primary endpoint of progression free survival and a secondary endpoint of overall survival with both endpoints powered for significance. As in CHECKMATE-214, results for immunotherapy drugs have been inconsistent on achieving PFS. As I noted in my recent report, “Northwest Biotherapeutics: Why I Believe That the Phase 3 Trial of DCVax-L in Newly Diagnosed Glioblastoma Patients Has a Very Good Chance for Success”, unblinded data from the phase 3 DCVax-L trial indicates that patients appear to be living longer than expected. In that report, I suggested that DCVax-L could be approved even if the trial missed on PFS, if the OS results were encouraging. The results from CHECKMATE-214 reinforce my view.
NWBO has elected to let the phase 3 trial continue even though it has reached the number of PFS and OS events that were prospectively determined to be sufficient to achieve statistical significance. As explained in my report, lengthening the trial increases the potential for statistical significance in OS. There have been questions raised as to why NWBO has not stopped the trial, but having come this far, they want to maximize the potential for success.
This is obviously a positive for BMY as the Company has a huge clinical trial bet that immunotherapy combinations will improve outcomes versus standard of care. This is certainly the case in this trial. These results also augur well for the potential for positive results on OS for BMY’s CHECKMATE-227 trial and Astra-Zeneca’s MYSTIC trial (which earlier missed on PFS). Both of these trials compare anti-PDL-1 and anti-CTLA-4 immunotherapy combinations to standard of care in first line non-small cell lung cancer. The interim readout for both PFS and OS in CHECKMATE-227 could occur by the end of 2017 and the OS results in MYSTIC in 1H-2018. Success in CHECKMATE-227 could have an enormous impact on BMY. It would reestablish BMY as the leader in non-small cell lung cancer over Merck.
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