Bristol announced on September24 that Opdivo Phase3 CheckMate-274 adjuvant trial in high-risk, muscle invasive bladder cancer (MIBC) met its primary endpoint of disease-free survival (DFS) in all randomized and PD-L1 ≥1% patients at an interim analysis.
Note earlier this year competitor Roche (covered by Mark Purcell) Tecentriq adjuvant MIBC trial failed to show DFS benefit in intent-to-treat population (HR=0.89) and by PD-L1 status (PD-L1 IC0/1 HR=0.81; PD-L1 IC2/3 HR=1.01). This is the third tumor that Opdivo (fourth for IO) has demonstrated efficacy in the adjuvant setting. Both Opdivo and Keytruda are approved in adjuvant melanoma; Opdivo met the primary endpoint of DFS in adjuvant esophageal/GEJ cancer in CM-577 last month; Keytruda met the coprimary endpoint of pCR in Keynote-522late last year with EFS data expected later this year. Full CM-274 data will be presented at a future medical conference and results will be shared with regulatory authorities. CM-274 will continue for future analysis of the secondary endpoints, including overall survival (OS). We estimate a ~$0.5B US opportunity for adjuvant bladder cancer.
We await CM-816 in neoadjuvant lung and CM-915in adjuvant melanoma readouts in coming months.
CM-816 could be unblinded with pathological complete response (pCR) released in 2H20 if the pCR data meets a certain hurdle as determined by the Data Monitoring Committee. It is unclear if FDA would accept a filing on such data because to date only breast cancer indications have been approved based on pCR endpoints, but we see this as a "free call option." On the other hand, CM-915 already failed on the co-primary endpoint of recurrence-free survival (RFS) in PD-L1<1% melanoma (announced on 11/20/19); the forthcoming data will be in all-comers (all PD-1 status). The trial is testing Opdivo + Yervoy vs. Opdivo as adjuvant treatment in resected, stage 3/ 4 melanoma patients, for which Opdivo and MRK's Keytruda are approved. We plan to compare CM-915 results to KN-054 (Keytruda vs. placebo) cross-trial.