BioNTech/Bristol Myers Squibb and Pfizer are taking different approaches to overall survival in first-line NSCLC trials aimed at building the next PD-(L)1×VEGF bispecific franchise, according to reporting on trial strategy. The split highlights how companies are positioning their primary endpoints for a class that has quickly expanded beyond early-phase expectations. The divergence is likely to matter for regulators and payers because overall survival is generally viewed as the hardest endpoint to validate, while progression-free survival and response metrics can be earlier decision points. Companies appear to be balancing speed, statistical power, and the clinical story they want to tell. For the field, the endpoint strategy is also tied to the wider competitive landscape in immuno-oncology—where China-based late-stage results have raised the stakes for confirmatory studies. As these programs mature, the trial design differences could influence how quickly assets become practice-changing and what evidence requirements will look like in future bispecific approvals.