Pfizer's PD-1 Inhibitor Shows Mixed Results in Phase 3 Bladder Cancer Trial

Pfizer has reported mixed results from a phase 3 trial evaluating its PD-1 inhibitor, sasanlimab, in combination with Bacillus Calmette-Guérin (BCG) for the treatment of high-risk, non-muscle invasive bladder cancer. The study demonstrated a significant reduction in disease-related events but fell short on secondary endpoints, including overall survival.

Primary Endpoint Success

The trial's primary endpoint of event-free survival (EFS) was met, with patients receiving sasanlimab plus induction and maintenance doses of BCG showing a 32% reduction in the risk of disease-related events compared to the control group. At 36 months, the probability of being free from high-grade disease recurrence, disease progression, persistence of carcinoma in situ, or death due to any cause was 82.1% in the sasanlimab plus BCG arm, versus 74.8% in the control cohort.

Secondary Endpoint Challenges

Despite the positive primary outcome, the study encountered setbacks in its secondary endpoints:

1. A third cohort receiving sasanlimab and BCG induction without maintenance doses showed no improvement in EFS compared to the standard-of-care arm, highlighting the importance of BCG maintenance in the treatment regimen.

2. Overall survival, a key secondary endpoint, showed no significant difference between the sasanlimab and standard-of-care groups after a median follow-up of 40.9 months.

Safety Profile and Adverse Events

The overall safety profile of sasanlimab plus BCG was generally consistent with existing evidence on the two treatments. However, the rate of serious treatment-related adverse events was notably higher in the sasanlimab plus BCG induction and maintenance arm (17.7%) compared to the control group (1.4%).

Hepatitis and pancreatitis were identified as the most common grade 3 or 4 immune-mediated adverse events in the sasanlimab arms. Most cases resolved with thyroid hormone supplementation.

Regulatory Implications and Future Prospects

Pfizer has shared the results with health authorities to support potential regulatory filings. If approved, sasanlimab could become the first PD-1 inhibitor approved for this indication, potentially advancing Pfizer's plans to use the drug in combination with its antibody-drug conjugates.

The company continues to track overall survival data through the final analysis of the trial, which may provide additional insights into the long-term efficacy of the treatment.