A Study of Nivolumab in Participants with Metastatic or Unresectable Bladder Cancer.

Bristol-Myers Squibb
Study Design: 
In the single-arm phase II Checkmate 275 study, patients with metastatic or surgically unresectable UC were treated with nivolumab. Of the 270 patients, 139 (51%) had evaluable TMB ascertained from tumor DNA from pre-treatment archival tumor tissue and matched whole blood samples. TMB was defined by the total number of missense somatic mutations per tumor. In this abstract, the association between TMB and PFS, ORR, and OS was investigated.
The abstract presented at ESMO evaluated the impact of tumor mutation burden (TMB) on nivolumab’s efficacy (PD-1 inhibitor) from the previously conducted Checkmate 275 study.
This study suggests that TMB might enrich for responses to nivolumab that may be independent of PD-L1 expression.
TMB demonstrated a statistically significant positive association with PFS (p=0.005) and ORR (p=0.002) but a statistically insignificant association with OS (p=0.067) even when adjusted for baseline tumor PD-L1 expression. In fact, patients with TMB had high ORR even with low (<1%) PD-L1 expression.