One-sided P values for the association of TMB and clinical outcomes in pembro-treated patients were 0.154 for ORR, 0.014 for PFS, and 0.018 for OS; the area under the ROC curve ([AUROC] 95% CI) for predicting ORR was 0.58 (0.43-0.73). Two-sided P values for the association of TMB and clinical outcomes in chemo-treated patients were 0.114 for ORR, 0.478 for PFS, and 0.906 for OS; AUROC (95% CI) was 0.43 (0.27-0.59).

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated:...for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.

In multivariate models, TMB, PD-L1, and TcellinfGEP were each independently predictive for ORR (p < 0.001). ORR was higher in patients with high versus low levels of biomarkers… patients with higher versus lower levels of TMB and PD-L1 or TMB and TcellinfGEP had the highest ORRs....TMB and the inflammatory biomarkers PD-L1 and TcellinfGEP, assessed alone or together, may be useful for characterizing clinical response to pembrolizumab in R/M HNSCC.

To characterize genomic determinants of response to pembrolizumab in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 study….TMB, clonality-weighted TMB, and TcellinfGEP were significantly associated with objective response (p=0.0276, p=0.0201, and p=0.006, respectively), and a positive trend was observed between NL and PD-L1 CPS and clinical response (p=0.0550 and p=0.0682, respectively)....TMB and inflammatory biomarkers (TcellinfGEP and PD-L1) may represent distinct and complementary biomarkers predicting response to anti-programmed death 1 therapies in HNSCC.

TMB, PD-L1 and T-cell inflamed GEP were independently predictive of response to pembrolizumab in HNSCC patients, in general regardless of HPV status.