...Cohort 1: Advanced/metastatic cancers with high TMB expression i....

The clinical data showed that MPR patients with DDR mutation had longer DFS after sintilimab plus chemotherapy therapies (18.4±5.41 months, X-squared=9.8, P=0.02034). DDR mutation, TMB and TCR richness revealed better sensitivity and specificity to classify patients achieving MPR after neoadjuvant chemoimmunotherapy (AUC=1.000, AUC=0.796, AUC=0.773, respectively)....This study confirmed the superiority of neoadjuvant chemoimmunotherapy in patients with potentially resectable stage IIIB NSCLC in terms of MPR. TCR repertoire, TMB and DDR mutation were associated with pathologic response to neoadjuvant chemoimmunotherapy as biomarkers for effective anti-tumor immunity.

Pre-immunotherapy treatment tumor samples from twenty-nine NSCLC patients who received neoadjuvant immunotherapy with sintilimab, an anti-PD-1 drug, were subjected to targeted DNA sequencing and PD-L1 immunochemistry staining...marginally higher TMB was identified in patients with MPR (p = 0.05, Mann–Whitney U test; Fig. 1f). We also observed that all 4 patients with high TMB (>12 mut/Mb) achieved MPR (p = 0.01, Fisher’s exact test; Fig. 1g, h).

...we presented the two-year follow-up outcomes from a phase 1b study of sintilimab, an anti-PD-1 inhibitor in the neoadjuvant setting of NSCLC....Pts with tumor mutation burden (TMB) ≥10 mutations/Mb and PD-L1 tumor proportion score (TPS)≥50% tended to have a better 2-yr DFS rate compared to those with TMB<10 and TPS<50. [table]...the same trend was observed with DFS among different subgroups, and patients with TMB ≥10 mutations/Mb had a significant improved EFS (HR 0.125[95% CI 0.02,1.03], P=0.0222).