75P PD-L1 expression and TMB guided first-line sintilimab monotherapy for advanced NSCLC in a multi-center, phase II umbrella trial (CTONG 1702)

The use of immune checkpoint inhibitors including PD-1 and PD-L1 inhibitors is recommended for the treatment of previously untreated advanced non-small cell lung cancer (NSCLC) patients. The immunohistochemical detection of PD-L1 expression on tumor cells has emerged as the most widely utilized biomarker in clinical practice. However, the predictive value of tumor mutation burden (TMB) remains controversial. Here, we reported the result of two cohorts of an umbrella trial, to evaluate the efficacy and safety of sintilimab monotherapy in untreated NSCLC with PD-L1 expression ≥50% (PD-L1high, 14th arm) or with TMB ≥10 mut/Mb the median overall survival (OS) was NR and 37.8 months in PD-L1high and TMBhigh arms, respectively. Treatment-related adverse events with grade ≥3 occurred in 19% (12/63) patients, which was 14.7% (5/34) and 24.1% (7/29) patients in these two arms. The most common adverse events are rash and increased glutamic pyruvic transaminase. In this prospective trial, PD-L1 high expression is a good biomarker for PD-1 inhibitor monotherapy for untreated advanced NSCLC; high TMB also seems to be a predictive marker for PD-1 inhibitor monotherapy, that could achieve long PFS and OS.