AACR 2022: TMB not a good biomarker for immune checkpoint inhibitors (RATIONALE 304 study)?

The RATIONALE 304 study is a trial of tislelizumab (an anti-PD-1 antibody) in combination with platinum and pemetrexed versus chemotherapy alone in first-line treatment of patients with stage IIIB or IV non-squamous non-small cell lung cancer (nsq- NSCLC ).

A total of 334 nsq-NSCLC patients were enrolled in the study and randomly assigned in a 2:1 ratio to tislelizumab combined with chemotherapy (group A, n=223) and chemotherapy alone (group B, n=111).

Figure 1 RATIONALE 304 study design

The interim analysis showed that in patients with advanced non-squamous NSCLC, the combination of tislelizumab significantly improved PFS compared with chemotherapy alone (IRC assessment: P=0.

In a preliminary analysis of RATIONALE-304 (NCT03663205), tislelizumab (TIS) plus platinum-based chemotherapy significantly improved clinical outcomes in untreated advanced nsq-NSCLC compared with chemotherapy alone (by independent review committee [ The median progression-free survival [PFS] assessed by IRC] was 9.

The nsq-NSCLC patients were randomly divided into TIS+platinum+pemetrexed group and platinum+pemetrexed group according to the ratio of 2:1

Of the 325 treated patients without EGFR-sensitizing mutations in the RATIONALE-304 study, 177 (54.

In this retrospective analysis, neither tTMB nor bTMB was significantly associated with PFS benefit, suggesting that tTMB and bTMB have limited clinical utility in TIS+chemotherapy as first-line treatment for advanced nsq-NSCLC