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

Background

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-L1^high, 14^th arm) or with TMB ≥10 mut/Mb & PD-L1 expression <50% (TMB^high, 15^th arm).

Methods

Patients received sintilimab monotherapy 200mg every 21 days. The primary objective was objective response rate (ORR). To determine whether sintilimab monotherapy has sufficient activity, we used Simon's minimax two-stage to calculate sample size for these two treatments cohorts.

Results

Between May 29, 2019 and January 6, 2022，831 untreated advanced NSCLC patients were screened with tumor tissue by next-generation sequencing. 63 patients were enrolled and received sintilimab monotherapy in PD-L1^high arm (n = 34) or TMB^high arm (n = 29). As the cutoff data of October 31, 2023, the median follow-up is 21.6 months. The primary endpoint was reached with a confirmed ORR of 47.1% (16/34) and 37.9% (11/29) in PD-L1^high and TMB^high arms, respectively. The median progression-free survival (PFS) was 6.9 months and 14.1 months; the median overall survival (OS) was NR and 37.8 months in PD-L1^high and TMB^high 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.

Conclusions

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.

Clinical trial identification

NCT03574402.

Legal entity responsible for the study

Chinese Thoracic Oncology Group (CTONG).

Funding

This work was funded by Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (2017B030314120, Yi-Long Wu), Guangdong Provincial People's Hospital Scientific Research Funds for Leading Medical Talents in Guangdong Province (KJ012019426, Yi-Long Wu), National Natural Science Foundation of China (Grant No. 82072562, Qing Zhou), the High-Level Hospital Construction Project (DFJH201810, Qing Zhou), and the National Natural Science Foundation of China (82202997, Si-Yang Maggie Liu).

Disclosure

Q. Zhou: Financial Interests, Personal, Invited Speaker: BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi. W. Zhong: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Eli Lilly and Pfizer. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Pfizer; and personal fees from Boehringer Ingelheim, Eli Lilly, Hengrui, MSD, Sanofi, and Roche. All other authors have declared no conflicts of interest.