A Study of Tislelizumab in Combination With Chemotherapy Versus Chemotherapy in Advanced Lung Cancer

Summary

An open-label, randomized, multicenter Phase 3 study designed to compare the efficacy and safety of tislelizumab combined with chemotherapy versus chemotherapy only as first-line treatment in advanced squamous non-small cell lung cancer (NSCLC).

Timeline

Start

2018-07-30

Primary completion

2020-09-30

Completion

2023-04-28

Outcome

Met primary endpoint

registry analysis (superiority test); Tislelizumab + Paclitaxel + Carboplatin vs Paclitaxel + Carboplatin; p = 0.0001; Hazard Ratio (HR) 0.52 (95% CI 0.37 to 0.74) NCT03594747 ↗

registry analysis (superiority test); Tislelizumab + Nab-paclitaxel + Carboplatin vs Paclitaxel + Carboplatin; p <0.0001; Hazard Ratio (HR) 0.47 (95% CI 0.33 to 0.67) NCT03594747 ↗

paper At 4-year follow-up, patients with advanced sq-NSCLC who received tislelizumab plus chemotherapy experienced long-term OS and PFS benefits versus chemotherapy alone, despite high crossover rates. PMID 41811656 ↗

Publications

• Background Wang J, Lu S, Yu X, Hu Y, Sun Y, Wang Z, Zhao J, Yu Y, Hu C, Yang K, Feng G, Ying K, Zhuang W, Zhou J, Wu J, Leaw SJ, Zhang J, Lin X, Liang L, Yang N. Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 May 1;7(5):709-717. doi: 10.1001/jamaoncol.2021.0366.
• Background Wang, J, S. Lu, et al. Randomized Phase III Study of Tislelizumab plus Chemotherapy versus Chemotherapy Alone as First-Line Treatment for Advanced Squamous Non-Small Cell Lung Cancer (Sq-NSCLC): RATIONALE-307 Updated Analysis. IOTECH Abstract, Vol. 16 Supplement 1, Dec. 2022. doi.org/10.1016/j.iotech.2022.100244.
• Wang Z, Yu X, Zhao J, Yu Y, Wu J, Ma R, Ma Z, Cui J, Zhang J, Bao Y, Leaw S, Wang J. First-Line Tislelizumab Plus Chemotherapy for Advanced or Metastatic Squamous Non-Small Cell Lung Cancer: 4-Year Long-Term Follow-Up from RATIONALE-307. Oncol Ther. 2026 Jun;14(2):811-825. doi: 10.1007/s40487-026-00424-z. Epub 2026 Mar 11.
• Duan J, Zhang Y, Chen R, Liang L, Huo Y, Lu S, Zhao J, Hu C, Sun Y, Yang K, Chen M, Yu Y, Ying J, Huang R, Ma X, Leaw S, Bai F, Shen Z, Cai S, Gao D, Wang J, Wang Z. Tumor-immune microenvironment and NRF2 associate with clinical efficacy of PD-1 blockade combined with chemotherapy in lung squamous cell carcinoma. Cell Rep Med. 2023 Dec 19;4(12):101302. doi: 10.1016/j.xcrm.2023.101302. Epub 2023 Dec 4.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Nab-paclitaxel	Small molecule	100 mg/m2	Intravenous
Subject	Paclitaxel	Small molecule	175 mg/m2	Intravenous
Subject	Tislelizumab	Monoclonal antibody	200 mg	Intravenous
Background	Carboplatin	Small molecule	5 unknown	Intravenous

Indications