RATIONALE-315: Event-Free Survival (EFS) and Overall Survival (OS) of Neoadjuvant Tislelizumab (TIS) plus
Chemotherapy (CT) with Adjuvant TIS in Resectable Non-Small Cell Lung Cancer (NSCLC)
Authors: Dongsheng Yue,1 Wenxiang Wang,2 Hongxu Liu,3 Qixun Chen,4 Chun Chen,5 Lunxu Liu,6 Peng Zhang,7Guofang Zhao,8 Fan Yang,9 Guang Han,10 Ying Cheng,11 Bentong Yu,12 Yue Yang,13 Haiquan Chen,14 Jie Jiang,15 BinYao,16 Shengfei Wang,17 Ruihua Wang,17 Wenjuan Zheng,16 Changli Wang1, on behalf of the RATIONALE-315
Investigators

Affiliations:
1. Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
2. Hunan Cancer Hospital, Hunan, China
3. Liaoning Cancer Hospital and Institute, Shenyang, China
4. Zhejiang Cancer Hospital, Hangzhou, China
5. Fujian Medical University Union Hospital, Fuzhou, China
6. West China Hospital, Sichuan University, Chengdu, China
7. Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
8. Ningbo No.2 Hospital, Ningbo, China
9. Peking University People’s Hospital, Beijing, China
10. Hubei Cancer Hospital, Wuhan, China
11. Jilin Cancer Hospital, Changchun, China
12. The First Affiliated Hospital of Nanchang University, Nanchang, China
13. Beijing Cancer Hospital, Beijing, China
14. Fudan University Shanghai Cancer Center, Shanghai, China
15. The First Affiliated Hospital of Xiamen University, Xiamen, China
16. BeiGene (Beijing) Co., Ltd, Beijing, China
17. BeiGene (Shanghai) Co., Ltd, Shanghai, China
Background
The RATIONALE-315 study (NCT04379635) compared the efficacy and safety of neoadjuvant TIS (anti-PD-1) plus CTand adjuvant TIS vs placebo plus CT in patients with resectable NSCLC; here we report interim results for EFS and OS.
Methods
Patients with treatment-naïve resectable stage II–IIIA NSCLC eligible for platinum-doublet CT with no known EGFR
mutations or ALK gene translocations were randomised (1:1) to either 3–4 cycles of neoadjuvant TIS 200 mg orplacebo (IV Q3W) plus CT, then surgery and ≤8 cycles of adjuvant TIS 400 mg or placebo (IV Q6W). Dual primary
endpoints were EFS by blinded independent central review and major pathological response by blinded independentpathology review. Secondary endpoints included pathological complete response, OS and safety.
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Results
As of 21 Aug 2023 (median follow-up: 22.0 mo), 453 patients were randomized (TIS, n=226; placebo, n=227). Of
these, 452 received neoadjuvant treatment (n=226 both arms [99.8%]), 421 (92.9%) completed neoadjuvant
treatment (TIS, n=211 [93.4%]; placebo, n=210 [92.5%]), 363 (80.1%) had surgery (TIS, n=190 [84.1%]; placebo,n=173 [76.2%]), 315 (69.5%) received adjuvant treatment (TIS, n=168 [74.3%]; placebo, n=147 [64.8%]) and 207(45.7%) completed adjuvant treatment (TIS, n=106 [46.9%]; placebo, n=101 [44.5%]).
Median EFS or OS were not reached for either arm; however, a statistically significant difference in EFS (HR [95% CI],0.56 [0.40–0.79]; 1-sided P=.0003) and an OS benefit trend (HR [95% CI], 0.62 [0.39–0.98]; 1-sided P=.0193) wereobserved favouring TIS. In the safety population (n=226 both arms), 224 (99.1%) patients on TIS vs 225 (99.6%) onplacebo experienced ≥1 treatment-related adverse event (TRAE); 163 (72.1%) vs 150 (66.4%) experienced Grade ≥3TRAEs and 35 (15.5%) vs 18 (8.0%) experienced serious TRAEs, respectively.

Conclusions
Neoadjuvant TIS plus CT with adjuvant TIS demonstrated a clinically meaningful and statistically significant benefit
for EFS and an OS benefit trend vs placebo plus CT. Regimen safety was manageable and consistent with known
treatment risks. These data support this combination as a new standard of care for patients with resectable NSCLC.

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