RATIONALE-307 Long-term Outcomes: First-line Tislelizumab (TIS) Plus Chemotherapy (chemo) vsChemo Alone for Advanced Squamous (sq) NSCLCAuthors: Z. Wang1, X. Yu2, J. Zhao3, Y. Yu4, J. Wu5, R. Ma6, Z. Ma7, J. Cui8, N. Zhao9, L. Liang10, J. Fan11, J.

Wang1; 1Department of Medical Oncology, Chinese Academy of Medical Sciences and Peking Union

Medical College - National Cancer Center, Cancer Hospital, Beijing, China, 2Department of medical
oncology, Zhejiang Cancer Hospital - Cancer Research Institute, Hangzhou, China, 3Department ofMedical Oncology, Beijing Cancer Hospital, Beijing, China, 4Department of Medical Oncology, Harbin

Medical University Cancer Hospital, Harbin, China, 5Department of Medical Oncology, The 1stAffiliated Hospital of Xiamen University, Xiamen, China, 6Department of Chest Internal Medicine,Liaoning Cancer Hospital & Institute, Shenyang, China, 7Department of Medical Oncology, Henan

Cancer Hospital/Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China, 8Cancer

Center, The First Hospital of Jilin University, Changchun, China, 9Global Statistics & Data Science,BeiGene (Shanghai) Co., Ltd., Shanghai, China, 10Clinical Biomarker Science and CDx Development,BeiGene (Beijing) Co., Ltd., Beijing, China, Beijing, China, 11Medical Affairs, BeiGene, Ltd. - ClinicalDevelopment and Regulatory Office, Beijing, China
Background

First-line TIS + chemo has improved PFS vs chemo alone for advanced sq-NSCLC in RATIONALE-307(NCT03594747). Here, we reported the long-term outcomes in the ITT population and in patients (pts) withlong-term exposure (LTE) to TIS.
Methods

Pts were randomized 1:1:1 to receive TIS + paclitaxel + carboplatin (T+PC arm), TIS + nab-paclitaxel +carboplatin (T+nPC arm), or paclitaxel + carboplatin (PC arm). The primary endpoint was PFS; OS was asecondary endpoint. Crossover from PC arm to TIS monotherapy was permitted after PD, OS was adjusted by
two-stage method. LTE was defined as ≥35 cycles of TIS treatment. PD-L1 expression, TMB, gene expression
profiling, and genetic alterations were assessed on baseline tumor samples.
Results
Among the 360 randomized pts (T+PC arm, n=120; T+nPC arm, n=119; PC arm, n=121), median time fromrandomization to data cutoff (Apr 28, 2023) was 50.3 mo (range, 46.5-57.0). 58.7% (71/121) of pts crossed overto receive TIS monotherapy. The improvement in PFS with TIS + chemo vs chemo (mPFS, 5.5 mo) was
maintained, with mPFS of 7.7 mo (HR, 0.45; 95% CI 0.33-0.62) for T+PC and 9.5 mo (HR, 0.45; 95% CI 0.33-0.62)
for T+nPC. Median OS was 26.1 vs 19.4 mo with T+PC vs PC (HR, 0.67; 95% CI 0.49-0.92), and 23.3 vs 19.4 mowith T+nPC vs PC (HR, 0.82; 95% CI, 0.60-1.11). 4-y OS rates were 32.2% for T+PC, 26.0% for T+nPC, and 19.2%for PC. After adjusting for the in-study crossover effect, the stratified HRs were 0.53 (95% CI 0.34-0.84) and 0.65
(95% CI 0.39-1.07), respectively. 42 (17.6%) pts with LTE were observed in TIS+chemo arms, with mediantreatment cycles of 58 (range 37-71), 4-y OS rate of 97.5%, and ORR of 100% (CR, n=11; PR, n=31). The profileof imAEs in LTE pts was similar to the overall population of TIS + chemo arms. Higher PD-L1 expression, tumor
inflammation signature levels (TISL), and enriched FAT1 mutations (LTE vs non-LTE, 34.6% [9/26] vs 15.4%[23/149]) were observed in LTE pts.
Conclusions
The OS benefit favoring TIS + chemo was well maintained, with clinically promising 4-y OS rates of 32.2% withT+PC and 26.0% withT+nPC. LTE pts achieved higher ORR and long-term survival, with higher baseline PD-L1
expression and TISL; the FAT1 mutation may play an indicative role for LTE, which needs to be further explored.

ESMO 2024