Tislelizumab (TIS) + chemotherapy (CT) vs placebo (PBO) + CT in HER2-negative advanced or metastatic gastric or
gastro-oesophageal junction adenocarcinoma (GC/GEJC): RATIONALE-305 study minimum 3-year survival followup
Authors: Marcia Cruz Correa,1 Do-Youn Oh,2 Ken Kato,3 Josep Tabernero,4 Anastasia V Zimina,5 Yuxian Bai6 JianhuaShi,7 Keun-wook Lee,8 Hidekazu Hirano,9 David Spigel,10 Lucjan Wyrwicz,11 Roberto Pazo-Cid,12 Antonio CubilloGracián,13 Liyun Li,14 Yaling Xu,15 Tao Sheng,16 Silu Yang,14 Ruihua Xu,17 Markus Moehler18 on behalf of theRATIONALE-305 Investigators

Affiliations:
1. University of Puerto Rico, San Juan, Puerto Rico
2. Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine,
Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, SouthKorea
3. Department of Head and Neck, Esophageal Medical Oncology and Gastrointestinal Medical Oncology,
National Cancer Center Hospital, Tokyo, Japan
4. Medical Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain
5. BHI of Omsk Region Clinical Oncology Dispensary, Omsk, Russia
6. Harbin Medical University Cancer Hospital, Harbin, China
7. Linyi Cancer Hospital, Linyi, China
8. Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, SouthKorea
9. Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
10. Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN, USA
11. Narodowy Instytut Onkologii, Warsaw, Poland
12. Hospital Universitario Miguel Servet, Zaragoza, Spain
13. Hospital Universitario HM Sanchinarro, Madrid, Spain
14. BeiGene (Beijing) Co., Ltd, Beijing, China
15. BeiGene (Shanghai) Co., Ltd, Shanghai, China
16. BeiGene USA, Inc., San Mateo, CA, USA
17. Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology inSouth China, Collaborative Innovation Center of Cancer Medicine, Research Unit of Precision Diagnosis andTreatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China
18. Gastrointestinal Oncology, Johannes Gutenberg-University Clinic, Mainz, Germany
Background
TIS (an anti–programmed cell death protein 1 antibody) + CT demonstrated significant overall survival (OS) benefit vsPBO + CT as first-line (1L) therapy for advanced GC/GEJC in all randomized patients (pts; hazard ratio [HR], 0.80) andpts with PD-L1 Tumour Area Positivity (TAP) score ≥5% (HR, 0.71) in the phase 3 RATIONALE-305 study

ESMO 20241(NCT03777657). 2-yr OS rates for TIS + CT vs PBO + CT were 32.7% vs 23.4%, respectively. We report efficacy andsafety after a minimum 3-yr follow up.
Methods
Adults with locally advanced, nonresectable or metastatic, HER2-negative, untreated GC/GEJC were randomized(1:1) to intravenous TIS 200 mg or PBO every 3 wks + investigator-chosen CT (oxaliplatin + capecitabine or cisplatin +5-fluorouracil). TAP score was evaluated in tumour tissue using the VENTANA PD-L1 (SP263) assay. Primary endpoint
was OS in all randomized pts and pts with PD-L1 TAP ≥5%. Secondary endpoints included investigator-assessed
progression-free survival (PFS), objective response rate, duration of response (DoR) per Response Evaluation Criteria
In Solid Tumors v1.1, and safety.
Results
A total of 997 pts were randomized (TIS + CT, n=501; PBO + CT, n=496). At 3-yr follow up (min: 36.6 mo),
improvements in OS, PFS, and DoR in TIS + CT vs PBO + CT (Table) were maintained. Grade ≥3 treatment-related
adverse events (TRAEs) were similar in both arms, occurring in 269/498 pts (54.0%) with TIS + CT and 246/494 pts(49.8%) with PBO + CT; TRAEs led to any treatment discontinuation in 16.7% vs 8.1% and led to death in 1.2% vs0.4%, respectively.
Conclusions
After a minimum 3-yr follow up, TIS + CT as 1L treatment for GC/GEJC continued to demonstrate clinicallymeaningful improvements in OS, PFS, and DoR compared with PBO + CT, with no new safety signals. These long-term
data further support TIS + CT as a new 1L treatment option for advanced HER2-negative GC/GEJC.
TableMedian OS, mo (95% CI)
HR (95% CI)a
OS rate at 36 mo, % (95% CI)
Median PFS, mo (95% CI)bHR (95% CI)a
PFS at 36 mo (95% CI)
Objective response rate, % (95% CI)bMedian DoR, mo (95% CI)a
Remaining in response at 36 mo, %(95% CI)
aStratified.
b
Investigator evaluated.

ESMO 2024

TIS + CT
(n=501)15.0 (13.6, 16.5)
20.7 (17.1, 24.4)
6.9 (5.7, 7.2)
15.0 (11.6, 18.8)
47.3 (42.9, 51.8)
8.6 (7.9, 11.1)
24.5 (18.8, 30.6)

0.79 (0.69, 0.90)
0.79 (0.68, 0.91)

PBO + CT(n=496)12.9 (12.1, 14.1)
13.4 (10.5, 16.6)
6.2 (5.6, 6.9)
7.5 (5.1, 10.5)
40.5 (36.2, 45.0)
7.2 (6.0, 8.5)
14.4 (9.3, 20.5)

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