Tislelizumab (TIS) plus chemotherapy (CT) vs placebo (PBO) plus CT in HER2-negative advanced ormetastatic gastric or gastro-esophageal junction adenocarcinoma (GC/GEJC): PD-L1 biomarker
analysis from RATIONALE-305
Authors: Markus Moehler,1 Do-Youn Oh,2 Ken Kato,3 Josep Tabernero,4 Marcia Cruz Correa,5 Lucjan
Wyrwicz,6 Roberto Pazo-Cid,7 Antonio Cubillo Gracián,8 Ludovic Evesque,9 Lorenzo Fornaro,10 Efrat
Dotan,11 Carys Morgan,12 Liyun Li,13 Yaling Xu,14 Tao Sheng,15 Silu Yang,13 Han Hu,13 Ruihua Xu16Affiliations: 1Johannes Gutenberg-University Clinic, Mainz, Germany; 2Seoul National University
Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, SouthKorea; 3National Cancer Center Hospital, Tokyo, Japan; 4Vall d’Hebron University Hospital, Barcelona,Spain; 5University of Puerto Rico, San Juan, Puerto Rico; 6Narodowy Instytut Onkologii, Warsaw,Poland; 7Hospital Universitario Miguel Servet, Zaragoza, Spain; 8Hospital Universitario HM
Sanchinarro, Madrid, Spain; 9Centre Antoine Lacassagne, Nice, France; 10Azienda OspedalieroUniversitaria Pisana, Pisa, Italy; 11Fox Chase Cancer Center, Temple University Health System,Philadelphia, PA; 12Velindre Cancer Centre, Cardiff, UK; 13BeiGene (Beijing) Co., Ltd, Beijing, China;
14
BeiGene (Shanghai) Co., Ltd, Shanghai, China; 15BeiGene USA, Inc., San Mateo, CA; 16Sun Yat-sen
University Cancer Center State Key Laboratory of Oncology in South China, Collaborative Innovation
Center of Cancer Medicine, Guangzhou, China

ABSTRACT
Background: TIS (an anti–PD-1 antibody) + CT demonstrated significant overall survival (OS) benefitvs PBO + CT as first-line (1L) therapy for advanced GC/GEJC in all randomized patients (pts; HR=0.80)
and pts with PD-L1 Tumor Area Positivity (TAP) score ≥5% (HR=0.71) (phase 3 RATIONALE-305 study,NCT03777657). Here we report exploratory analyses of OS subgroup results by PD-L1 expression
status and concordance between PD-L1 TAP score and combined positive score (CPS).
Methods: Adults with GC/GEJC were randomized (1:1) to IV TIS 200 mg or PBO every 3 weeks +investigator-chosen CT (oxaliplatin + capecitabine or cisplatin + 5-fluorouracil). The primary endpoint
was OS in all randomized pts and in pts with PD-L1 TAP ≥5%. Tissue samples were stained using theVENTANA PD-L1 (SP263) assay. PD-L1 expression was prospectively assessed by TAP and rescoredpost hoc by CPS. OS with exploratory PD-L1 score cutoffs (TAP: 1%, 10%; CPS: 1, 5, 10), concordance
between TAP and CPS at multiple cutoffs, and interclass correlation coefficient (ICC) wereinvestigated.
Results: Of 997 pts randomized (TIS + CT, n=501; PBO + CT, n=496), 281/28.2% and 885/88.8% hadbaseline PD-L1 TAP ≥10% and ≥1%, respectively. At final analysis (min follow-up: 24.6 mo), OSimprovement with TIS + CT vs PBO + CT was observed in subgroups of PD-L1 TAP score ≥10% and≥1% (Table). ICC between TAP and CPS was 0.81 (95% CI 0.79–0.83). TAP and CPS scores showed
substantial concordance in terms of overall percentage agreement and Cohen’s Kappa (N=974).
Conclusions: The addition of TIS to CT as 1L treatment for GC/GEJC improved OS in pts with PD-L1TAP ≥10% and ≥1%. These data, with prior data from pts with PD-L1 TAP ≥5% and all randomized pts,
support TIS + CT as a new 1L treatment option for advanced HER2-negative GC/GEJC. Concordant
TAP and CPS results suggest both methods are viable for clinical PD-L1 expression measurement inpts with GC/GEJC.

ESMO GIEvents/total
PD-L1 status
TAP

TIS + CTPBO + CT

318/432

370/453

52/69

36/43

≥5%

192/274

219/272<5%178/227

187/22484/136

118/145286/365

288/351

≥1%
<1%

≥10%
<10%CPS≥1<1308/420
53/71≥5175/254<5186/237≥10<10PD-L1 concordanceof TAP vs CPS1% vs 1
5% vs 510% vs 10

ESMO GI

100/151261/340Overall %agreement,(95% CI)95 (94–97)
82 (80–85)
85 (83–87)

OS
unstratified,
HR (95% CI)
0.78 (0.67–0.90)
0.98 (0.64–1.50)
0.72 (0.59–0.88)
0.91 (0.74–1.12)
0.57 (0.43–0.76)
0.91 (0.77–1.07)

0.78 (0.67–0.91)
39/49
1.01 (0.66–1.52)
0.73 (0.60–211/269
0.89)
0.89 (0.72–184/214
1.09)
111/138
0.68 (0.52–0.90)
284/3450.87 (0.73–1.03)
Cohen’s Kappa,(95% CI)356/434

0.78 (0.71–0.84)
0.64 (0.60–0.69)
0.64 (0.59–0.69)