First-Line Tislelizumab Plus Chemotherapy in
Gastric/Gastroesophageal Junction Cancer:
RATIONALE-305 Asian SubgroupKen Kato,1 Yuxian Bai,2 Jianhua Shi,3 Keun-Wook Lee,4 Jufeng Wang,5 Hongming Pan,6 Sun Young Rha,7 Ruixing Zhang,8 Hidekazu Hirano,1 Kensei
Yamaguchi,9 Zengqing Guo,10 Yi Ba,11 Lei Yang,12 Hiroshi Tsukuda,13 Yaling Xu,14 Tao Sheng,15 Silu Yang,14 Liyun Li,14 Do-Youn Oh,16 Rui-Hua Xu17National Cancer Center Hospital, Tokyo, Japan; 2Harbin Medical University Cancer Hospital, Harbin, China; 3Linyi Cancer Hospital, Linyi, China; 4Seoul National University College ofMedicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 5Henan Cancer Hospital, Zhengzhou, China; 6Sir Run Run Shaw Hospital, Zhejiang University
School of Medicine, Hangzhou, China; 7Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea; 8Fourth Hospital of Hebei Medical University, Shijiazhuang,China; 9Cancer Institute Hospital of JFCR, Tokyo, Japan; 10Fujian Cancer Hospital, Fuzhou, China; 11Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; 12Nantong
Cancer Hospital, Nantong, China; 13Izumi City General Hospital, Izumi, Japan; 14BeiGene (Beijing) Co., Ltd., Beijing, China;
15
BeiGene USA, Inc., Boston, MA, USA; 16Seoul National University Hospital, Cancer Research Institute, Seoul National
Presented at the Asia Pacific Gastroenterology
University College of Medicine, Seoul, Republic of Korea; 17Sun Yat-sen University Cancer Center State Key Laboratory ofCancer Summit (APGCS); 29-31 August 2024; Singapore
Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
1• In Asian patients in the RATIONALE-305 study– Tislelizumab plus chemotherapy showed an improvement in overall survival (OS) versus placebo plus chemotherapy in both the intent-to-treat (ITT) and programmed
death-ligand 1 (PD-L1) score ≥5% populations– Additionally, tislelizumab plus chemotherapy demonstrated improved progression-free survival (PFS), favorable response rates, and more durable antitumor responses versus
placebo plus chemotherapy– Tislelizumab plus chemotherapy also showed a manageable safety profile, with no new safety signals identified• The efficacy and safety results in the Asian patient subgroup were consistent with the results in the overall study population, suggesting this combination may be a first-line
treatment option for Asian patients with advanced gastric/gastroesophageal junction cancer (GC/GEJC)1• An improvement in OS was observed with tislelizumab plus chemotherapy versus placebo plus
chemotherapy in the ITT population (Figure 3)

Introduction• Gastric cancer is one of the leading causes of cancer-related deaths worldwide; Asia has a notably
higher incidence and mortality rate of GC, and the disease is of particular concern in China,
South Korea, and Japan2-5Figure 3. Overall Survival: Asian Subgroup (ITT Population)
1.0• Prior to the introduction of immunotherapy, platinum plus fluoropyrimidine chemotherapy was thestandard first-line therapy for advanced GC/GEJC, with a median OS of less than 12 months6-8• The RATIONALE-305 study (NCT03777657) met its primary endpoint, showing significant improvement inOS with tislelizumab plus chemotherapy versus placebo plus chemotherapy in the PD-L1 ≥5% population
at interim analysis, and in the ITT population at final analysis, with favorable PFS1,9• Overall, results of the final analysis supported tislelizumab plus chemotherapy as a potential first-line
treatment option for patients with advanced GC/GEJC1• Here, we present results from the Asian patient subgroup of the RATIONALE-305 study at final analysis

0.9

Events,n (%)

Median OS(95% CI),
Monthsa

274 (72.9)

16.4 (14.4-18.0)

PBO + chemo
298 (80.1)(n=372)

14.1 (12.8-15.4)

Chemotherapy: n=25

0.8Survival Probability

Conclusions

0.7
0.60.5

TIS + chemo(n=376)

0.4
0.3
0.2
0.1
0.0
024681012141618202224262830323436384042444648508664644754364828382430202115136103421000

HR (95% CI)a0.83 (0.70-0.97)

Time (Months)
Number of patients at risk
376 363 346 316 282 252 224 205 184 160 142 130 120 103
372 361 333 312 275 246 217 182 156 134 118 104 94 83

TIS + chemo
PBO + chemo

Data cutoff: February 28, 2023.
aHR and 95% CIs were estimated from an unstratified Cox regression model including treatment as a covariate.
Chemo, chemotherapy; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival; PBO, placebo; TIS, tislelizumab.

Methods• Of 997 randomized patients, 748 (tislelizumab with chemotherapy: n=376; placebo withchemotherapy: n=372) were enrolled from Asia, of whom 403 had a PD-L1 score of ≥5% (Figure 1)• An improvement in OS was also observed with tislelizumab plus chemotherapy versus placebo plus
chemotherapy in the PD-L1 score ≥5% population (Figure 4)
Figure 4. Overall Survival: Asian Subgroup (PD-L1 Score ≥5% Population)• The Asian subgroup comprised patients from China (including Taiwan), Japan, and South Korea
1.0Survival Probability• As of the data cutoff for the final analysis (February 28, 2023), median study follow-up in the Asiansubgroup was 14.5 months (range, 0.1-50.1) and minimum study follow-up in this subgroup was24.6 months
Figure 1. Study Design and Patient Population

0.9

Tislelizumab: n=25

0.8

Chemotherapy: n=25

0.7
0.6
0.5

TIS + chemo(n=202)0.4
0.30.2Key eligibility criteria• Locally advanced unresectable or metastatic
gastric/gastroesophageal junction histologicallyconfirmed adenocarcinoma• No HER2+ disease• No prior systemic therapy for advanced disease• At least one measurable or non-measurable
lesion (RECIST v1.1)• ECOG PS 0 or 1
Total population: N=997

Initial treatment (up to Cycle 6)

Cycle 7 and beyond

Tislelizumaba +chemotherapyb

Tislelizumaba +optional capecitabinec

1:1(n=201)

0.00

Treatment until
unacceptable toxicity or
disease progression

RPlaceboa +optional capecitabinec

Placeboa +chemotherapyb

PBO + chemo

0.1246810121416

182022242628

3032343638

404244464850

43263521311524
1319914793

7231

1000Events,n (%)

Median OS(95% CI),Monthsa

135 (66.8)

18.0 (15.0-21.6)

157 (78.1)

14.0 (12.3-15.5)

0.71 (0.56-0.89)

Time (Months)
Number of patients at risk
TIS + chemo
PBO + chemo

202 196 188 176 156 143 126 117 107 94
201 195 177 165 149 133 119 97 81 71

8660

81
51

7845

68
4356
35

Data cutoff: February 28, 2023.
aHR and 95% CIs were estimated from an unstratified Cox regression model including treatment as a covariate.
Chemo, chemotherapy; CI, confidence interval; HR, hazard ratio; OS, overall survival; PBO, placebo; PD-L1, programmed death-ligand 1; TIS, tislelizumab.

Asian patients: N=748

Endpoints• Primary endpoint: OS in PD-L1 score ≥5% and ITT populations• Secondary endpoints: Progression-free survival, objective response rate,
duration of response, and safety

Stratification factors• Regions of enrollment• Peritoneal metastasis• PD-L1 expression score (≥5% vs <5%)d• Investigator-chosen chemotherapy (XELOX or FP)• Improved PFS was observed with tislelizumab plus chemotherapy versus placebo plus
chemotherapy in the ITT and PD-L1 score ≥5% populations (Figure 5)

Tislelizumab 200 mg or placebo Q3W (day 1). bOxaliplatin 130 mg/m² IV (day 1) and oral capecitabine 1000 mg/m2 twice daily (14 consecutive days from day 1) Q3W (XELOX), or cisplatin 80 mg/m² IV(day 1) and FP 800 mg/m2/day IV (days 1-5) Q3W. cCapecitabine as maintenance therapy was optional and only for XELOX-treated patients. dPD-L1 score was determined using the VENTANA PD-L1(SP263) assay by tumor area positivity score.
ECOG PS, Eastern Cooperative Oncology Group Performance Status; FP, 5-fluorouracil; HER2, human epidermal growth factor receptor 2; ITT, intent-to-treat; IV, intravenous; OS, overall survival;
PD-L1, programmed death-ligand 1; Q3W, once every 3 weeks; R, randomized; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1.
aFigure 5. Progression-Free Survival: Asian Subgroup
PD-L1 Score ≥5% Population

ITT Population
Events,n (%)

Survival Probability• Improved OS differences of 2.1 and 4.6 months in favor of tislelizumab plus chemotherapy versus
placebo plus chemotherapy were observed in the overall ITT and PD-L1 score ≥5% populations atfinal and interim analysis, respectively (Figure 2)9Median PFS(95% CI), Months

TIS + chemo (n=376) 266 (70.7)

7.1 (5.8-8.3)

PBO + chemo (n=372) 293 (78.8)

6.9 (5.8-7.2)

0.76 (0.64-0.90)

1.0

1.0

0.9

0.9

0.8

0.8

0.70.70.6
0.5
0.4
0.3

HR (95% CI)aP Valueb370 (73.9)

15.0 (13.6-16.5)

0.80 (0.70-0.92)

PBO + chemo (n=496) 406 (81.9)

12.9 (12.1-14.1)

0.0011
1.0

0.9

0.9

0.8

0.8

0.7

0.7

Survival Probability

Survival Probability

1.0

0.6
0.5
0.4
0.3

130 (47.4)

17.2 (13.9-21.3)

0.74 (0.59-0.94)

PBO + chemo (n=272) 161 (59.2)

12.6 (12.0-14.4)

0.00560.3
0.1
0.002468

10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50

Number of patients at risk

Time (Months)

501 477 445 404 355 316 278 254 226 202 179 165 152 130 107 77496 472 431 398 344 304 264 218 186 155 136 119 109 96 73 52

02468101253294325

31202215136103421000

TIS + chemo
PBO + chemo

468Time (Months)

376 334 285 180 149 115 103 81 76
372 308 251 171 136 87 73 59 49274272262261

141618202224262830

320.40.307145653861 54
34 295125246810 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48
Time (Months)

Number of patients at risk
402137 32
16 132711211016812754423100

TIS + chemo
PBO + chemo

202 179 157 104 86 67 62 53 51 48 44 41 36 34 27 24 22 18 13 11201 167 133 91 76 46 39 30 26 23 19 17 17 15 13 10 765484423120

246
237

227
215

196
189

167
156

122
118

93
80

70
57

5244382630
161912116923000

ITT Population• Demographics and baseline characteristics of patients in the Asian subgroup were similar to those of
the overall ITT population (Table 1)

Median DoR (95% CI),
Monthsc

TIS + chemo (n=376)

51.1 (45.9-56.2)

9.5 (8.1-11.5)

PBO + chemo (n=372)

43.5 (38.4-48.8)

8.2 (6.9-9.9)

1.0

Placebo +Chemotherapy(n=372)Overall ITT Population
Tislelizumab +Chemotherapy(n=501)

Placebo +Chemotherapy(n=496)59.0 (23.0-86.0) 61.0 (25.0-83.0) 60.0 (23.0-86.0) 61.0 (25.0-86.0)

TIS + chemo (n=202)

56.9 (49.8-63.9)

10.3 (8.2-18.0)

PBO + chemo (n=201)

45.3 (38.3-52.4)

8.0 (6.5-9.9)

DoR

0.8

0.7
0.6
0.5
0.4
0.3
0.2

0.7
0.6
0.5
0.4
0.3
0.2

0.1

0.1

0.0

0.0024681012141618192 190 160 116 101 81
162 156 124 88 74 58

202224262830

32

34

36

38

40

424446Time (Months)

Number of patients at risk
TIS + chemo
PBO + chemo

Median DoR (95% CI),Monthsd

0.9DoR
Survival Probability

Asian Subgroup ITT Population

ORR %(95% CI)a,b

1.0

0.9Survival Probability

Table 1. Demographics and Baseline Disease Characteristics

PD-L1 Score ≥5% Population

ORR %(95% CI)a,b0.8

7051

65
46614258
36

5330

48
29

462341
1902468

1012

1416

1834
1730
1228
924
914
7

10
754323100

TIS + chemo
PBO + chemo

20

2224

26

28

30

32

34

36

38

40

42

44

46

25
10

22
620
4

174

93

7
34
22
12000

Time (Months)

Number of patients at risk
115 114 102 76
91 89 72 51

67
4255
30

49
2548
2444
2241
1739
15

34
1533
1131
10

Data cutoff: February 28, 2023.
aORR was calculated using the unstratified Cochran-Mantel-Haenszel method. bORR is defined as the proportion of patients with a confirmed complete response or partial response. cDoR analysis
performed on 192 patients in the TIS + chemo arm and 162 patients in the PBO + chemo arm. dDoR analysis performed on 115 patients in the TIS + chemo arm and 91 patients in the PBO + chemo arm.
Chemo, chemotherapy; DoR, duration of response; ORR, objective response rate; PBO, placebo; PD-L1, programmed death-ligand 1; TIS, tislelizumab.

258 (68.6)

261 (70.2)

346 (69.1)

346 (69.8)

0120 (31.9)

102 (27.4)

169 (33.7)

154 (31.0)

1

256 (68.1)

270 (72.6)

332 (66.3)

342 (69.0)• No new safety signals with tislelizumab plus chemotherapy were identified in the Asian subgroup(Figure 7)

Stomach329 (87.5)

319 (85.8)

405 (80.8)395 (79.6)

GEJ

47 (12.5)

52 (14.0)

96 (19.2)

100 (20.2)

Figure 7. Safety Summary: Asian Subgroup (Safety Analysis Population)

Sex, male, n (%)
ECOG PS, n (%)

Primary tumor location, n (%)a

Most Frequent Grade ≥3 TRAEs(Occurring in >5%)

PD-L1 TAP score, n (%)≥5%

202 (53.7)

201 (54.0)

274 (54.7)

272 (54.8)<5%174 (46.3)

171 (46.0)

227 (45.3)

224 (45.2)

Metastatic disease, n (%)

373 (99.2)

369 (99.2)

494 (98.6)

490 (98.8)

Peritoneal metastasis, n (%)

165 (43.9)

160 (43.0)

220 (43.9)

214 (43.1)

Investigator-chosen chemo, n (%)
Oxaliplatin/capecitabine

370 (98.4)

367 (98.7)

466 (93.0)465 (93.8)

Cisplatin/5-fluorouracil

6 (1.6)5 (1.3)35 (7.0)31 (6.3)

Data cutoff: February 28, 2023.
aThe diagnosis of 1 patient was updated from gastric adenocarcinoma to pancreatic cancer after randomization and the patient remained in the ITT population.
Chemo, chemotherapy; ECOG PS, Eastern Cooperative Oncology Group Performance Status; GEJ, gastroesophageal junction; ITT, intent-to-treat; PBO, placebo; PD-L1, programmed death-ligand 1;
TAP, tumor area positivity; TIS, tislelizumab.

References
1.

Xu et al. Ann Oncol. 2023;34(suppl 2):S1320-S1321.

2.
3.
4.
5.

Sung et al. CA Cancer J Clin. 2021;71(3):209-249.
Shin et al. Cancers (Basel). 2023;15(9):2639.
Yan et al. Chin J Cancer Res. 2023;35(2):81-91.
Sekiguchi et al. Digestion. 2022;103(1):22-28.

00Figure 6. Disease Response and Duration of Response: Asian SubgroupCox regression model was stratified by regions (east Asia vs rest of the world), PD-L1 expression, and presence of peritoneal metastasis. bP values are one-sided and based on the stratified log-rank test.
cCox regression model was stratified by regions (east Asia vs rest of the world) and presence of peritoneal metastasis.
Chemo, chemotherapy; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival; PBO, placebo; PD-L1, programmed death-ligand 1; TIS, tislelizumab.

Age, median (range), years

0.5

10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48

aTislelizumab +Chemotherapy(n=376)

0.6Time (Months)

Number of patients at risk59
390.67 (0.53-0.84)• Tislelizumab plus chemotherapy showed a favorable objective response rate and duration ofresponse compared with placebo plus chemotherapy in the ITT and PD-L1 score ≥5% populations(Figure 6)

0.4

0.2

6.8 (5.6-8.1)

Data cutoff: February 28, 2023.
aHR was based on an unstratified Cox regression model.
Chemo, chemotherapy; HR, hazard ratio; ITT, intent-to-treat; PBO, placebo; PD-L1, programmed death-ligand 1; PFS, progression-free survival; TIS, tislelizumab.

0.5

0.1
0.0

TIS + chemo
PBO + chemo

0.60.2

TIS + chemo
PBO + chemoHR (95% CI)c
P Valueb

TIS + chemo (n=274)

2

Number of patients at risk

Events,Median OSn (%) (95% CI), Monthsc

PBO + chemo (n=201) 157 (78.1)

HR (95% CI)a0.00Events,
Median OS
n (%) (95% CI), Monthsa

8.2 (6.9-9.7)

0.1

0.0

PD-L1 Score ≥5% Population at Interim Analysis9

134 (66.3)

0.2

0.1

ITT Population at Final Analysis1

Median PFS(95% CI), Months

TIS + chemo (n=202)

0.2

Figure 2. Overall Survival: Overall Population

Events,n (%)

HR (95% CI)aSurvival ProbabilityResults

TIS + chemo (n=501)

HR (95% CI)aTislelizumab +Placebo +Chemotherapy Chemotherapy(n=375)(n=370)366 (97.6)

360 (97.3)

Grade ≥3 TRAEs

208 (55.5)

185 (50.0)

Serious TRAEs

97 (25.9)55 (14.9)

Patients with at least one TRAE

TRAE leading to death

9 (2.4)3 (0.8)TRAE leading to treatment
discontinuation

64 (17.1)

33 (8.9)

TIS + chemo (n=375)

PBO + chemo (n=370)

14.9

Platelet countdecreased

14.1

Neutrophilcountdecreased

14.1

14.3

8.4

Anemia5.3
0246810121416Patients (%)
Data cutoff: February 28, 2023. Data are n (%).
Chemo, chemotherapy; PBO, placebo; TIS, tislelizumab; TRAE, treatment-related adverse event.

Presenter Disclosures
6. Cheng et al. Ther Adv Med Oncol. 2019;11:1758835919877726.
7. Lordick et al. Ann Oncol. 2022;33(10):1005-1020.
8. Catenacci et al. Oncologist. 2021;26(10):e1704-e1729.
9. Moehler et al. J Clin Oncol. 2023;41(suppl 4):286.

KK: Consultancy/advisory role for ONO Pharmaceuticals, Bristol Myers Squibb, Merck and Co, Bayer AG, AstraZeneca, BeiGene, Taiho, Merck Biopharma, Amgen, Novartis, Daiichi Sankyo;
Grant/Research funding from ONO Pharmaceuticals, Merck & Co, Bayer AG, AstraZeneca, BeiGene, Chugai, Taiho, Oncolys Biopharma, Janssen Pharmaceuticals.

Acknowledgments
We would like to thank the investigators, site support staff, and especially the patients for participating in this study. This study is sponsored by BeiGene, Ltd.
Medical writing support, under the direction of the authors, was provided by Steven Moore, PhD, and Camile Semighini Grubor, PhD, of Envision Pharma Inc.,and was funded by BeiGene.

Contact: kenkato@ncc.go.jp (Ken Kato)