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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)
Dongsheng Yue,1 Wenxiang Wang,2 Hongxu Liu,3 Qixun Chen,4 Chun Chen,5 Lunxu Liu,6Peng Zhang,7 Guofang Zhao,8 Fan Yang,9 Guang Han,10 Ying Cheng,11 Bentong Yu,12
Yue Yang,13 Haiquan Chen,14 Jie Jiang,15 Bin Yao,16 Shengfei Wang,17 Ruihua Wang,17Wenjuan Zheng,16 Changli Wang1 on behalf of the RATIONALE-315 Investigators
1Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; 2Hunan Cancer Hospital, Hunan, China;

3Liaoning Cancer Hospital and Institute, Shenyang, China; 4Zhejiang Cancer Hospital, Hangzhou, China; 5Fujian
Medical University Union Hospital, Fuzhou, China; 6West China Hospital, Sichuan University, Chengdu, China;
7Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; 8Ningbo No.2 Hospital, Ningbo,
China; 9Peking University People’s Hospital, Beijing, China; 10Hubei Cancer Hospital, Wuhan, China; 11Jilin Cancer
Hospital, Changchun, China; 12The First Affiliated Hospital of Nanchang University, Nanchang, China; 13Beijing Cancer
Hospital, Beijing, China; 14Fudan University Shanghai Cancer Center, Shanghai, China; 15The First Affiliated Hospitalof Xiamen University, Xiamen, China; 16BeiGene (Beijing) Co., Ltd, Beijing, China; 17BeiGene (Shanghai) Co., Ltd,
Shanghai, China

Declaration of Interests
Dongsheng Yue
Dongsheng Yue reports no conflicts of interest

Dongsheng Yue

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Background••

Surgery offers the highest likelihood of cure for patients with resectable, early-stage NSCLC; however, the5-year tumour recurrence rate can be as high as 67% (depending on disease stage)1-5
In recent years, management of resectable NSCLC has evolved rapidly with emerging evidence of clinicalbenefit for perioperative anti-PD-(L)1 mAb treatment in combination with neoadjuvant CT6-10
RATIONALE-315 (NCT04379635) is investigating the efficacy and safety of
perioperative TIS (anti-PD-1 mAb) or PBO plus neoadjuvant PtDb CT inpatients with resectable stage II-IIIA NSCLC in China
Here, we present the interim results for EFS and OS

Abbreviations: CT, chemotherapy; EFS, event-free survival; mAb, monoclonal antibody; NSCLC, non-small cell lung cancer; OS, overall survival; PBO, placebo; PD-1, programmed-death 1; PD-L1, programmed death-ligand 1; PtDb, platinum-based doublet; TIS, tislelizumab.
1. Uramoto H and Tanaka F. Transl Lung Cancer Res. 2014;3:242-249. 2. Kelsey CR, et al. Cancer. 2009;115:5218-5227. 3. Gourcerol D, et al. Eur Respir J. 2013;42:1357-1364. 4. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Non-Small Cell Lung Cancer: Version 5 2023.
nscl.pdf (nccn.org). 5. West H, et al. Clin Lung Cancer. 2023;24:260-268. 6. Forde PM, et al. N Engl J Med. 2022;386:1973-1985. 7. Felip E, et al. Lancet. 2021;398:1344-1357. 8. O’Brien M, et al. Lancet Oncol. 2022;23:1274-1286. 9. Wakelee H, et al. N Engl J Med. 2023;389:491-503.
10. Heymach JV, et al. N Engl J Med. 2023;389:1672-1684.

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RATIONALE-315 Study Design
Neoadjuvant phase(3-4 cycles)
Key eligibility criteria

Dongsheng
YueII-IIIA NSCLC• Resectable stage

per AJCC 8th edition (eligible forR0 resection)• ECOG PS 0 or 1
• EGFR/ALK WTa
Stratification• Histology (squamous vsnon-squamous)• Disease stage (II vs IIIA)• PD-L1 expression (≥1% vs<1%/not evaluable/indeterminate)

TIS Arm

Surgery

Adjuvant phase(up to 8 cyclesb)

TIS(200 mg IV Q3W)
+ PtDb CT

Surgery

TIS(400 mg IV Q6W)

PBO (IV Q3W)
+ PtDb CT

SurgeryPBO(IV Q6W)R
1:1

PBO Arm

Primary endpoints:• MPR rate by BIPR and
EFS by BICR
Key secondary endpoint:• pCR rate by BIPR
Other secondary
endpoints:• OS, EFS by investigator,
safety (and others notreported here)

PtDb CT• Squamous: cisplatin/carboplatin + paclitaxel• Non-squamous: cisplatin/carboplatin + pemetrexed

Data cut-off: August 21, 2023 (median study follow-up: 22.0 months [range: 0.1, 38.4]).
ClinicalTrials.gov Identifier: NCT04379635.
a EGFR testing was mandatory for non-squamous NSCLC. b Adjuvant treatment was only received by patients with an ECOG PS of 0 or 1 and adequate organ function for ≤8 cycles or until disease recurrence/progression, unacceptable adverse events, or death occurs, or if the patient and/or
investigator decided to discontinue study treatment.
Abbreviations: AJCC, American Joint Committee on Cancer; ALK, anaplastic large-cell lymphoma kinase; BICR, blinded independent central review; BIPR, blinded independent pathology review; ECOG PS, Eastern Cooperative Oncology Group performance status; EFS, event-free survival;
EGFR, epidermal growth factor receptor; IV, intravenously; MPR, major pathological response; NSCLC, non-small cell lung cancer; OS, overall survival; PBO, placebo; pCR, pathological complete response; PD-L1, programmed death-ligand 1; PtDb CT, platinum-based doublet chemotherapy;
Q3W, once every 3 weeks; Q6W, once every 6 weeks; R, randomised; R0, pathological complete resection of the primary tumour; TIS, tislelizumab; WT, wild-type.

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Statistical Considerations•••

Overall type I error was strongly controlled at a
one-sided alpha of 0.025
The interim analysis for EFS was planned forwhen ~75% of the targeted EFS events (184
EFS events) had occurred, with Lan-DeMets
alpha spending function approximation to theO’Brien–Fleming boundary
The OS interim analysis was to be tested with
Haybittle–Peto P-value boundary at 0.0001 at
this interim analysis

Type I Error Control Scheme
One-sided α = 0.025
α = 0.005
α = 0.02
MPR of TIS vs PBO
α = 0.005

If pCR is positive, α = 0.005
EFS of TIS vs PBO

pCR of TIS vs PBO
If EFS is positive, α = 0.02
If MPR, pCR, and EFS are positive, α = 0.025
OS of TIS vs PBO

Abbreviations: EFS, event-free survival; MPR, major pathological response; OS, overall survival; PBO, placebo; pCR, pathological complete response; TIS, tislelizumab.

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Patient Disposition (ITT Analysis Set)
N=453 patients randomised

15 (6.6%) discontinued
neoadjuvant txa

Adverse event
Patient withdrawal
Progressive disease
Physician decision

7 (3.1%)5 (2.2%)2 (0.9%)1 (0.4%)36 (15.9%) had surgery cancelleda
Patient withdrawal
Progressive disease
Adverse event
Physician decision
Otherb20 (8.8%)
6 (2.7%)6 (2.7%)3 (1.3%)1 (0.4%)22 (9.7%) did not receive
adjuvant txa

Patient withdrawal
Adverse event
Physician decision
Progressive disease

10 (4.4%)
7 (3.1%)4 (1.8%)1 (0.4%)51 (22.6%) discontinued
adjuvant txa

Progressive disease
Adverse event
Patient withdrawal
Physician decision

20 (8.8%)
15 (6.6%)9 (4.0%)7 (3.1%)Adverse event
Patient withdrawal
Progressive disease
Physician decision

2 (0.9%)9 (4.0%)4 (1.8%)2 (0.9%)TIS arm N=226

PBO arm N=227

226 (100.0%) received neoadjuvant txa

226 (99.6%) received neoadjuvant txa

211 (93.4%) completed neoadjuvant txa

210 (92.5%) completed neoadjuvant txa

54 (23.8%) had surgery cancelleda

190 (84.1%) received definitive surgerya

173 (76.2%) received definitive surgerya

26 (11.5%) did not receive
adjuvant txa••

130 (57.5%) received 3 cycles of TIS
78 (34.5%) received 4 cycles of TIS

168 (74.3%) received adjuvant TISa
106 (46.9%) completed adjuvant txa
11 (4.9%) adjuvant TIS ongoing••

118 (52.2%) received 3 cycles of PBO
91 (40.3%) received 4 cycles of PBO

147 (64.8%) received adjuvant PBOa
101 (44.5%) completed adjuvant PBOa
8 (3.5%) adjuvant PBO ongoing

Data cut-off: August 21, 2023
Median study follow-up: 22.0 months (range: 0.1, 38.4)

The ITT analysis set included all randomised patients. a Denominator based on randomised patients. b Patient was reported to cancel surgery due to lost to follow-up.
Abbreviations: ITT, intention-to-treat; PBO, placebo; TIS, tislelizumab; tx, treatment.

Dongsheng Yue

17 (7.5%) discontinued
neoadjuvant txa

Patient withdrawal
Progressive disease
Adverse event
Physician decision

Patient withdrawal
Adverse event
Physician decision
Progressive disease

28 (12.3%)
17 (7.5%)
2 (0.9%)7 (3.1%)13 (5.7%)
4 (1.8%)7 (3.1%)2 (0.9%)38 (16.7%) discontinued
adjuvant txa

Progressive disease
Adverse event
Patient withdrawal

32 (14.1%)
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Demographics and Baseline Characteristics
ITT Analysis Set
Age, median (IQR), years
Male sex, n (%)
Asian race, n (%)
ECOG PS, n (%)a0
1
Smoking status, n (%)
Current/former
Never
Histology, n (%)b
Squamous
Non-squamous
Disease stage, n (%)
II
IIIA
cN status, n (%)cN0
N1
N2
PD-L1 expression, n (%)d<1%≥1%Not evaluable/indeterminate

Dongsheng Yue

TIS arm (N=226)
62.0 (57.0, 67.0)
205 (90.7)
226 (100.0)

PBO arm (N=227)
63.0 (56.0, 68.0)
205 (90.3)
227 (100.0)

142 (62.8)
83 (36.7)

154 (67.8)
73 (32.2)

193 (85.4)
33 (14.6)

190 (83.7)
37 (16.3)

179 (79.2)
45 (19.9)

175 (77.1)
50 (22.0)

92 (40.7)
132 (58.4)

91 (40.1)
133 (58.6)

60 (26.5)
84 (37.2)
82 (36.3)

54 (23.8)
93 (41)79 (34.8)

89 (39.4)
130 (57.5)
7 (3.1)84 (37.0)
132 (58.1)
11 (4.8)

a One patient in the TIS arm had a missing ECOG PS. b Histology by CRF; patients with mixed histology were categorised as ‘Other’ (n=2 [0.9%] in each arm). c One patient was enrolled (PBO arm) with N3. d PD-L1 expression from Central Lab.
Abbreviations: cN, clinical N; CRF, case report form; ECOG PS, Eastern Cooperative Oncology Group performance status; IQR, interquartile range; ITT, intention-to-treat; PBO, placebo; PD-L1, programmed death-ligand 1; TIS, tislelizumab.

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Major Pathological and Pathological Complete Responses
Per BIPR (ITT Analysis Set)
70

MPRa
Difference=41.1% (95% CI: 33.2, 49.1); P<0.0001

70
60

50

pCR rate (%)

MPR rate (%)

60

40
30

56.2%

10

•

50
40
30
20

20

0

pCRb
Difference=35.0% (95% CI: 27.9, 42.1); P<0.0001

15.0%
TIS arm(N=226)

PBO arm(N=227)

40.7%

10
0

5.7%
TIS arm(N=226)

PBO Arm(N=227)

Neoadjuvant TIS + PtDb CT showed a statistically significant and clinically meaningful improvement in MPR and pCR rates
vs neoadjuvant PBO + PtDb CT

Final MPR and pCR analysis at the February 20, 2023, cut-off. Patients who did not receive surgical resection were considered non-responders. a MPR was defined as the proportion of patients with ≤10% residual viable tumour in the resected primary tumour and resected lymph nodes after
completion. b pCR was defined as the proportion of patients absent of residual viable tumour in the resected primary tumour and resected lymph nodes after treatment.
Abbreviations: BIPR, blinded independent pathology review; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; ITT, intention-to-treat; MPR, major pathological response; NSCLC, non-small cell lung cancer; OR, odds ratio; PBO, placebo;
pCR, pathological complete response; PD-L1, programmed death-ligand 1; PtDb CT, platinum-based doublet chemotherapy; TIS, tislelizumab.
Yue D, et al. Presented at ESMO, Madrid, Spain; October 23, 2023.

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Event-Free Survival

EFS (%)Per BICR (ITT Analysis Set)

Number at risk:
TIS arm
PBO arm

•
•

100
90
80
70
60
50
40
30
20
10
0

Events (%)
TIS arm 58 (25.7)
PBO arm 83 (36.6)

Median (95% CI), months
HR (95% CI)
NR (NE, NE)
0.56 (0.40, 0.79)
NR (16.6, NE)

P-value
0.0003

TIS arm
PBO arm

80.0%
68.3%
68.1%

0

3

6

9

12

226
227

196
187

176
149

160
129

146
113

51.8%

15

18

21

24

27

30

33

36

39

127
95

105
77

84
57

67
42

37
24

35
23

10
4

3
2

0
0

Time from randomisation (months)

A statistically significant and clinically meaningful improvement in EFS (HR=0.56 [95% CI: 0.40, 0.79]; one-sided
P=0.0003) was observed favouring perioperative TIS

A clinically meaningful improvement in EFS per investigator (HR=0.55 [95% CI: 0.39, 0.77]) was also observed

Analysis occurred at the August 21, 2023, cut-off. EFS was defined as the time from randomisation until any of the following, whichever occurred first: disease progression precluding surgery, local or distant recurrence, or death due to any cause. The significance boundary of the EFS interim
analysis was 0.0105 (calculated based on 141 actual EFS events).
Abbreviations: CI, confidence interval; BICR, blinded independent central review; EFS, event-free survival; HR, hazard ratio; ITT, intention-to-treat; NE, not evaluable; NR, not reached; PBO, placebo; TIS, tislelizumab.

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Event-Free Survival By Subgroups
ITT Analysis Set
Subgroup

TIS arm, n/N

PBO arm, n/N

OverallAge group<65 years≥65 years
Sex
Male
Female
ECOG performance status01
Disease stage at baseline
II
IIIA
Histologic type of tumour
Squamous
Non-squamous
PD-L1 expression<1% [excluding not evaluable/indeterminate]
≥1%
1-49%
≥50%
Smoking status
Current
FormerNever

58/22683/227

HR (95% CI)

0.57 (0.41, 0.80)

38/143
20/83

47/12936/98

0.61 (0.40, 0.94)
0.51 (0.30, 0.89)

53/205
5/21

78/2055/22

0.57 (0.40, 0.80)
0.68 (0.19, 2.40)

35/142
23/83

54/15429/73

0.57 (0.37, 0.87)
0.58 (0.33, 1.00)

16/92
42/132

29/91
54/1330.47 (0.26, 0.87)
0.62 (0.42, 0.94)

43/17915/45

63/17519/50

0.56 (0.38, 0.83)
0.64 (0.32, 1.26)

26/89
31/130
12/59
19/71

27/84
51/13231/70
20/62

0.80 (0.47, 1.38)
0.50 (0.32, 0.78)
0.34 (0.17, 0.66)
0.71 (0.38, 1.34)

10/43
40/1508/33

16/52
56/13811/37

0.61 (0.28, 1.34)
0.54 (0.36, 0.81)
0.60 (0.24, 1.51)
0

TIS arm1

HR (95% CI)

2

PBO arm

EFS was defined as the time from randomisation until any of the following, whichever occurred first: disease progression precluding surgery, local or distant recurrence, or death due to any cause.
Abbreviations: CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; EFS, event-free survival; HR, hazard ratio; ITT, intention-to-treat; PD-L1, programmed death-ligand 1; TIS, tislelizumab.

Dongsheng Yue

The EFS benefit withperioperative TIS overPBO was generally
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Event-Free Survival By Histology
ITT Analysis Set
Squamous

90

79.8%

80

EFS (%)

60

70.5%

50

20

TIS arm
PBO arm

100Median (95% CI),monthsEvents (%)

03

43 (24.0)
63 (36.0)

69

NR (NE, NE)
NR (16.6, NE)

12

15

18

21

24

80
61

65
45

53
33

50

0.56 (0.38, 0.83)

29
18

27
17

61.4%

40
20

30

60.8%

60

30

27

TIS arm
PBO arm

80.3%

80

HR (95% CI)

TIS arm
PBO arm

10
33

36

39

Time from randomisation (months)

Number at risk:
TIS arm 179 154 135 122 112 99
PBO arm 175 143 114 101 92 75

90
70

52.2%

40
30

TIS arm
PBO arm70.2%

70Non-squamous100

EFS (%)

100

8
4

3
2

0
0

0

0

Number at risk:
TIS arm 45
PBO arm 50

3

6

52.1%

Events (%)

Median (95% CI),months15 (33.3)
19 (38.0)

NR (19.1, NE)
NR (11.1, NE)

9

12

15

18

21

HR (95% CI)
0.64 (0.32, 1.26)

24

27

30

33

36

39

8
6

2
0

0
0

0
0

Time from randomisation (months)

40
43

39
35

36
28

32
21

27
20

24
16

18
12

13
9

8
6

The EFS improvement with perioperative TIS over PBO was consistently observed in patientswith squamous and non-squamous NSCLCEFS was defined as the time from randomisation until any of the following, whichever occurred first: disease progression precluding surgery, local or distant recurrence, or death due to any cause.
Abbreviations: CI, confidence interval; EFS, event-free survival; HR, hazard ratio; ITT, intention-to-treat; NE, not evaluable; NR, not reached; NSCLC, non-small cell lung cancer; PBO, placebo; TIS, tislelizumab.

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Event-Free Survival By Disease StageITT Analysis Set
aStage II

100

85.2%

90

TIS arm
PBO arm

75.7%

80

90

63.3%

70

60

74.2%

50

56.2%

40
30

Median (95% CI),monthsEvents (%)

20

TIS arm
PBO arm

100

Number at risk:
TIS arm 92
PBO arm 91

3

16 (17.4)
29 (31.9)69

NR (NE, NE)
NR (16.6, NE)

1215EFS (%)EFS (%)

TIS arm
PBO arm

76.5%

80

70

0

Stage IIIA

100

18

21

24

68
61

63
54

58
47

48
39

41
30

30
21

22
13

50

HR (95% CI)
0.47 (0.26, 0.87)

20

27

30

14
7

13
7

63.8%

40
30
TIS arm
PBO arm

10
33

36

39

Time from randomisation (months)

77
78

60

8
2

2
2

0
0

0

0

3

6

48.5%

Events (%)

Median (95% CI),months42 (31.8)
54 (40.6)

NR (29.6, NE)
19.8 (13.1, NE)

9

Number at risk:
TIS arm 132 117 106 95
PBO arm 133 107 87 74

12

15

18

21

HR (95% CI)
0.62 (0.42, 0.94)

24

27

30

33

36

39

20
16

1
2

0
0

0
0

Time from randomisation (months)

86
65

77
55

62
47

52
36

43
29

21
17

The EFS benefit with perioperative TIS over PBO was confirmed in patients with stage II and IIIA NSCLCa Stage IIA, IIB: 6.2% and 34.5% in TIS arm, 4.8% and 35.2% in PBO arm. EFS was defined as the time from randomisation until any of the following, whichever occurred first: disease progression precluding surgery, local or distant recurrence, or death due to any cause.

Abbreviations: CI, confidence interval; EFS, event-free survival; HR, hazard ratio; ITT, intention-to-treat; NE, not evaluable; NR, not reached; NSCLC, non-small cell lung cancer; PBO, placebo; TIS, tislelizumab..

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Overall Survival

OS (%)ITT Analysis Set

Number at risk:
TIS arm
PBO arm

100
90
80
70
60
50
40
30
20
10
0

Events (%)

Median (95% CI), months

HR (95% CI)

P-value

TIS arm

31 (13.7)

NR (NE, NE)

0.62 (0.39, 0.98)

0.0193

PBO arm45 (19.8)

NR (35.0, NE)

94.5%
90.9%

0

3

6

9

12

226
227

218
214

211
207

208
199

204
182

TIS arm
PBO arm

88.6%
79.4%

15

18

21

24

27

30

33

36

39

184
157

160
136

131
112

103
84

72
55

47
40

35
26

11
7

0
0

Time from randomisation (months)

An OS benefit trend (HR=0.62 [95% CI: 0.39, 0.98]; one-sided P=0.0193) was observed favouring perioperative TIS
OS was defined as the time from the date of randomisation to the date of death due to any cause.
Abbreviations: CI, confidence interval; HR, hazard ratio; ITT, intention-to-treat; NE, not evaluable; NR, not reached; OS, overall survival; PBO, placebo; TIS, tislelizumab.

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Safety Summary
Safety Analysis Set
n (%)
Dongsheng
Yue

Patients with ≥1 TRAE
Grade ≥3
Serious
Leading to deatha
Leading to discontinuation
Leading to dose modificationb
Leading to surgery delayc
Leading to surgery cancellation
Patients with ≥1 immune-mediated AE
Grade ≥3
Serious
Leading to death
Leading to discontinuation
Leading to dose modification

TIS arm (N=226)

PBO arm (N=226)

224 (99.1)
163 (72.1)
35 (15.5)
4 (1.8)29 (12.8)
88 (38.9)
12 (5.3)
1 (0.4)90 (39.8)
21 (9.3)
23 (10.2)
2 (0.9)d15 (6.6)30 (13.3)

225 (99.6)
150 (66.4)
18 (8.0)
2 (0.9)21 (9.3)
73 (32.3)
4 (1.8)1 (0.4)40 (17.7)
6 (2.7)5 (2.2)00
6 (2.7)The safety profile in the TIS arm was manageable and consistent with the known risks of the individual therapies
a TIS arm (n=1 each): infection, pneumonia, pneumonitis, immune-mediated lung disease. PBO arm: respiratory haemorrhage, cardiac failure. b Including temporary discontinuation of TIS/PBO in neoadjuvant phase, chemotherapy dose reduction, dose interruption, dose delay, and infusion rate

decrease. c Defined as when date of surgery is beyond 6 weeks after last neoadjuvant treatment dose. d (n=1 each): pneumonitis, immune-mediated lung disease.
The safety analysis set included all randomised patients who received ≥1 dose of any study drug. AEs were classified based on MedDRA v26.0. AEs were graded for severity using Common Terminology Criteria for AEs v5.0.
Abbreviations: AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; PBO, placebo; TIS, tislelizumab; TRAE, treatment-related adverse event.

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Most Frequently Reported TRAEs≥20% of Patients; Safety Analysis Set
Dongsheng
Yue
n (%)

TIS arm (N=226)

Grade ≥3
138 (61.1)

Any grade
176 (77.9)

PBO arm (N=226)

Neutrophil count decreased

Any grade177 (78.3)

Grade ≥3
134 (59.3)

White blood cell count decreased

143 (63.3)

38 (16.8)

152 (67.3)

32 (14.2)

Alopecia106 (46.9)

1 (0.4)118 (52.2)

1 (0.4)

Anaemia

91 (40.3)

11 (4.9)

96 (42.5)

15 (6.6)

ALT increased

65 (28.8)

2 (0.9)48 (21.2)

1 (0.4)

Nausea60 (26.5)

1 (0.4)59 (26.1)

0 (0.0)AST increased

53 (23.5)

2 (0.9)38 (16.8)

0 (0.0)

Platelet count decreased

47 (20.8)

5 (2.2)49 (21.7)

6 (2.7)

Hypoaesthesia

44 (19.5)

0 (0.0)47 (20.8)

0 (0.0)Decreased appetite

40 (17.7)

1 (0.4)47 (20.8)

0 (0.0)The most frequently reported TRAEs were neutrophil count decreased, white blood cell count decreased,
and alopecia; no new safety signals were identified
AEs were classified based on MedDRA v26.0 and were graded for severity using Common Terminology Criteria for Adverse Events v5.0.
Abbreviations: AE, adverse event; ALT, alanine transaminase; AST, aspartate transaminase; MedDRA, Medical Dictionary for Regulatory Activities; PBO, placebo; TIS, tislelizumab; TRAE, treatment-related adverse event.

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Most Frequently Reported Immune-Mediated AEs≥1% of Patients; Safety Analysis Set
Dongsheng
Yue
n (%)

Any grade

Immune-mediated skin adverse reaction

TIS arm (N=226)

PBO arm (N=226)

Grade ≥3

Any grade

Grade ≥3

39 (17.3)

5 (2.2)24 (10.6)

0 (0.0)Immune-mediated pneumonitis

18 (8.0)

7 (3.1)4 (1.8)0 (0.0)Immune-mediated hepatitis

5 (2.2)4 (1.8)5 (2.2)5 (2.2)

Hypothyroidism

33 (14.6)

2 (0.9)6 (2.7)0 (0.0)Hyperthyroidism

16 (7.1)

1 (0.4)7 (3.1)0 (0.0)Thyroiditis

5 (2.2)0 (0.0)0 (0.0)0 (0.0)Adrenal insufficiency

3 (1.3)1 (0.4)0 (0.0)0 (0.0)Immune-mediated endocrinopathies

The most common immune-mediated AE category was skin adverse reaction,with <10% of patients experiencing grade ≥3 immune-mediated AEs
AEs were classified based on MedDRA v26.0 and were graded for severity using Common Terminology Criteria for Adverse Events v5.0.
Abbreviations: AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; PBO, placebo; TIS, tislelizumab.

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Conclusions•

RATIONALE-315 demonstrated a clinically meaningful and statistically significant benefit in EFS with perioperative TIS plus
neoadjuvant PtDb CT vs PBO plus neoadjuvant PtDb CT at this interim analysis:•

HR=0.56 (95% CI: 0.40, 0.79); one-sided P=0.0003•

EFS benefit was generally consistent across predefined subgroups•

MPR and pCR rates were significantly improved with neoadjuvant TIS plus PtDb CT vs PBO plus PtDb CT: 56.2% vs 15.0%(P<0.0001) and 40.7% vs 5.7% (P<0.0001), respectively•

An OS benefit trend favouring perioperative TIS (HR=0.62 [95% CI: 0.39, 0.98]; one-sided P=0.0193) was observed at thisinterim analysis. The trial will continue to assess OS with longer follow-up•

The safety profile of perioperative TIS plus neoadjuvant PtDb CT was manageable and consistent with the known risks of theindividual therapies•

Taken together, the statistically and clinically significant EFS, MPR, and pCR benefits, alongside manageable safety, support
the use of perioperative TIS plus neoadjuvant PtDb CT for patients with resectable stage II-IIIA NSCLC

Abbreviations: CI, confidence interval; EFS, event-free survival; HR, hazard ratio; MPR, major pathological response; NSCLC, non-small cell lung cancer; OS, overall survival; PBO, placebo; pCR, pathological complete response; PtDb CT, platinum-based doublet chemotherapy; TIS, tislelizumab.
Yue D, et al. Annal Oncol. 2023;34(Suppl 2):S1299.

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Acknowledgements•

The authors would like to thank the patients, caregivers, and family members who participated in this study•

We would like to acknowledge all of the investigators who have contributed to the RATIONALE-315 study: Lejie Cao, Chun Chen,
Qixun Chen, Haiquan Chen, Yuping Chen, Jun Chen, Fang Chen, Ying Cheng, Jiuwei Cui, Junke Fu, Guang Han, Jian Hu, Mu Hu,
Yunchao Huang, Jie Jiang, Shanqing Li, Lin Li, Qiang Li, Jun Li, Yongde Liao, Lunxu Liu, Hongxu Liu, Changhong Liu, Naiquan Mao,
Tiejun Ren, Yuping Sun, Lijie Tan, Min Tao, Yongsheng Wang, Changli Wang, Wenxiang Wang, Ming Wu, Jun Wu, Jianping Xiong,
Shidong Xu, Yue Yang, Fan Yang, Kunpeng Yang, Min Ye, Bentong Yu, Lanjun Zhang, Peng Zhang, Qiudi Zhang, Lumin Zhang, Yi
Zhang, Jian Zhao, Guofang Zhao, Hua Zhong, Kunshou Zhu, and Xibin Zhuang•This study was sponsored by BeiGene, Ltd.

•

Medical writing support, under the direction of the authors, was provided by Russ Craddock, PhD, of Parexel, and was funded by
BeiGene, Ltd.
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Dongsheng Yue

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