Efficacy and Safety of Sitravatinib Plus Tislelizumab or Placebo Plus Tislelizumab Versus Placebo as Adjuvant Treatment in Participants With Hepatocellular Carcinoma

• Sponsor: BeiGene (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05564338
• Collaborator: (none)
• Enrollment: 684
• Locations: 82
• Arms: 4
• Anticipated Duration (Months): 58
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy and safety of sitravatinib plus tislelizumab or placebo plus tislelizumab versus placebo. The study will also compare the recurrence-free survival (RFS) in participants with hepatocellular carcinoma (HCC) who are at high risk of recurrence after surgical resection.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Sitravatinib; Drug: Tislelizumab; Drug: sitravatinib-matching placebo; Drug: tislelizumab-matching placebo	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 684 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Compare the Efficacy and Safety of Sitravatinib Plus Tislelizumab or Placebo Plus Tislelizumab Versus Placebo as Adjuvant Treatment in Patients With Hepatocellular Carcinoma Who Are at High Risk of Recurrence After Surgical Resection
• Anticipated Study Start Date: Jun 30, 2023
• Anticipated Primary Completion Date: Apr 30, 2027
• Anticipated Study Completion Date: Apr 30, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm A: sitravatinib + tislelizumab sitravatinib once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)	Drug: Sitravatinib; Administered orally; Drug: Tislelizumab; Administered intravenously
Experimental: Treatment Arm B: Placebo + tislelizumab sitravatinib-matching placebo once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)	Drug: Tislelizumab; Administered intravenously; Drug: sitravatinib-matching placebo; administered orally
Experimental: Treatment Arm C:Sitravatinib + Placebo sitravatinib once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)	Drug: Sitravatinib; Administered orally; Drug: tislelizumab-matching placebo; administered intravenously
Experimental: Treatment Arm D: Matching Placebo sitravatinib-matching placebo once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)	Drug: sitravatinib-matching placebo; administered orally; Drug: tislelizumab-matching placebo; administered intravenously

Outcome Measures

Primary Outcome Measures

1. Recurrence-free survival (RFS) as assessed by the investigator between Arm A and Arm D [Up to 2 Years]

   RFS is defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma (HCC) as assessed by the investigator, or death from any cause, whichever occurs first.

2. Recurrence-free survival (RFS) as assessed by the investigator between Arm B and Arm D [Up to 2 Years]

   defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first.

Secondary Outcome Measures

1. Arm A and Arm B: Recurrence-free survival (RFS) [Up to 2 Years]

   defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first.

2. Arm A and Arm C: Recurrence-free survival (RFS) [Up to 2 Years]

   defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first.

3. Arm A and Arm D: overall survival (OS) [Up to 5 Years]

   defined as the time from the date of randomization until the date of death due to any cause

4. Arm B and Arm D: overall survival (OS) [Up to 5 Years]

   defined as the time from the date of randomization until the date of death due to any cause

5. Arm A and Arm B: overall survival (OS) [Up to 5 Years]

   defined as the time from the date of randomization until the date of death due to any cause

6. Arm A and Arm C: overall survival (OS) [Up to 5 Years]

   defined as the time from the date of randomization until the date of death due to any cause

7. Arm A and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator [Up to 2 Years]

   defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC

8. Arm B and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator [Up to 2 Years]

   defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC

9. Arm A and Arm B: time to extrahepatic spread (EHS) as assessed by the investigator [Up to 2 Years]

   defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC

10. Arm A and Arm C: time to extrahepatic spread (EHS) as assessed by the investigator [Up to 2 Years]

    defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC

11. Number of participants with adverse events (AEs) [Up to 5 Years]

    Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0, vital signs, and clinical laboratory test results in the Safety Analysis Set

12. Participants Reported Outcome as measured at Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and its hepatocellular carcinoma cancer module QLQ-HCC18 [Up to 2 Years]

    Quality of Life change with treatment. Scale scores are calculated by averaging items within scales and transforming average scores linearly. All of the scales range in score from 0 to 100

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Participant with a first diagnosis of HCC must have undergone a curative-intent resection within 4 to 12 weeks before randomization and have a documented histological confirmation of HCC diagnosis and negative surgical margins (R0 resection) of the resected tumor

2. Participant must have tumor-free status as assessed by the investigator and have fully recovered from surgical resection before randomization

3. Participant must have no extrahepatic HCC

4. ECOG Performance Status ≤ 1

5. Participant who has undergone surgical resection and is defined as having a high risk of HCC recurrence

Key Exclusion Criteria:

1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology

2. Evidence of residual, recurrent, or metastatic disease of HCC before randomization

3. Major macrovascular (gross vascular) invasion of the portal vein (Vp3 or Vp4) or any grade of macrovascular invasion in the hepatic vein or inferior vena cava

4. Untreated chronic hepatitis B (HBV) or chronic HBV carriers with HBV DNA ≥ 2000 IU/mL at Screening

5. Untreated or incompletely treated esophageal or gastric varices with bleeding or high risk of bleeding

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui	China	233004
2	Beijing Cancer Hospital	Beijing	Beijing	China	100142
3	Peking Union Medical College Hospital - Oncology	Beijing	Beijing	China	100730
4	Cancer Hospital Chinese Academy of Medical Sciences City: Beijing	Beijing	Beijing	China
5	Peking University Third Hospital	Beijing	Beijing	China
6	Daping Hospital, Third Military Medical University	Chongqing	Chongqing	China	400042
7	Fujian Cancer Hospital	Fuzhou	Fujian	China	350014
8	Zhongshan Hospital,Fudan University (Xiamen Branch）	Xiamen	Fujian	China	361006
9	Mengchao Hepatobiliary Hospital of Fujian Medical University	Gulou	Fuzhou	China
10	The First Hospital of Lanzhou University	Lanzhou	Gansu	China	73000
11	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong	China	510000
12	Sun Yat-Sen University Cancer Center (Huangpu Campus)	Guangzhou	Guangdong	China	510060
13	Guangdong Provincial People's Hospital	Guangzhou	Guangdong	China	510080
14	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University	Guangzhou	Guangdong	China	510120
15	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong	China	510515
16	Sun yat-sen memorial hospital, sun yat-sen university (south)	Guanzhou	Guangdong	China	510275
17	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi	China	530021
18	Guizhou Cancer Hospital	Guiyang	Guizhou	China	550000
19	Hainan General Hospital - Oncology	Haikou	Hainan	China
20	Second Affiliated Hospital of Zhejiang University School of Medicine	Zhejiang	Hangzhou	China	310009
21	Harbin Medical University Cancer Hospital - Oncology	Haerbin	Heilongjiang	China	150081
22	Hubei Cancer Hospital - Oncology	Wuhan	Hubei	China	400037
23	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei	China
24	Hunan Cancer Hospital	Changsha	Hunan	China	410013
25	The First People's Hospital of Changzhou - Oncology	Changzhou	Jiangsu	China	213003
26	Nantong Tumor Hospital	Nantong	Jiangsu	China	226000
27	Affiliated hospital of Nantong university	Nantong	Jiangsu	China	226001
28	Northern Jiangsu people's hospital - Oncology	Yangzhou	Jiangsu	China	225001
29	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	330006
30	Jiangxi Province Cancer Hospital	Nanchang	Jiangxi	China	330039
31	The First Hospital of China Medical University	Shenyang	Liaoning	China	110001
32	Liaoning Cancer Hospital & Institute - Medical Oncology - Oncology	Shenyang	Liaoning	China	110017
33	Shengjing Hospital of China Medical University	Shenyang	Liaoning	China	110022
34	The Second Affiliated Hospital of Fujian Medical University	Fujian	Quanzhou	China	362001
35	Shandong Cancer Hospital - oncology - Oncology	Jinan	Shandong	China
36	The Affiliated Hospital of Qingdao University Branch South	Qingdao	Shandong	China	266000
37	Affiliated Zhongshan Hospital of Fudan University	Shanghai	Shanghai	China	200032
38	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi	China	030013
39	Sichuan Cancer Hospital & Institute	Chengdu	Sichuan	China	610041
40	West China Hospital, Sichuan University	Chengdu	Sichuan	China	610041
41	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin	China
42	Affiliated Cancer Hospital of Xinjiang Medical University	Ürümqi	Xinjiang	China
43	The First Affiliated Hospital of Xinjiang Medical University	Ürümqi	Xinjiang	China
44	Yunnan Cancer Hospital - Oncology	Kunming	Yunnan	China	650100
45	Yunnan Cancer Hospital, &The Third Affiliated Hospital of Kunming Medical University&Yunnan Cancer Center &Yunnan Cancer Center	Kunming	Yunnan	China	650118
46	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang	China
47	Taizhou Hospital of Zhejiang Province	Taizhou	Zhejiang	China	317000
48	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang	China
49	The First Affiliated Hospital of Chongqing Medical University	Chongqing		China
50	Zhongshan Hospital Xiamen University	Fujian		China
51	Anhui Provincial Hospital - Oncology	Hefei		China	230001
52	Linyi Cancer Hospital	Shandong		China
53	Tongji Hospital of Tongji Medical College Huazhong University of Science Technology	Wuhan		China	Hubei
54	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an		China	710061
55	The Catholic University of Korea, Bucheon St. Mary's Hospital	Gyeonggi-do	Bucheon-si	Korea, Republic of	14647
56	Kyungpook National University Hospital	Daegu	Chungcheongnam-do	Korea, Republic of
57	National Cancer Center (NCC)	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
58	Chonnam National University Hwasun Hospital - Hematology and Oncology Clinic	Hwasun	Jeonranamdo [Chollanam-do]	Korea, Republic of	58128
59	Samsung Medical Center - Hematology-Oncology	Seoul	Seoul Teugbyeolsi [Seoul-T'ukp	Korea, Republic of	06351
60	Korea University Guro Hospital - Hematology-Oncology	Seoul	Seoul Teugbyeolsi [Seoul-T'ukp	Korea, Republic of	08308
61	Pusan National University Hospital	Busan		Korea, Republic of	49241
62	Ajou University Hospital	Gyeonggi-do		Korea, Republic of	16499
63	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13620
64	Seoul National University Hospital	Seoul		Korea, Republic of	03080
65	Severance Hospital Yonsei University Health System	Seoul		Korea, Republic of	03722
66	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
67	Asan Medical Center - Oncology	Seoul		Korea, Republic of	5505
68	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan	83301
69	China Medical University Hospital - Oncology - Taichung	Taichung		Taiwan	40447
70	Taichung Veterans General Hospital	Taichung		Taiwan
71	Chi Mei Medical Center - YongKang	Tainan		Taiwan
72	National Taiwan University Hospital (NTUH)	Taipei		Taiwan	100225
73	Taipei Veterans General Hospital	Taipei		Taiwan	11217
74	Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital	Taipei		Taiwan
75	Mackay Memorial Hospital	Taipei		Taiwan
76	Vajira Hospital [SSU]	Dusit	Bangkok	Thailand	10300
77	Maharaj Nakorn Chiang Mai Hospital [SSU]	Chiang Mai	Muang	Thailand	50200
78	Sunpasitthiprasong Hospital	Ubon Ratchathani	Muang	Thailand	34000
79	King Chulalongkorn Memorial Hospital (Chulalongkorn University)	Bangkok	Panthumwan	Thailand	10330
80	Siriraj Hospital	Bangkok		Thailand	10700
81	Songklanagarind Hospital (Prince of Songkhla University)	Hat Yai		Thailand	90110
82	Srinagarind Hospital (Khon Kaen University)	Mueang Nonthaburi		Thailand	40002

Sponsors and Collaborators

• BeiGene

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT05564338
• Other Study ID Numbers: BGB-A317-Sitravatinib-303
• First Posted: Oct 3, 2022
• Last Update Posted: Feb 2, 2023
• Last Verified: Feb 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by BeiGene: hepatocellular carcinoma; sitravatinib; tislelizumab
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular

Study Results

No Results Posted as of Feb 2, 2023