Back to resultsA Study to Investigate Sitravatinib as Monotherapy and in Combination With Tislelizumab in Participants With Unresectable Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) or Gastric/Gastroesophageal Junction Cancer (GC/GEJC)
Primary Purpose
Carcinoma, Hepatocellular, Gastric/Gastroesophageal Junction Cancer
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Sitravatinib
Sitravatinib plus Tislelizumab
Sitravatinib
Sitravatinib and tislelizumab
Sitravatinib and tislelizumab
Sitravatinib and tislelizumab
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring Carcinoma, HCC, G/GEJ Cancer
Eligibility Criteria
Key Inclusion Criteria:
- Histologically or cytologically confirmed, unresectable, locally advanced, or metastatic HCC/GC/GEJC
- Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
- Age ≥ 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place)
- Adequate organ function
- Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drug(s), and have a negative serum pregnancy test ≤ 7 days of first dose of study drug(s)
- Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drug(s)
- Failed current standard-of-care treatment, or standard-of-care treatment is considered not appropriate at present
Key Exclusion Criteria:
- Active leptomeningeal disease or uncontrolled brain metastasis.
- Active autoimmune diseases or history of autoimmune diseases that may relapse
- Any active malignancy ≤ 2 years
- History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc
- Severe chronic or active infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose of study drug(s).
- Known history of human immunodeficiency virus (HIV) infection
- Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers.
- Any major surgical procedure requiring general anesthesia ≤ 28 days before the first dose of study drug(s)
- Prior allogeneic stem cell transplantation or organ transplantation
- Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
- Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring
- Any systemic chemotherapy within 28 days of the first dose of study drug(s) or hormone therapy, targeted therapy, or any investigational therapies Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities)
- Inability to swallow capsules or disease significantly affecting gastrointestinal function
- Pregnant or breastfeeding woman
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- The Second Hospital of Anhui Medical University
- Beijing Cancer Hospital
- Fujian Medical university union hospital
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
- Nanfang Hospital
- Harbin Medical University Cancer Hospital
- Union Hospital Tongji Medical College Huazhong University of Science and Technology
- Hubei cancer hospital
- Zhongnan Hospital of Wuhan University
- The 81st Hospital of Chinese PLA
- The First affiliated hospital of Nanchang University
- Liaoning Cancer Hospital & Institute
- Zhongshan Hospital Fudan University
- Fudan University Shanghai Cancer Center
- Shanghai East Hospital
- Sir Run Run Shaw Hospital Zhejiang University School of Medicine
- The First Affiliated Hospital Zhejiang University
- Zhejiang Cancer Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Sitravatinib monotherapy
Sitravatinib plus Tislelizumab
Anti-PD-1/PD-L1 Antibody Naïve or R/R HCC (Monotherapy)
Anti-PD-1/PD-L1 antibody naive HCC(Combination)
Anti-PD-1/PD-L1 antibody refractory/resistant HCC
Anti-PD-1/PD-L1 antibody naive G/GEJ cancer
Arm Description
Two dose levels of sitravatinib as monotherapy, 80 mg once daily and 120 mg once daily, will be evaluated in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer. A modified 3+3 design will be used in the dose escalation to confirm recommended Phase 2 dose (RP2D)
The combination dose escalation of sitravatinib (80 mg once daily and 120 mg once daily; modified 3+3 design) with tislelizumab (200 mg every 3 weeks, in both cohorts) will be evaluated in unresectable locally advanced or metastatic HCC or G/GEJ cancer participants . If the combination dose of 80 mg sitravatinib and 200 mg tislelizumab has been declared tolerable, the dose of sitravatinib will be escalated to 120 mg and tislelizumab will remain fixed at 200 mg. Approximately 12 to 24 evaluable participants will be treated. The dose of tislelizumab during dose escalation for the combination will be kept fixed at 200 mg
Outcomes
Primary Outcome Measures
Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs) per NCI-CTCAE version 5.0
Phase 2: Objective response rate (ORR)
ORR based on RECIST v1.1 by investigator
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03941873
Brief Title
A Study to Investigate Sitravatinib as Monotherapy and in Combination With Tislelizumab in Participants With Unresectable Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) or Gastric/Gastroesophageal Junction Cancer (GC/GEJC)
Official Title
A Phase 1/2 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Sitravatinib as Monotherapy and in Combination With Tislelizumab in Patients With Unresectable Locally Advanced or Metastatic HCC or GC/GEJC
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
February 28, 2019 (Actual)
Primary Completion Date
March 31, 2023 (Actual)
Study Completion Date
March 31, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BeiGene
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety,tolerability, pharmacokinetics and preliminary antitumor activity of sitravatinib as monotherapy and in combination with tislelizumab in participants with unresectable locally advanced or metastatic hepatocellular carcinoma or gastric/gastroesophageal junction cancer.
Detailed Description
This is an open-label, multicenter Phase 1/2 clinical study for participants with histologically or cytologically confirmed unresectable locally advanced or metastatic HCC or G/GEJ cancer. All participants will receive study treatment (s) until progressive disease (PD), unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor. This study consists of the following phases.
Phase 1 (Dose escalation for sitravatinib as monotherapy and in combination with tislelizumab): Two dose levels of sitravatinib as monotherapy, 80 mg once daily and 120 mg once daily, will be evaluated in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer. A modified 3+3 design will be used in the dose escalation. Approximately 6 to 12 DLT evaluable participants will be treated with sitravatinib as monotherapy. The combination dose escalation of sitravatinib (80 mg once daily and 120 mg once daily; modified 3+3 design) with tislelizumab (200 mg every 3 weeks, in both cohorts) will be evaluated in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer. Approximately 12 to 24 DLT evaluable participants will be treated with sitravatinib in combination with tislelizumab.
Phase 2 (Dose expansion for sitravatinib as monotherapy and in combination with tislelizumab): Approximately 20 participants will be enrolled in each cohort. There will be a total of 4 cohorts in the study.
Cohort A: Anti-PD-1/PD-L1 Antibody Naïve or Refractory/Resistant HCC
Cohort B: Anti-PD-1/PD-L1 antibody naive HCC
Cohort C: Anti-PD-1/PD-L1 antibody refractory/resistant HCC
Cohort D: Anti-PD-1/PD-L1 antibody naive G/GEJ cancer
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular, Gastric/Gastroesophageal Junction Cancer
Keywords
Carcinoma, HCC, G/GEJ Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
111 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sitravatinib monotherapy
Arm Type
Experimental
Arm Description
Two dose levels of sitravatinib as monotherapy, 80 mg once daily and 120 mg once daily, will be evaluated in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer. A modified 3+3 design will be used in the dose escalation to confirm recommended Phase 2 dose (RP2D)
Arm Title
Sitravatinib plus Tislelizumab
Arm Type
Experimental
Arm Description
The combination dose escalation of sitravatinib (80 mg once daily and 120 mg once daily; modified 3+3 design) with tislelizumab (200 mg every 3 weeks, in both cohorts) will be evaluated in unresectable locally advanced or metastatic HCC or G/GEJ cancer participants . If the combination dose of 80 mg sitravatinib and 200 mg tislelizumab has been declared tolerable, the dose of sitravatinib will be escalated to 120 mg and tislelizumab will remain fixed at 200 mg. Approximately 12 to 24 evaluable participants will be treated. The dose of tislelizumab during dose escalation for the combination will be kept fixed at 200 mg
Arm Title
Anti-PD-1/PD-L1 Antibody Naïve or R/R HCC (Monotherapy)
Arm Type
Experimental
Arm Title
Anti-PD-1/PD-L1 antibody naive HCC(Combination)
Arm Type
Experimental
Arm Title
Anti-PD-1/PD-L1 antibody refractory/resistant HCC
Arm Type
Experimental
Arm Title
Anti-PD-1/PD-L1 antibody naive G/GEJ cancer
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Sitravatinib
Intervention Description
Study participants will receive sitravatinib capsule once daily
Intervention Type
Drug
Intervention Name(s)
Sitravatinib plus Tislelizumab
Intervention Description
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Sitravatinib
Intervention Description
Study participants will receive sitravatinib capsule once daily.
Intervention Type
Drug
Intervention Name(s)
Sitravatinib and tislelizumab
Intervention Description
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Sitravatinib and tislelizumab
Intervention Description
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Sitravatinib and tislelizumab
Intervention Description
Study participants will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.
Primary Outcome Measure Information:
Title
Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs) per NCI-CTCAE version 5.0
Time Frame
Up to approximately 3 years
Title
Phase 2: Objective response rate (ORR)
Description
ORR based on RECIST v1.1 by investigator
Time Frame
Up to approximately 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Histologically or cytologically confirmed, unresectable, locally advanced, or metastatic HCC/GC/GEJC
Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
Age ≥ 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place)
Adequate organ function
Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drug(s), and have a negative serum pregnancy test ≤ 7 days of first dose of study drug(s)
Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drug(s)
Failed current standard-of-care treatment, or standard-of-care treatment is considered not appropriate at present
Key Exclusion Criteria:
Active leptomeningeal disease or uncontrolled brain metastasis.
Active autoimmune diseases or history of autoimmune diseases that may relapse
Any active malignancy ≤ 2 years
History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc
Severe chronic or active infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose of study drug(s).
Known history of human immunodeficiency virus (HIV) infection
Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers.
Any major surgical procedure requiring general anesthesia ≤ 28 days before the first dose of study drug(s)
Prior allogeneic stem cell transplantation or organ transplantation
Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring
Any systemic chemotherapy within 28 days of the first dose of study drug(s) or hormone therapy, targeted therapy, or any investigational therapies Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities)
Inability to swallow capsules or disease significantly affecting gastrointestinal function
Pregnant or breastfeeding woman
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jin Li, PhD
Organizational Affiliation
Shanghai East Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Shukui Qin, MD
Organizational Affiliation
The 81st hospital of Chinese PLA
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Hospital of Anhui Medical University
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230000
Country
China
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Facility Name
Fujian Medical university union hospital
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350001
Country
China
Facility Name
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510120
Country
China
Facility Name
Nanfang Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Facility Name
Harbin Medical University Cancer Hospital
City
Harbin
State/Province
Heilongjiang
ZIP/Postal Code
150000
Country
China
Facility Name
Union Hospital Tongji Medical College Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430000
Country
China
Facility Name
Hubei cancer hospital
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430070
Country
China
Facility Name
Zhongnan Hospital of Wuhan University
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430071
Country
China
Facility Name
The 81st Hospital of Chinese PLA
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210000
Country
China
Facility Name
The First affiliated hospital of Nanchang University
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330006
Country
China
Facility Name
Liaoning Cancer Hospital & Institute
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
110042
Country
China
Facility Name
Zhongshan Hospital Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200120
Country
China
Facility Name
Shanghai East Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200120
Country
China
Facility Name
Sir Run Run Shaw Hospital Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Facility Name
The First Affiliated Hospital Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
A Study to Investigate Sitravatinib as Monotherapy and in Combination With Tislelizumab in Participants With Unresectable Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) or Gastric/Gastroesophageal Junction Cancer (GC/GEJC)
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