A Study to Investigate Sitravatinib as Monotherapy and in Combination With Tislelizumab in Participants With Unresectable Locally Advanced or Metastatic Hepatocellular Carcinoma or Gastric/Gastroesophageal Junction Cancer
- Conditions
- Carcinoma, HepatocellularGastric/Gastroesophageal Junction Cancer
- Interventions
- Registration Number
- NCT03941873
- Lead Sponsor
- BeiGene
- Brief Summary
The purpose of this study was 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 (HCC) or gastric/gastroesophageal junction (G/GEJ) cancer.
- Detailed Description
This was 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 received study treatment (s) until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 111
- Histologically or cytologically confirmed, unresectable, locally advanced, or metastatic HCC/gastric cancer/GEJ cancer
- 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 informed consent form (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
- Active leptomeningeal disease or uncontrolled brain metastasis
- Active autoimmune diseases or history of autoimmune diseases that may relapse
- Any active malignancy ≤ 2 years before first dose of study drug(s)
- History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases including pulmonary fibrosis or acute lung diseases
- Severe chronic or active infections (including tuberculosis infection) 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 adverse events 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sitravatinib 120 mg + Tislelizumab Sitravatinib Sitravatinib 120 mg orally once daily in 21-day cycles with tislelizumab 200 mg IV once every 3 weeks in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer Sitravatinib 120 mg + Tislelizumab Tislelizumab Sitravatinib 120 mg orally once daily in 21-day cycles with tislelizumab 200 mg IV once every 3 weeks in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer Sitravatinib Monotherapy: 80 mg Sitravatinib Sitravatinib 80 mg orally once daily in 21-day cycles in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer Sitravatinib Monotherapy: 120 mg Sitravatinib Sitravatinib 120 mg orally once daily in 21-day cycles in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer Sitravatinib 80 mg + Tislelizumab Sitravatinib Sitravatinib 80 mg orally once daily in 21-day cycles with tislelizumab 200 mg intravenously (IV) once every 3 weeks in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer Sitravatinib 80 mg + Tislelizumab Tislelizumab Sitravatinib 80 mg orally once daily in 21-day cycles with tislelizumab 200 mg intravenously (IV) once every 3 weeks in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events Up to approximately 4 years and 1 month Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0), including relevant physical examination, electrocardiograms, and laboratory assessments. Safety analysis set is presented by dose, as prespecified in the statistical analysis plan (SAP).
Objective Response Rate (ORR) Up to approximately 4 years and 1 month ORR is defined as the percentage of participants whose best overall response (BOR) is the confirmed complete response (CR) or partial response (PR) assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan.
- Secondary Outcome Measures
Name Time Method Maximum Plasma Concentration (Cmax) for Sitravatinib Predose and up to 24 hours postdose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21) (21 days in each cycle) Time to Maximum Plasma Concentration (Tmax) for Sitravatinib Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) Clearance After Oral Administration (CL/F) for Sitravatinib Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) Observed Accumulation Ratio (Ro) for AUC(0-tau) for Sitravatinib Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) Plasma Concentrations of Sitravatinib Predose and 6 hours postdose in Cycle 5 Day 1 (21 days in each cycle) Duration of Response (DOR) Up to approximately 4 years and 1 month DOR is defined as the time from the first determination of an objective response until the first documentation of progressive disease as assessed by investigator per RECIST v1.1, or death, whichever comes first. Results are reported for indication groups with responders, defined as complete response (CR) or partial response (PR). Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan.
Disease Control Rate (DCR) Up to approximately 4 years and 1 month DCR is defined as the percentage of participants with BOR as CR, PR, or stable disease (SD) assessed by investigator per RECIST v1.1. Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan.
Progression-free Survival (PFS) Up to approximately 4 years and 1 month PFS is defined as the time from the date of first dose to the date of first documentation of progressive disease assessed by the investigator per RECIST v1.1 or death, whichever occurs first. Safety analysis set is presented by indication group, as prespecified in the statistical analysis plan.
Trial Locations
- Locations (18)
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
🇨🇳Guangzhou, Guangdong, China
Nanfang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Zhongnan Hospital of Wuhan University Wuhan
🇨🇳Wuhan, Hubei, China
General Hospital of Eastern Theatre Command Qihuaiyuan Branch(the St Hospital of Chinese Pla)
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
Liaoning Cancer Hospital and Institute
🇨🇳Shenyang, Liaoning, China
Affiliated Zhongshan Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Shanghai East Hospital Branch Hospital
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China