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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
111
Administered orally as a capsule
Administered intravenously
The Second Hospital of Anhui Medical University
Hefei, Anhui, China
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, China
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
Guangzhou, Guangdong, China
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 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
Hubei Cancer Hospital
Wuhan, Hubei, China
General Hospital of Eastern Theatre Command Qihuaiyuan Branch(the St Hospital of Chinese Pla)
Nanjing, Jiangsu, China
...and 8 more locations
Number of Participants With Adverse Events
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).
Time frame: Up to approximately 4 years and 1 month
Objective Response Rate (ORR)
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.
Time frame: Up to approximately 4 years and 1 month
Duration of Response (DOR)
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.
Time frame: Up to approximately 4 years and 1 month
Disease Control Rate (DCR)
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.
Time frame: Up to approximately 4 years and 1 month
Progression-free Survival (PFS)
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.
Time frame: Up to approximately 4 years and 1 month
Maximum Plasma Concentration (Cmax) for Sitravatinib
Time frame: 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
Time frame: 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
Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Clearance After Oral Administration (CL/F) for Sitravatinib
Time frame: 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
Time frame: 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
Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib
Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Plasma Concentrations of Sitravatinib
Time frame: Predose and 6 hours postdose in Cycle 5 Day 1 (21 days in each cycle)
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