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 Hepatocellular Carcinoma or Gastric/Gastroesophageal Junction Cancer
Overview
- Phase
- Phase 1
- Intervention
- Tislelizumab
- Conditions
- Carcinoma, Hepatocellular
- Sponsor
- BeiGene
- Enrollment
- 111
- Locations
- 18
- Primary Endpoint
- Number of Participants With Adverse Events
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
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 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)
Arms & Interventions
Sitravatinib 80 mg + 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
Intervention: Tislelizumab
Sitravatinib 120 mg + 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
Intervention: Sitravatinib
Sitravatinib Monotherapy: 80 mg
Sitravatinib 80 mg orally once daily in 21-day cycles in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer
Intervention: Sitravatinib
Sitravatinib Monotherapy: 120 mg
Sitravatinib 120 mg orally once daily in 21-day cycles in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer
Intervention: Sitravatinib
Sitravatinib 80 mg + 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
Intervention: Sitravatinib
Sitravatinib 120 mg + 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
Intervention: Tislelizumab
Outcomes
Primary Outcomes
Number of Participants With Adverse Events
Time Frame: 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)
Time Frame: 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 Outcomes
- Duration of Response (DOR)(Up to approximately 4 years and 1 month)
- Disease Control Rate (DCR)(Up to approximately 4 years and 1 month)
- Progression-free Survival (PFS)(Up to approximately 4 years and 1 month)
- 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))