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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 111
- 试验地点
- 18
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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
干预措施: Tislelizumab (Drug)
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
干预措施: Sitravatinib (Drug)
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
干预措施: Sitravatinib (Drug)
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
干预措施: Sitravatinib (Drug)
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
干预措施: Sitravatinib (Drug)
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
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: 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)
时间窗: 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.
次要结局
- 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))