A Phase 1b Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Sitravatinib in Combination With Tislelizumab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 216
- 试验地点
- 19
- 主要终点
- Number of Participants With Adverse Events (AEs)
研究概览
简要总结
This was an open-label, multicenter, non-randomized Phase 1b clinical trial for participants with histologically or cytologically confirmed locally advanced or metastatic tumors including non-squamous or squamous non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), ovarian cancer (OC), or melanoma.
详细描述
All participants received sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks until occurrence of progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor. Participants were enrolled according to their tumor type and prior anti-programmed cell death protein-1 (PD-1)/PD-L1 antibody treatment into the following cohorts:
- Cohort A: Anti-PD-1/PD-L1 antibody refractory/resistant metastatic, non-squamous NSCLC
- Cohort B: Anti-PD-1/PD-L1 antibody naïve metastatic, non-squamous NSCLC
- Cohort C: Anti-PD-1/PD-L1 antibody refractory/resistant metastatic or advanced RCC
- Cohort D: Metastatic or advanced RCC without prior systemic therapy
- Cohort E: Anti-PD-1/PD-L1 antibody naïve recurrent and platinum resistant epithelial OC
- Cohort F: Anti-PD-1/PD-L1 antibody treated metastatic, squamous NSCLC
- Cohort G: Anti-PD-1/PD-L1 antibody refractory/resistant unresectable or metastatic melanoma
- Cohort H: PD-L1 positive, locally advanced or metastatic, non-squamous NSCLC without prior systemic treatment in the metastatic setting
- Cohort I: PD-L1 positive, locally advanced or metastatic, squamous NSCLC without prior systemic treatment in the metastatic setting
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •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)
- •At least 1 measurable lesion as defined by RECIST v1.1
- •Provide archival tumor tissue (formalin-fixed paraffin-embedded block [FFPE] with tumor tissue or unstained slides), if available.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- •Adequate hematologic and end-organ function
- •Participants with inactive/asymptomatic carrier, chronic, or active hepatitis B virus (HBV) must have HBV deoxyribonucleic acid (DNA) < 500 IU/mL (or 2500 copies/mL) at Screening
- •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 drugs and have a negative serum pregnancy test ≤ 7 days of first dose of study drugs
- •Non-sterile 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 drugs
排除标准
- •Unacceptable toxicity on prior anti-PD-1/PD-L1 treatment
- •Active leptomeningeal disease or uncontrolled brain metastasis
- •Active autoimmune diseases or history of autoimmune diseases that may relapse
- •Any active malignancy ≤ 2 years
- •Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before first dose of study drugs
- •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 drugs
- •Known history of human immunodeficiency virus (HIV) infection
- •Participants with active hepatitis C infection
- •Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drugs
- •Prior allogeneic stem cell transplantation or organ transplantation
- •Hypersensitivity to tislelizumab or sitravatinib, to any ingredient in the formulation, or to any component of the container
- •Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring within 6 months before first dose of study drugs
- •Concurrent participation in another therapeutic clinical trial
研究组 & 干预措施
Sitravatinib + Tislelizumab
Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks
干预措施: Sitravatinib (Drug)
Sitravatinib + Tislelizumab
Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs)
时间窗: Up to approximately 4 years and 2 months
Number of participants with treatment-emergent AEs (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs; TEAE was defined as an adverse event that had an onset date or a worsening in severity from baseline (pretreatment) on or after the first dose of study drug(s) up to 30 days following last dose of study drug(s) or initiation of a new anticancer therapy, whichever occurs first.
次要结局
- Clearance After Oral Administration (CL/F) for Sitravatinib(Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle)
- Duration of Response (DOR)(Up to approximately 4 years and 2 months)
- 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 post dose on C1D1 and C1D21; 21 days per cycle)
- Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib(Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle)
- Objective Response Rate (ORR)(Up to approximately 4 years and 2 months)
- Disease Control Rate (DCR)(Up to approximately 4 years and 2 months)
- Progression-free Survival (PFS)(Up to approximately 4 years and 2 months)
- Time to Maximum Plasma Concentration (Tmax) for Sitravatinib(Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle)
- Maximum Plasma Concentration (Cmax) for Sitravatinib(Predose and up to 24 hours post dose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21); 21 days per cycle)
- Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib(Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle)
- Observed Accumulation Ratio (Ro) for AUC0-tau for Sitravatinib(Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle)