A Phase II Study Exploring the Safety, Tolerability and Preliminary Anti-tumor Activity of Sitravatinib With or Without Tislelizumab in Patients With Unresectable or Metastatic Melanoma
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR) in Arm A
研究概览
简要总结
In 2014, an estimated 7,000 patients were diagnosed of melanoma in China. It is growing at an annual rate of 3%-5% and approximately 20,000 new cases are reported each year recently.To date, CFDA only approved dacarbazine as first line chemotherapy and anti-PD-1 antibody monotherapy as second line. There is no standard of care after chemotherapy and anti-PD-1.
详细描述
This is an open-label, randomized, single center phase 2 study evaluating the efficacy and safety of sitravatinib in combination with tislelizumab for Chinese patients with unresectable or metastatic melanoma after disease progression from prior anti-PD-1 antibody and chemotherapy. The first 20 patients will be randomized in a 1:1 ratio to receive either sitravatinib plus tislelizumab (Arm A) or sitravatinb monotherapy (Arm B). After the completion of initial 20 patients, additional patients will be recruited until 24 efficacy evaluable patients achieved in Arm A
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •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)
- •Disease progression from prior chemotherapy and anti-PD-(L)1 therapy (including sequential or combined therapy, regardless of the order)
- •No antiPD-1/PD-L1 related toxicity during the prior treatment
- •Have not received other immunotherapy, including but not limited to anti-OX40, anti-TIGIT and anti-CD137, etc.
- •BRAF wild-type patients, or patients with BRAF mutations who are not suitable or refused to receive targeted therapy with BRAF inhibitors and/or MEK inhibitors
- •Have not been exposed to small molecule targeted drugs with anti-angiogenesis effect, or VEGFR TKI drugs
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- •Adequate hematologic and end-organ function
- •Have not received radiotherapy, endocrine therapy, molecular targeted therapy, or surgery within 2 weeks before the start of the study, and have recovered from the acute toxicity of the previous treatment
- •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
排除标准
- •Ocular melanoma
- •known NRAS mutations
- •Active leptomeningeal disease or brain metastases that are not well controlled.
- •History of active autoimmune disease
- •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 HIV 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 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
Arm A: tislelizumab+sitravatinib
Patients will receive sitravatinib 100 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: sitravatinib (Drug)
Arm A: tislelizumab+sitravatinib
Patients will receive sitravatinib 100 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: tislelizumab (Drug)
Arm B: sitravatinib
Patients will receive sitravatinib 100 mg orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: sitravatinib (Drug)
结局指标
主要结局
Overall response rate (ORR) in Arm A
时间窗: 12 months
defined as the proportion of participants with partial response or complete response as determined by the investigators based on RECIST v1.1
次要结局
- Overall response rate (ORR) in Arm B(12 months)
- Disease control rate (DCR) in Arm A and B(12 months)
- Progression-free survival (PFS) in Arm A and B(12 months)
- Incidence of Treatment-Emergent Adverse Events(12 months)
研究者
Jun Guo
Vice President
Peking University Cancer Hospital & Institute