A Phase 1b/2 Study Of AVB-S6-500 In Combination With Cabozantinib, AVB-S6-500 In Combination With Cabozantinib and Nivolumab, and AVB-S6-500 Monotherapy in Patients With Advanced or Metastatic Clear Cell Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 72
- 试验地点
- 17
- 主要终点
- Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (ORR)
研究概览
简要总结
This is a Phase 1b/2 study of AVB-S6-500 designed to evaluate the safety and efficacy of AVB-S6-500 in combination with cabozantinib, AVB-S6-500 in combination with cabozantinib and nivolumab and AVB-S6-500 monotherapy in subjects with advanced or metastatic clear cell renal cell carcinoma (ccRCC). The phase 1b portion of the study is open label and patients with advanced ccRCC who had progressed on or after at least one prior line of treatment will receive AVB-S6-500 + cabozantinib. Two dose levels will be evaluated. The Phase 2 portion of the study is open-label 3-part study to evaluate efficacy and tolerability of AVB-S6-500 + cabozantinib, AVB-S6-500 + cabozantinib + nivolumab, and AVB-S6-500 alone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Age 18 years or older
- •Histologically confirmed advanced or metastatic clear cell Renal Cell Carcinoma confirmed by imaging. Phase 1b and Phase 2 Part A: has progressed on/after at least one front-line of treatment; Phase 2 Part B: No prior systemic treatment; Phase 2 Part C: not amenable to curative intent therapy.
- •Must have radiologic imaging with a computed tomography (CT) scan or magnetic resonance imaging (MRI) within 28 days of enrollment
- •Must have at least one measurable lesion according to RECIST 1.1
- •ECOG performance status of 0-1
- •Adequate bone marrow, liver and kidney function
- •Life expectancy of >12 weeks
- •At least 28 days between termination of prior major surgery or anticancer therapy or 14 days from last radiation therapy and administration of AVB-S6-500
排除标准
- •Received prior treatment with cabozantinib (Phase1b and Phase 2 Part A)
- •Received prior treatment with nivolumab (Phase 2 Part B)
- •Concurrent anti-cancer therapy or any other interventional treatment or other interventional research trial
- •History of prior malignancy within the past 3 years except adequately treated basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast
- •Symptomatic CNS metastasis or metastases
- •Active GI disease that would impact absorption of cabozantinib
- •Nephrotic range proteinuria at screening
- •Evidence of pleural effusion, ascites etc that requires therapeutic intervention within 28 days prior to AVB-S6-500 administration
- •Phase 2 Part A and Part B: Has had a major bleed in the last 3 months, uncontrolled hypertension despite treatment with antihypertensives or is not appropriate for treatment with cabozantinib in the Investigator's opinion
- •Serious active infection requiring IV antibiotics and/or hospitalization at study entry
- •Phase 2 Part B: Has active, known or suspected autoimmune disease, defined as requiring systemic treatment
- •Active COVID-19, HIV, Hepatitis B or Hepatitis C virus.
研究组 & 干预措施
Phase 1b: Batiraxcept + cabozantinib
Two dose levels of batiraxcept administered Q2W (once every two weeks) in combination with QD (once a day) cabozantinib will be evaluated.
干预措施: Cabozantinib (Cabo) (Drug)
Phase 1b: Batiraxcept + cabozantinib
Two dose levels of batiraxcept administered Q2W (once every two weeks) in combination with QD (once a day) cabozantinib will be evaluated.
干预措施: Batiraxcept (Drug)
Phase 2 Part A: batiraxcept + cabozantinib
One dose level of batiraxcept administered Q2W in combination with QD cabozantinib will be evaluated.
干预措施: Batiraxcept (Drug)
Phase 2 Part A: batiraxcept + cabozantinib
One dose level of batiraxcept administered Q2W in combination with QD cabozantinib will be evaluated.
干预措施: Cabozantinib (Cabo) (Drug)
Phase 2 Part B: batiraxcept + cabozantinib + nivolumab
One dose level of batiraxcept administered Q2W in combination with QD cabozantinib and nivolumab.
干预措施: Batiraxcept (Drug)
Phase 2 Part B: batiraxcept + cabozantinib + nivolumab
One dose level of batiraxcept administered Q2W in combination with QD cabozantinib and nivolumab.
干预措施: Cabozantinib (Cabo) (Drug)
Phase 2 Part B: batiraxcept + cabozantinib + nivolumab
One dose level of batiraxcept administered Q2W in combination with QD cabozantinib and nivolumab.
干预措施: Nivolumab (Drug)
Phase 2 Part C: batiraxcept alone
One dose level of batiraxcept administered Q2W will be evaluated.
干预措施: Batiraxcept (Drug)
结局指标
主要结局
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (ORR)
时间窗: 30 months
Measured by objective response rate (ORR) in patients receiving AVB-S6-500 + cabozantinib + nivolumab in Phase 2 Part B. ORR is proportion of subjects who have a partial or complete confirmed response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Identify the recommended Phase 2 dose of AVB-S6-500 in combination with cabozantinib
时间窗: 10 months
Measured by dose limiting toxicities experienced in Phase 1b
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (ORR)
时间窗: 30 months
Measured by objective response rate (ORR) in patients receiving AVB-S6-500 + cabozantinib in Phase 1b and Phase 2 Part A. ORR is proportion of subjects who have a partial or complete confirmed response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Anti-tumor activity of AVB-S6-500 alone (DOR)
时间窗: 30 months
Measured by duration of response (DOR) in patients receiving AVB-S6-500 in Phase 2 Part C. DOR is measured from the date of partial or complete response to therapy until the cancer progresses.
Anti-tumor activity of AVB-S6-500 alone (CBR)
时间窗: 30 months
Measured by clinical benefit rate (CBR) in patients receiving AVB-S6-500 in Phase 2 Part C. CBR is the proportion of subjects who have a complete or partial response to therapy or maintain stable disease.
Anti-tumor activity of AVB-S6-500 alone (PFS)
时间窗: 30 months
Measured by progression-free survival (PFS) in patients receiving AVB-S6-500 in Phase 2 Part C. PFS is the time from treatment until radiological disease progression or death.
Incidence of adverse events in Phase 1b as graded by NCI-CTCAE version 5.0
时间窗: 10 months
Safety and tolerability of AVB-S6-500 in combination with cabozantinib.
Anti-tumor activity of AVB-S6-500 alone (OS)
时间窗: 60 months
Measured by overall survival (OS) in patients receiving AVB-S6-500 in Phase 2 Part C. OS is the time from the start of the treatment until death.
Anti-tumor activity of AVB-S6-500 alone (ORR)
时间窗: 30 months
Measured by objective response rate (ORR) in patients receiving AVB-S6-500 in Phase 2 Part C. ORR is proportion of subjects who have a partial or complete confirmed response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
次要结局
- Pharmacokinetics: Cmax(30 months)
- Pharmacokinetics: Tmax(30 months)
- Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (OS)(60 months)
- Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (DOR)(30 months)
- Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (CBR)(30 months)
- Incidence of adverse events in Phase 2 Part C as graded by NCI-CTCAE version 5.0(30 months)
- Incidence of adverse events in Phase 2 Part B as graded by NCI-CTCAE version 5.0(30 months)
- Pharmacokinetics: AUC(30 months)
- Pharmacodynamic marker assessment(30 months)
- Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (CBR)(30 months)
- Pharmacokinetics: t1/2(30 months)
- Anti-drug antibody (ADA) titers(30 months)
- Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (DOR)(30 months)
- Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (PFS)(30 months)
- Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (PFS)(30 months)
- Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (OS)(60 months)