A Phase 1/2 Study to Investigate the Safety, Pharmacokinetics and Efficacy of CRB-601, a Monoclonal Antibody Against Integrin avb8, in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 156
- 试验地点
- 26
- 主要终点
- Occurance of Dose-limiting toxicities
研究概览
简要总结
The purpose of this study is to determine the safety, blood concentrations and treatment effect of CRB-601 in combination with immunotherapy in patients who have advanced solid tumors (cancer) and have exhausted other therapeutic options.CRB-601 targets a protein called avb8 integrin which is expressed by some cancers and not others. This study will focus on tumor types which are know to highly or moderately express this protein.
Researchers will evaluate the side effects caused by treatment, levels of CRB-601 in the blood, and the effect on the participant cancer. This will help researchers understand the right dose of CRB-601 to use for treatment and whether it is an effective treatment to combine with standard of care treatments such as immunotherapy. It will also help the researchers understand whether combining CRB-601 with standard-of-care immunotherapy and immune-priming radiotherapy is a safe and effective approach to treat cancer.
Participants in the study will receive CRB-601 via an infusion every two weeks either alone or in combination with immunotherapy.
There will be assessments to check on the participants general health status (including blood tests) and adverse effects. Participants will also receive regular CT or MRI scans to evaluate the effect of CRB-601 on their cancer. Participants will continue to visit the clinic every two weeks while they are receiving benefit from treatment. If their cancer progresses, participants will be asked to continue to be followed-up by the researchers to understand long-term outcomes, even if they receive other treatments.
详细描述
CRB-601-01 is a three-part interventional study which aims to:
- To determine the maximum tolerated dose (MTD) and pharmacologically active dose range (PADR) for CRB-601 administered as a monotherapy in patients with select relapsed/refractory solid tumors who have progressed after at least one line of therapy
- To determine the optimized dose for CRB-601 when administered within the PADR in combination with anti-programmed (cell) death ligand 1 (anti-PD-(L)1) therapy ( in patients with select relapsed/refractory solid tumors who have progressed after at least one line of therapy
- To determine the optimized dose for CRB-601 when administered within the PADR in combination with anti-PD(L)-1 therapy in patients with select relapsed/refractory solid tumors who have progressed after at least one line of therapy
The study will be run in 3 parts (A-C), run sequentially.
Part A Dose Escalation
Part A is designed to evaluate the safety, tolerability, and determine the MTD of CRB-601 administered as monotherapy in participants with select relapsed/refractory solid tumors that are known to express avb8 integrin. All participants will have had disease progression (PD) after at least one line of therapy or have no other standard therapy of proven clinical benefit currently available or be recommended based on the investigator's individual risk-benefit assessment for the participant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 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
- •Confirmed diagnosis of select locally advanced or metastatic solid tumors that have progressed after at least one line of therapy or have no other standard therapy with proven clinical benefit available.
- •Measurable disease on imaging as assessed by RECIST 1.1 Eastern Cooperative Oncology Group (ECOG) performance status (PS) greater or equal to
- •Life expectancy of more than 12 weeks.
- •Adequate hematologic and end-organ function.
排除标准
- •History of solid tumor malignancies other than the disease under study within 3 years of study enrollment
- •History of and/or current cardiovascular events or conditions
- •Chronic severe liver disease or liver cirrhosis
- •Systemic autoimmune disease
- •Active thrombophlebitis, thromboembolism or hypercoagulability states or uncontrolled bleeding or diabetes.
- •Interstitial lung disease within 6 months of study enrollment.
- •Active or persistent infection
- •Other conditions that in the opinion of the Investigator would compromise the outcomes of the study.
研究组 & 干预措施
Part A: Dose 1 CRB-601 monotherapy
Dose 1 of CRB-601 (3mg/Kg) administered intravenously every two weeks
干预措施: CRB-601 monoclonal antibody (Drug)
Part A: Dose 2 of CRB-601 monotherapy
Dose 2 of CRB-601 (10mg/Kg) administered intravenously every two weeks
干预措施: CRB-601 monoclonal antibody (Drug)
Part A: Dose 3 of CRB-601 monotherapy
Dose 3 of CRB-601 (30mg/Kg) administered intravenously every two weeks
干预措施: CRB-601 monoclonal antibody (Drug)
Part B/Cohort 1: Dose level (low) CRB-601 in combination with anti-PD(L)-1
Dose (defined in Part A) of CRB-601 administered intravenously in combination with anti-PD(L)-1 therapy dosed as per label.
干预措施: CRB-601 monoclonal antibody (Drug)
Part B/Cohort 1: Dose level (low) CRB-601 in combination with anti-PD(L)-1
Dose (defined in Part A) of CRB-601 administered intravenously in combination with anti-PD(L)-1 therapy dosed as per label.
干预措施: Anti-PD-1 monoclonal antibody (Drug)
Part B/Cohort 2: Dose level (high) CRB-601 in combination with anti-PD(L)-1
High dose CRB-601 (defined in Part A) of CRB-601 administered intravenously in combination with anti-PD(L)-1 therapy dosed per label.
干预措施: CRB-601 monoclonal antibody (Drug)
Part B/Cohort 2: Dose level (high) CRB-601 in combination with anti-PD(L)-1
High dose CRB-601 (defined in Part A) of CRB-601 administered intravenously in combination with anti-PD(L)-1 therapy dosed per label.
干预措施: Anti-PD-1 monoclonal antibody (Drug)
Part B/Expansion: Dose level (defined in Part B/ Safety Le) CRB-601 in combination with anti-PD(L)-1
Dose (defined in Part B/ Safety Lead-In) or CRB-601 administered intravenously in combination with anti-PD(L)-1 therapy dosed per label.
干预措施: CRB-601 monoclonal antibody (Drug)
Part B/Expansion: Dose level (defined in Part B/ Safety Le) CRB-601 in combination with anti-PD(L)-1
Dose (defined in Part B/ Safety Lead-In) or CRB-601 administered intravenously in combination with anti-PD(L)-1 therapy dosed per label.
干预措施: Anti-PD-1 monoclonal antibody (Drug)
Part C - Low dose CRB-601 in combination with anti-PD(L)-1
Participants will receive a low dose of CRB-601 (defined in Part A &B) in combination with standard of care dose of anti-PD(L)-1 therapy.
干预措施: CRB-601 monoclonal antibody (Drug)
Part C - Low dose CRB-601 in combination with anti-PD(L)-1
Participants will receive a low dose of CRB-601 (defined in Part A &B) in combination with standard of care dose of anti-PD(L)-1 therapy.
干预措施: Anti-PD-1 monoclonal antibody (Drug)
Part C - High dose CRB-601 in combination with anti-PD(L)-1
Participants will receive a high dose of CRB-601 (defined in Part A &B) in combination with standard of care dose of anti-PD(L)-1 therapy.
干预措施: CRB-601 monoclonal antibody (Drug)
Part C - High dose CRB-601 in combination with anti-PD(L)-1
Participants will receive a high dose of CRB-601 (defined in Part A &B) in combination with standard of care dose of anti-PD(L)-1 therapy.
干预措施: Anti-PD-1 monoclonal antibody (Drug)
结局指标
主要结局
Occurance of Dose-limiting toxicities
时间窗: 28 days
Characterize the safety of CRB-601 in combination anti-PD(L)1 therapy
时间窗: 6 months
Incidence of treatment emergent adverse events and clinically significant changes in laboratory parameters, ECG, vital signs and physical exam findings over treatment duration
To evaluate the efficacy of CRB-601 in terms of DCR when administered in combination with anti-PD(L)-1
时间窗: 6 months
Disease Control Rate (Complete Responses plus Partial Responses plus Stable Disease for at least 4 months as determined by the Investigator using RECIST 1.1.
次要结局
- To evaluate the preliminary antitumor activity of CRB-601 in combination with anti-PD(L)1 therapy(6 months)
- To characterize the PK profile of CRB-601(28 Days)