A Phase II, Open-Label, Multicenter, Multicohort Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Patients With Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 19
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This is a study to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab in participants with advanced solid tumors including the following cohorts: squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma (UC), and renal cell carcinoma (RCC).
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
- •General Inclusion Criteria:
- •Age ≥18 years
- •Ability to comply with the study protocol, in the investigator's judgment
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Life expectancy ≥3 months, as determined by the investigator
- •Adequate hematologic and end-organ function
- •Cancer-Related Inclusion Criteria:
- •Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST v1.
- •Availability to provide a representative tumor specimen biopsy
- •Evidence of tumor progression on or after the last treatment regimen received and within 6 months prior to study enrollment
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a non-hormonal contraceptive method with a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab and within 3 months after the last dose of cobimetinib
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for at least 3 months after the last dose of cobimetinib
排除标准
- •General Exclusion Criteria:
- •Inability to swallow medications
- •Malabsorption condition that would alter the absorption of orally administered medications
- •Poor peripheral venous access
- •Prior treatment with cobimetinib or a MEK inhibitor
- •Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- •Treatment with investigational therapy within 14 days prior to initiation of study treatment
- •Any anti-cancer therapy, including chemotherapy or hormonal therapy, within 2 weeks prior to initiation of study treatment
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- •Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells or any component of the atezolizumab formulation, or any component of the cobimetinib formulation
- •History of serous retinopathy, retinal vein occlusion (RVO), or evidence of ongoing serous retinopathy or RVO at baseline
- •Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
- •Uncontrolled tumor-related pain
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
- •Uncontrolled hypercalcemia (ionized calcium >1.5 millimoles per liter [mmol/L], calcium >12 milligrams per deciliter [mg/dL], or corrected calcium greater than the upper limit of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
- •Active or untreated central nervous system (CNS) metastases
- •Pregnancy or breastfeeding, or intending to become pregnant during the study
- •Exclusion Criteria based on Organ Function or Medical History
- •Cardiovascular
- •Patients who meet the following cardiovascular exclusion criterion will be excluded from study entry:
- •Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal or <50%, whichever is lower
- •Infections Patients who meet any of the following infection exclusion criteria will be excluded from study entry:
- •Positive human immunodeficiency virus (HIV) test at screening
- •Active hepatitis B virus (HBV) infection (chronic or acute)
- •Active hepatitis C virus (HCV) infection
- •Active tuberculosis
- •Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- •Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
研究组 & 干预措施
Cohort 1 - SCCHN - Treatment Naive
In participants with recurrent or advanced / metastatic SSCHN who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Cobimetinib (Drug)
Cohort 1 - SCCHN - Treatment Naive
In participants with recurrent or advanced / metastatic SSCHN who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Atezolizumab (Drug)
Cohort 2 - UC - Treatment Naive
In participants with advanced / metastatic UC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Cobimetinib (Drug)
Cohort 2 - UC - Treatment Naive
In participants with advanced / metastatic UC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Atezolizumab (Drug)
Cohort 3 - RCC - Treatment Naive
In participants with metastatic RCC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 milligrams (mg) once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Cobimetinib (Drug)
Cohort 3 - RCC - Treatment Naive
In participants with metastatic RCC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 milligrams (mg) once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Atezolizumab (Drug)
Cohort 4 - SCCHN - Previous Treatment Exposure
In participants with SCCHN whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Cobimetinib (Drug)
Cohort 4 - SCCHN - Previous Treatment Exposure
In participants with SCCHN whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Atezolizumab (Drug)
Cohort 5 - UC - Previous Treatment Exposure
In participants with UC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Cobimetinib (Drug)
Cohort 5 - UC - Previous Treatment Exposure
In participants with UC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Atezolizumab (Drug)
Cohort 6 - RCC - Previous Treatment Exposure
In participants with RCC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Cobimetinib (Drug)
Cohort 6 - RCC - Previous Treatment Exposure
In participants with RCC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
干预措施: Atezolizumab (Drug)
Cohort 7 - Biopsy Cohort
In participants with solid non-melanoma, non- hematologic tumors who previously developed primary or secondary resistance to an anti-PD-1 or anti-PD-L1 agent, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle. The first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1. Thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles.
干预措施: Cobimetinib (Drug)
Cohort 7 - Biopsy Cohort
In participants with solid non-melanoma, non- hematologic tumors who previously developed primary or secondary resistance to an anti-PD-1 or anti-PD-L1 agent, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle. The first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1. Thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles.
干预措施: Atezolizumab Cohort 7 (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to approximately 31 months
Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive tumor assessments ≥4 weeks apart, as determined by the investigators using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). CR was defined as disappearance of all lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions.
次要结局
- Overall Survival (OS)(Up to approximately 31 months)
- Progression-Free Survival (PFS)(Up to approximately 31 months)
- Duration of Response (DOR)(Up to approximately 22 months)
- Disease Control Rate (DCR)(At 16 weeks)
- Number of Participants With Adverse Events(Up to approximately 31 months)
- Maximum Plasma Concentration (Cmax) of Cobimetinib(Day 15 of Cycle 3 (cycle is 28 days): 2-4 hours after cobimetinib dose)
- Minimum Plasma Concentration (Cmin) of Cobimetinib(Day 15 of Cycle 3 (cycle is 28 days): prior to cobimetinib dose)
- Maximum Serum Concentration (Cmax) of Atezolizumab(30 minutes following end of atezolizumab infusion on Day 15 of Cycle 3 (each cycle is 28 days))
- Minimum Serum Concentration (Cmin) of Atezolizumab(Prior to atezolizumab infusion on Day 1 of Cycles (each cycle is 28 days) 2, 4, 8, 12, and 16, Day 15 of Cycle 3)
- Number of Participants With Anti-drug Antibodies (ADAs)(Day 1 of Cycles (each cycle is 28 days) 1, 2, 4, 8, 12, and 16; Day 15 of Cycle 3; at atezolizumab treatment discontinuation visit, and <90 days after last atezolizumab infusion (up to approximately 31 months))