Phase II Pilot Study Evaluating Strategies to Overcome Resistance at the Time of Progression for Patients With Non-small Cell Lung Cancers Harboring Major Oncogenic Drivers
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Objective Response Rate in Patients With High PD-L1 Expressing Cancers After Failure of Targeted Therapy Defined as Complete or Partial Response According to the Investigator's Assessment
研究概览
简要总结
This phase II trial studies how well targeted therapy works in treating patients with incurable non-small cell lung cancer with a genetic mutation. Giving drugs that target other genetic mutations or other specific proteins may work better when a patient has cancer caused by a driver mutation and the treatment that targets that mutation stops working.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the objective response rate among patients with high PD-L1 expressing cancers after failure of targeted therapy.
SECONDARY OBJECTIVES:
I. To compare the overall survival for patients receiving treatment targeting primary mutations, secondary mutations, or immunotherapy at the time of progression on tyrosine kinase inhibitor therapy.
II. To assess the incidence of secondary mutations in this population according to smoking status.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically or cytologically confirmed incurable non-small cell lung cancer that harbors an activating mutation in EGFR, MET, BRAF, V600E, RET, HER2, translocation in Alk, or translocation in ROS-1
- •Patients must be receiving treatment or planning to start treatment with a tyrosine kinase inhibitor targeting the activated gene
- •Patients may not be receiving the treatment targeting the activated gene as part of a clinical treatment trial other than the Precision Oncology Trial
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
- •Total bilirubin =< 1.5 X institutional upper limit of normal
- •Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document
排除标准
- •Emergent need for palliative radiation
- •Patients may not be receiving any other investigational agents for the treatment of non-small cell lung cancer
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded; breastfeeding should be discontinued
研究组 & 干预措施
Arm I (nivolumab, pembrolizumab)
Patients receive nivolumab IV over 60 minutes every 2 weeks or pembrolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (nivolumab, pembrolizumab)
Patients receive nivolumab IV over 60 minutes every 2 weeks or pembrolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Nivolumab (Biological)
Arm I (nivolumab, pembrolizumab)
Patients receive nivolumab IV over 60 minutes every 2 weeks or pembrolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Pembrolizumab (Biological)
Arm II (kinase inhibitor, chemotherapy, immunotherapy)
Patients receive tyrosine kinase inhibitor therapy PO targeting the initial oncogenic driver or other treatment for about 3 weeks.
干预措施: Chemotherapy (Drug)
Arm II (kinase inhibitor, chemotherapy, immunotherapy)
Patients receive tyrosine kinase inhibitor therapy PO targeting the initial oncogenic driver or other treatment for about 3 weeks.
干预措施: Immunotherapy (Biological)
Arm II (kinase inhibitor, chemotherapy, immunotherapy)
Patients receive tyrosine kinase inhibitor therapy PO targeting the initial oncogenic driver or other treatment for about 3 weeks.
干预措施: Laboratory Biomarker Analysis (Other)
Arm III (kinase inhibitor, targeted therapy, other treatment)
Patients receive tyrosine kinase inhibitor therapy PO targeting initial oncogenic driver, a drug targeting the secondary mutation, or other treatment for about 3 weeks.
干预措施: Targeted Molecular Therapy (Drug)
Arm II (kinase inhibitor, chemotherapy, immunotherapy)
Patients receive tyrosine kinase inhibitor therapy PO targeting the initial oncogenic driver or other treatment for about 3 weeks.
干预措施: Tyrosine Kinase Inhibitor (Drug)
Arm III (kinase inhibitor, targeted therapy, other treatment)
Patients receive tyrosine kinase inhibitor therapy PO targeting initial oncogenic driver, a drug targeting the secondary mutation, or other treatment for about 3 weeks.
干预措施: Chemotherapy (Drug)
Arm III (kinase inhibitor, targeted therapy, other treatment)
Patients receive tyrosine kinase inhibitor therapy PO targeting initial oncogenic driver, a drug targeting the secondary mutation, or other treatment for about 3 weeks.
干预措施: Immunotherapy (Biological)
Arm III (kinase inhibitor, targeted therapy, other treatment)
Patients receive tyrosine kinase inhibitor therapy PO targeting initial oncogenic driver, a drug targeting the secondary mutation, or other treatment for about 3 weeks.
干预措施: Laboratory Biomarker Analysis (Other)
Arm III (kinase inhibitor, targeted therapy, other treatment)
Patients receive tyrosine kinase inhibitor therapy PO targeting initial oncogenic driver, a drug targeting the secondary mutation, or other treatment for about 3 weeks.
干预措施: Tyrosine Kinase Inhibitor (Drug)
结局指标
主要结局
Objective Response Rate in Patients With High PD-L1 Expressing Cancers After Failure of Targeted Therapy Defined as Complete or Partial Response According to the Investigator's Assessment
时间窗: Up to 1 year after failure of targeted therapy
Objective Response is defined as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). This outcome applies only to Arm I. \* Complete Response (CR): Disappearance of all target lesions, \* Partial Response (PR): At least a 30% decrease in the sum of the target lesions Progressive Disease (PD): At least a 20% increase in the sum of the target lesions, Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease
次要结局
- Number of Mutations in Secondary Genes for Patients With PD-L1 Expression < 50%(Up to 1 year after failure of targeted therapy)
- Overall Survival(From date of progression on primary targeted treatment to death, assessed up to 3 years.)
- Rate of Tobacco Use and Mutation Burden Based on PD-L1 Expression at Time of Progression(Assessed at enrollment into study.)
- Number of Participants With Adverse Events Measured Using Common Terminology Criteria for Adverse Events Version 4.0(Adverse events were collected following each cycle of treatment (1-4) and up to 30 days after the last dose of study treatment. The average collection time from start of treatment was 7 weeks, with a range of 3 to 11 weeks.)
- Objective Response Rates for Patients Without High PD-L1 Expressing Cancers(Up to 3 years after failure of targeted therapy)