A Phase II, Open-Label, Multicenter Study of Capmatinib in Subjects With MET Exon 14 Skipping Mutation Positive, Advanced, Non Small-Cell Lung Cancer That Has Metastasized to the Brain
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Overall Intracranial Response Rate (OIRR) in Cohort 1 by Blinded Independent Review Committee (BIRC) review
研究概览
简要总结
The purpose of this study is to establish the intracranial efficacy of single agent capmatinib in the population of treatment-naïve or pretreated with one or two prior lines of systemic therapies for advanced stage Non Small-Cell Lung Cancer (NSCLC) with MET exon 14 mutation that has metastasized to the brain.
Cohort 1 (asymptomatic brain metastases (BM) without prior brain therapy) has been selected to identify patients who are most likely to benefit from capmatinib therapy in this setting and to establish a clinically relevant response outcome.
Cohort 2 is a heterogeneous group of patients (symptomatic with and without prior brain therapy, asymptomatic with prior brain therapy, or with leptomeningeal disease.), and the outcomes will be descriptive only
详细描述
This is a prospectively designed, multicenter, open-label, two-cohort, phase II study to evaluate the intracranial efficacy of single agent capmatinib in participants with MET exon 14 mutated NSCLC and BM. Participants can be treatment naïve or pretreated with one or two prior lines of systemic therapies for advanced stage (stage IIIb - IV) NSCLC.
Approximately 60 participants will be enrolled globally and allocated to one of two cohorts:
Cohort 1 will enroll approximately 40 participants who are asymptomatic and without prior brain therapy.
Cohort 2 will enroll approximately 20 participants who are symptomatic with or without prior brain therapy or asymptomatic with prior brain therapy or with leptomeningeal disease.
All participants will be pre-screened for MET mutation and presence of BM will be documented at baseline by a radiologist/neuroradiologist.
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
- •Histologically confirmed stage IV (according to Version 8 of the American Joint Committee on Cancer (AJCC)) NSCLC that is EGFR wt, ALK rearrangement negative as assessed by a validated test as part of the participant's standard of care and has MET∆ex14 mutation per Novartis-designated central laboratory or (US only) locally with FoundationOne Companion Diagnostic (F1CDx) .
- •Treatment naïve or up to two prior lines of systemic therapy for stage IIIb-IV NSCLC
- •Measurable intracranial lesions:
- •Cohort 1 and Cohort 2 (without leptomeningeal carcinoma): At least 1 measurable intracranial lesion per RANO-BM criteria, documented by a radiologist/neuroradiologist (treated or untreated).
- •Cohort 2 (with leptomeningeal carcinoma): participants with leptomeningeal carcinoma may not have measurable lesions. In this circumstance, the participant's disease will be considered to have non-target lesions only at baseline and their response based on descriptive clinical criteria by physician assessment.
- •Capable of undergoing magnetic resonance imaging (MRI)
- •ECOG performance status of 0 or 1
排除标准
- •Only for Cohort 1: any neurological symptoms related to brain metastases
- •For participants in Cohort 2 with prior brain therapy: Treatment with stereotactic radiosurgery within 14 days prior to the start of study treatment or treatment with WBRT within 14 days prior to the start of study treatment
- •Prior treatment with any MET targeting therapy or HGF inhibitor
- •Participants with other known druggable molecular alterations (such as ROS1 translocation or BRAF mutation) who might be candidates to alternative targeted therapies as applicable per local regulations and treatment guidelines
- •Presence or history of ILD or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention)
- •Clinically significant, uncontrolled heart diseases including History of familial long QT syndrome, sudden death or congenital long QT syndrome
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Cohort 1
Participants who are asymptomatic and without prior brain therapy
干预措施: Capmatinib (Drug)
Cohort 2
Participants who are symptomatic with or without prior brain therapy or asymptomatic with prior brain therapy or with leptomeningeal disease
干预措施: Capmatinib (Drug)
结局指标
主要结局
Overall Intracranial Response Rate (OIRR) in Cohort 1 by Blinded Independent Review Committee (BIRC) review
时间窗: Up to 36 months
Overall Intracranial Response Rate (OIRR) in Cohort 1, defined as the proportion of participants with a confirmed best intracranial overall response of Complete Response (CR) or Partial Response (PR) per RANO-BM criteria as assessed by BIRC review
次要结局
- Time to response (TTR) by investigator and BIRC review(Up to 36 months)
- Duration of response (DOR) by investigator and BIRC review(Up to 36 months)
- Number of participants with dose interruptions(Up to 29 months)
- Time to deterioration in Functional Assessment of Cancer Therapy (FACT)-Brain Symptom Index (FBrSI) scores in Cohort 1(Day 1 and 15 of Cycle 1, Day 1 of cycles 2 to 11 and then every other cycle until end of treatment (up to 29 months). Cycle=28 days)
- Change from baseline in score as per European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) questionnaire(Day 1 of cycle 1 to 11 and then every other cycle until end of treatment (up to 29 months). Cycle=28 days)
- Number of participants with dose reductions(Up to 29 months)
- Dose intensity(Up to 29 months)
- Change from baseline in score as per FACT-Brain Symptom Index (FBrSI) in Cohort 2(Day 1 and 15 of Cycle 1, Day 1 of cycles 2 to 11 and then every other cycle until end of treatment (up to 29 months). Cycle=28 days)
- Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30(Day 1 of cycle 1 to 11 and then every other cycle until end of treatment (up to 29 months). Cycle=28 days)
- Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13)(Day 1 of cycle 1 to 11 and then every other cycle until end of treatment (up to 29 months). Cycle=28 days)
- Overall Intracranial Response Rate (OIRR) in Cohort 1 by investigator review(Up to 36 months)
- Time to intracranial tumor Response (TTIR) by investigator and BIRC review(Up to 36 months)
- Extracranial Disease Control Rate (EDCR) by investigator and BIRC review(Up to 36 months)
- Duration of Extracranial Response (DOER) by investigator and BIRC review(Up to 36 months)
- Overall Extracranial Response Rate (OERR) by investigator and BIRC review(Up to 36 months)
- Time to Extracranial Response (TTER) by investigator and BIRC review(Up to 36 months)
- Overall Response Rate (ORR) per RECIST 1.1 by investigator and BIRC review(Up to 36 months)
- Progression free survival (PFS) by investigator and BIRC review(Up to 36 months)
- Overall survival (OS)(Up to 36 months)
- Percentage of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 36 months)
- Intracranial Disease Control Rate (IDCR) by investigator and BIRC review(Up to 36 months)
- Duration of Intracranial Response (DOIR) by investigator and BIRC review(Up to 36 months)
- Overall Intracranial Response Rate (OIRR) in Cohort 2 by investigator and BIRC review(Up to 36 months)