A Phase III, Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib Versus SoC Docetaxel Chemotherapy in Previously Treated Patients With EGFR wt, ALK Negative, Locally Advanced or Metastatic (Stage IIIB/IIIC or IV) NSCLC Harboring MET Exon 14 Skipping Mutation (METΔex14).
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS) Per Blinded Independent Review Committee (BIRC) Using RECIST v1.1
研究概览
简要总结
The purpose of the study was to learn whether the study drug (capmatinib) helps to control lung cancer better compared to a single agent chemotherapy (docetaxel) and whether it is safe when given to patients suffering from a particular type of lung cancer. This type of cancer is called non-small cell lung cancer (NSCLC) with certain specific genetic alterations (called mutations) of a gene called MET, within a specific part of the gene called exon 14.
详细描述
Twenty-two patients with advanced or metastatic lung cancer, with these specific mutations in the MET gene but without changes in their epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genes, were enrolled in this study. Participants were randomly assigned to get either capmatinib or docetaxel in a 2 to 1 ratio. The randomization was stratified by prior lines of systemic therapy received for advanced/metastatic disease (one line vs. two lines).
During treatment, visits were scheduled every 21 days.
For all participants, the respective treatment (either with capmatinib or docetaxel) could be continued beyond initial disease progression as per RECIST 1.1 (as assessed by the investigator and confirmed by BIRC) if, in the judgment of the investigator, there was evidence of clinical benefit, and the participant wished to continue on the study treatment. After treatment discontinuation, all participants were followed for safety evaluations during the safety follow-up period, and the participant's status was collected every 12 weeks as part of the survival follow-up.
Participants randomized to docetaxel treatment were eligible to cross over to receive capmatinib treatment after BIRC-confirmed, RECIST 1.1-defined progressive disease and after meeting the eligibility criteria prior to crossover. This was the extension treatment phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Stage IIIB/IIIC (not amenable to surgery, radiation or multi modality therapy) or IV NSCLC (according to Version 8 of the American Joint Committee on Cancer (AJCC) Staging Manual) at the time of study entry.
- •Histologically or cytologically confirmed diagnosis of NSCLC that was:
- •EGFR wt. Assessed as part of participant's standard of care by a validated test for EGFR mutations as per local guidelines. The EGFR wt status (for EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations.
- •AND ALK rearrangement negative. Assessed as part of participant's standard of care by a validated test.
- •AND had METΔex14 mutation as determined by Novartis-designated central laboratory or by locally performed, tissue-based test, validated according to local regulation, from a Clinical Laboratory Improvement Amendments (CLIA)-certified US laboratory or an accredited local laboratory outside of the US. The positive METΔex14 mutation result as determined per local test must have been documented in the participant's source documents and in the CRF prior to entering main screening.
- •Mandatory provision of a formalin-fixed, paraffin embedded tumor tissue sample (archival tumor block or slides, or a newly obtained tumor sample) with quality and quantity sufficient to allow assessment of METΔex14 mutation status (as defined in the study [laboratory manual]). This pertained to all participants, including those who had a METΔex14 mutation result from a local test. Tumor samples must have contained at least 10% tumor content.
- •Participants must have progressed on one or two prior lines of systemic therapy for advanced/metastatic disease (stage IIIB/IIIC [not candidates for surgery, radiation or multi modality therapy] or IV NSCLC) and must have been docetaxel naïve and candidates for single agent chemotherapy (docetaxel). Treatment failure was defined as documented disease progression or intolerance to treatment, however, participants must have progressed on or after the last therapy before study entry.
- •At least one measurable lesion as defined by RECIST 1.1
- •Adequate organ function
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or
- •Life expectancy of at least 3 months.
排除标准
- •Prior treatment with any MET inhibitor or HGF-targeting therapy.
- •Participants with symptomatic central nervous system (CNS) metastases who were neurologically unstable or had required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
- •Participants with known druggable molecular alterations (such as ROS1 and RET rearrangement, BRAF mutation, KRAS mutation, NTRK fusion, etc.) which might have been a candidate for alternative targeted therapies.
- •Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention).
- •Substance abuse, active infection or other severe, acute, or chronic medical or psychotic conditions or laboratory abnormalities that in the opinion of the investigator may have increased the risk associated with study participation.
研究组 & 干预措施
Capmatinib
400 mg, capmatinib tablets, administered orally twice daily
干预措施: Capmatinib (Drug)
Docetaxel
Docetaxel 75 mg/m^2 solution administered by intravenous infusion on Day 1 of every 21-day cycle
干预措施: Docetaxel (Drug)
结局指标
主要结局
Progression-free Survival (PFS) Per Blinded Independent Review Committee (BIRC) Using RECIST v1.1
时间窗: From randomization to the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 21 months
Progression-free survival was defined as the time from the date of randomization to the date of the first documented progressive disease (PD) as assessed by BIRC according to RECIST 1.1, or death due to any cause. PD=At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm\^2. PFS was censored at the date of the last adequate tumor assessment, if no PFS event was observed prior to the analysis cut-off date.
次要结局
- Change From Baseline in Score as Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30(Baseline, Cycle (C) 3, Day (D) 1 and then every 6 weeks up to approximately 21 months, end of treatment. Each cycle duration was 21 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)(Baseline, Cycle (C) 3, Day (D) 1 and then every 6 weeks up to approximately 21 months, end of treatment. Each cycle duration was 21 days.)
- Change From Baseline in Score as Per European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Questionnaire(Baseline, Cycle (C) 3, Day (D) 1 and then every 6 weeks up to approximately 21 months, end of treatment. Each cycle duration was 21 days.)
- Time to Symptom Deterioration for Chest Pain, Cough and Dyspnea Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13)(Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12, 18 weeks post treatment. Each cycle duration was 21 days.)
- Time to Deterioration for Global Health Status /QoL Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30(Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12, 18 weeks post treatment. Each cycle duration was 21 days.)
- Overall Response (ORR) Per RECIST 1.1 by BIRC(Up to approximately 21 months)
- Time to Response (TTR) Per RECIST 1.1 by BIRC(From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months)
- Overall Response Rate (ORR) Per RECIST 1.1 by Investigator(Up to approximately 21 months)
- Time to Response (TTR) Per RECIST 1.1 by Investigator(From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months)
- Duration of Response (DOR) Per RECIST 1.1 by BIRC(From first documented response to first documented progression or death due to any cause, whichever came first, assessed up to approximately 21 months)
- Duration of Response (DOR) Per RECIST 1.1 by Investigator(From first documented response to first documented progression or death due to any cause, whichever came first, assessed up to approximately 21 months)
- Disease Control Rate (DCR) Per RECIST 1.1 by BIRC(Up to approximately 21 months)
- Disease Control Rate (DCR) Per RECIST 1.1 by Investigator(Up to approximately 21 months)
- Progression-free Survival (PFS) Per Investigator Using RECIST v1.1(From randomization to the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 21 months)
- Overall Survival (OS)(From randomization to death due to any cause, assessed up to approximately 36 months)
- Overall Intracranial Response Rate (OIRR)(Up to approximately 21 months)
- Duration of Intracranial Response (DOIR)(From date of first documented intracranial response (CR or PR) to first documented intracranial progression, assessed up to approximately 21 months)
- Time to Intracranial Response (TTIR)(From date of randomization to first documented intracranial response of either CR or PR, assessed up to approximately 21 months)
- Intracranial Disease Control Rate (IDCR)(Up to approximately 21 months)
- Plasma Capmatinib Concentration(Cycle (C) 1 Day (D) 15 pre-dose, 1 and 4 hours post-dose, C3 D1 pre-dose. Each cycle duration was 21 days.)