Trial Outcomes & Findings for Study of Capmatinib in Chinese Adult Patients With Advanced Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation (NCT NCT04677595)

Participants took part in 17 investigative sites in China.

Participants underwent molecular pre-screening to confirm eligibility based on protocol-defined criteria. Upon confirmation, all screening evaluations were required to be completed within 28 days prior to administration of the first treatment dose. Following successful screening, the treatment period commenced on Cycle 1 Day 1.

Study of Capmatinib in Chinese Adult Patients With Advanced Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation

Tumor response was assessed by a blinded independent review committee (BIRC) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. The primary efficacy endpoint ORR was estimated and the exact 95% confidence interval (CI) was provided by cohort.

DOR only applies to patients whose best overall response is complete response (CR) or partial response (PR) based on BIRC assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response of CR or PR to the date of first documented progression or death due to any cause. If a patient did not have an event, DOR was censored as defined in the statistical analysis plan. DOR was estimated using the Kaplan-Meier method.

Tumor response was assessed by the investigator based on RECIST v1.1. ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

DOR only applies to patients whose best overall response is complete response (CR) or partial response (PR) based on investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response of CR or PR to the date of first documented progression or death due to any cause. If a patient did not have an event, DOR was censored as defined in the statistical analysis plan. DOR was estimated using the Kaplan-Meier method.

TTR is defined as the time from the start date of study drug to the first documented response of either CR or PR, which must be subsequently confirmed. If a patient did not have an event, TTR was censored as defined in the statistical analysis plan. Tumor response was assessed by BIRC and by the investigator based on RECIST v1.1. TTR was estimated using the Kaplan-Meier method.

DCR is the percentage of patients with a best overall response of CR, PR or stable disease (SD), based on BIRC review and local investigator assessment per RECIST v1.1.

PFS is defined as the time from the start date of study drug to the date of the first radiologically documented progressive disease (PD) or death due to any cause. If a patient did not have an event, PFS was censored as defined in the statistical analysis plan. Tumor response was assessed by BIRC and by the investigator based on RECIST v1.1. PFS was estimated using the Kaplan-Meier method.

OS is defined as the time from the start date of study drug to the date of death due to any cause. If a patient did not have an event, OS was censored as defined in the statistical analysis plan. OS was estimated using the Kaplan-Meier method.

OIRR was calculated based on response assessments in the brain for participants having measurable or non-measurable brain metastases at baseline. OIRR is defined as the percentage of participants with a confirmed best overall intracranial response of CR or PR from the start of treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started) per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria as assessed by BIRC review.

IDCR is defined as the percentage of participants with a confirmed best overall intracranial response of CR or PR or SD (or non-CR/non-PD) per RANO-BM criteria as assessed by BIRC review.

TTIR is defined as the time from the start date of study drug to the date of the first documented intracranial response of either CR or PR per RANO-BM criteria as assessed by the BIRC review, which must be subsequently confirmed. If a patient did not have an event, TTIR was censored as defined in the statistical analysis plan. TTIR was estimated using the Kaplan-Meier method.

DOIR only applies to participants whose confirmed best overall intracranial response is CR or PR per RANO-BM criteria as assessed by the BIRC review. DOIR is defined as the time from the date of first documented intracranial response of either CR or PR to the date of the first documented intracranial progression per RANO-BM criteria as assessed by BIRC review or date of death due to any cause. If a patient did not have an event, DOIR was censored as defined in the statistical analysis plan. DOIR was estimated using the Kaplan-Meier method.

At Cycle 1 Day 1 (C1D1, pre-dose), blood samples were collected to investigate the association between Mesenchymal Epithelial Transition (MET) mutation status in baseline circulating tumor DNA (ctDNA) and capmatinib efficacy. These blood samples were tested for MET exon 14 (METex14) skipping mutations and classified as mutant or non-mutant. ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR). Tumor response was assessed by BIRC and by the investigator based on RECIST v1.1.

At Cycle 1 Day 1 (C1D1, pre-dose), blood samples were collected to investigate the association between MET mutation status in baseline ctDNA and capmatinib efficacy. These blood samples were tested for METex14 skipping mutations and classified as mutant or non-mutant. DOR only applies to patients whose best overall response is CR or PR based on BIRC assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response of CR or PR to the date of first documented progression or death due to any cause. If a patient did not have an event, DOR was censored as defined in the statistical analysis plan. DOR was estimated using the Kaplan-Meier method.

At Cycle 1 Day 1 (C1D1, pre-dose), blood samples were collected to investigate the association between MET mutation status in baseline ctDNA and capmatinib efficacy. These blood samples were tested for METex14 skipping mutations and classified as mutant or non-mutant. DOR only applies to patients whose best overall response is CR or PR based on investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response of CR or PR to the date of first documented progression or death due to any cause. If a patient did not have an event, DOR was censored as defined in the statistical analysis plan. DOR was estimated using the Kaplan-Meier method.

At Cycle 1 Day 1 (C1D1, pre-dose), blood samples were collected to investigate the association between MET mutation status in baseline ctDNA and capmatinib efficacy. These blood samples were tested for METex14 skipping mutations and classified as mutant or non-mutant. PFS is defined as the time from the start date of study drug to the date of the first radiologically documented PD or death due to any cause. If a patient did not have an event, PFS was censored as defined in the statistical analysis plan. Tumor response was assessed by BIRC and by the investigator based on RECIST v1.1. PFS was estimated using the Kaplan-Meier method.

Plasma capmatinib concentrations at steady state were quantified using a validated liquid chromatography tandem-mass spectrometry assay. Concentrations below the lower limit of quantification were treated as zero in the calculations. Pre-dose concentrations correspond to Ctrough, defined as the lowest plasma drug concentration observed immediately before the next dose.

Number of participants with AEs (any adverse events regardless of seriousness) and serious adverse events (SAEs), including changes in physical exams, electrocardiograms and laboratory results qualifying and reported as AEs. AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For CTCAE v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. The on-treatment period is defined from the day of first administration of study drug up to 30 days after the date of the last actual administration of study drug.

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items and is composed of both multi-item scales and single-item measures. These include 1 global health status/quality of life (QoL) scale, 5 functional scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All scales and single-item measures are scored from 0 to 100. This record summarizes the values of the global health status/QoL scale (0 to 100), where higher scores indicate better health/QoL. Therefore, a positive change from baseline is favorable.

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer Module 13 (EORTC QLQ-LC13) is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The 13 items of the LC13 include 1 multi-item scale (dyspnea) and 9 single items (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, and pain in other parts). Each item uses a 4-point Likert scale (1=not at all, 4=very much). Scores for both the dyspnea scale and single items are transformed to a 0-100 scale. This record summarizes the values of the dyspnea scale (0 to 100), where higher scores indicate greater symptom burden. Therefore, a negative change from baseline is a favorable outcome.

The EuroQol 5-Dimension 5-Level (EQ-5D-5L) is a standardized, generic instrument to measure health-related quality of life (HRQoL). It consists of two components: a descriptive system and a visual analogue scale. The descriptive system includes five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each rated on five levels of severity (1=no problems, 5=extreme problems). The EuroQol visual analogue scale (EQ VAS) is a 0-100 scale for self-rated overall health, where 0 represents the worst imaginable health and 100 the best imaginable health. This record summarizes the values of the EQ VAS (0 to 100), where higher scores indicate better health. Therefore, a positive change from baseline is favorable.

The National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy - Brain Symptom Index (NCCN FACT-FBrSI) was used to assess changes in symptoms potentially associated with brain metastases in this study. The NCCN FACT-FBrSI contains 24 items with a 7-day recall period and includes the following subscales: Disease-related symptoms - physical (12 items), Disease-related symptoms - emotional (5 items), Treatment side effects (5 items) and Function/well-being (2 items). Each item uses a 5-point Likert-type scale (0 = Not at all; 4 = Very much). Negatively worded items are reverse scored so that higher scores consistently indicate better symptom status and well-being. The total composite score is the sum of all 24 items and ranges from 0 to 96, with higher scores indicating better symptom status and well-being. An increase in the total composite score from baseline indicates a favorable outcome, while a decrease indicates an unfavorable outcome.

Deaths in the on-treatment period were recorded from the first dose of study treatment through 30 days after the last dose. Deaths in the survival follow-up period were recorded from 31 days after the last dose of study treatment until the end of the study. All deaths refers to the combined total of deaths occurring during the on-treatment period and the survival follow-up period. The exact duration of the on-treatment and survival follow-up periods varies by patient because treatment exposure differs. Consequently, a death occurring on the same study day (e.g., Day 350) may be classified as on-treatment for one patient and as survival follow-up for another who discontinued treatment earlier.