Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Non Small Cell Lung, Non Small Cell Lung Cancer, Non-small cell lung cancer, NSCLC, INC280, EGFR wild-type (wt), advanced non-small cell lung cancer, advanced/metastatic disease, Non-small cell lung carcinoma (NSCLC), treatment of lung cancer after first metastasis, lung cancer, lung adenocarcinoma, Non small cell lung carcinoma, MET exon 14 deletion, METex14del, MET exon 14 skipping, MET exon 14 mutation, MET mutation, MET amplification, MET inhibitor, MET dysregulation, MET activation, MET signaling, MET pathway, met, cMET, Geometry mono-1, Geometry
Brief summary
Study to evaluate the efficacy and safety of capmatinib as a single-agent treatment for subjects with advanced/metastatic (stage IIIB or IV) non-small cell lung cancer (NSCLC) who had wild-type epidermal growth factor receptor (EGFR wt) (for exon 19 deletions and exon 21 L858R substitution mutations), anaplastic lymphoma kinase (ALK)-negative rearrangement, and mesenchymal epithelial transition (MET) mutations leading to exon 14 deletion (referred to as MET mutation hereafter) and/or MET amplification.
Detailed description
This was a Phase II, multicenter, open-label study. Patients were enrolled in different cohorts based on their MET status (amplification and/or mutation) and prior treatment status: Cohort 1a, Cohort 1b, Cohort 2, Cohort 3, Cohort 4, Cohort 5a, Cohort 5b, Cohort 6, and Cohort 7. MET mutation (by RT-PCR) and/or MET amplification status by gene copy number (GCN, by FISH) was determined by central laboratory. Patients in Cohorts 1, 2, 3, and 4 had previously failed 1 or 2 prior lines of systemic therapy, while patients enrolled in Cohorts 5 and 7 were treatment-naïve for advanced disease/metastatic disease. Patients enrolled in Cohort 6 had failed 1 prior line of systemic therapy for advanced/ metastatic disease. Patients with MET mutation were enrolled in Cohort 4 (pre-treated), Cohort 5b (treatment naïve) or Cohort 7 (treatment naïve expansion cohort of Cohort 5b), irrespective of their MET GCN. The enrollment in expansion Cohort 7 started after the completion of enrollment in Cohort 5b. Patients without MET mutation, were enrolled in Cohorts 1a, 1b, 2, 3 (pre-treated) or 5a (treatment naïve), based on their MET GCN. Patients enrolled in Cohort 6 (expansion cohort of Cohort 1a and Cohort 4) had either MET GCN ≥10 without MET mutation (Cohort 6.1) or MET mutation, irrespective to their MET GCN (Cohort 6.2). The enrollment in Cohort 6 started upon enrollment completion of the respective Cohort 1a or Cohort 4. All participants in the study received oral capmatinib 400 mg twice daily. A treatment cycle was defined as 21 days. Treatment with capmatinib continued until patient experienced any of the following: disease progression according to RECIST 1.1 as determined by investigator and confirmed by Blinded Independent Review Committee (BIRC), unacceptable toxicity that precluded further treatment, treatment discontinuation at the discretion of the Investigator or patient, lost to follow-up, or death. Treatment with capmatinib was allowed beyond RECIST 1.1-defined disease progression (as determined by investigator and confirmed by BIRC) if, in the judgment of the investigator, there was evidence of clinical benefit and the patient wished to continue on the study treatment. All patients continued to have safety evaluations for 30 days after the last dose of study treatment. Patients who discontinued treatment with capmatinib for any reason other than disease progression, as determined by the investigator and confirmed by BIRC, death, withdrawal of consent for further assessments, or being lost to follow-up, continued to have tumor assessments (post-treatment efficacy follow-up) until disease progression confirmed by BIRC, death, withdrawal of consent for further assessments, or lost to follow-up. All patients who discontinued treatment with capmatinib were followed for survival (post-treatment survival follow-up) until death, loss to follow-up, withdrawal of consent to survival follow-up, or the end of the study.
Interventions
DRUGCapmatinib
Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. Capmatinib was administered to participants in Cohorts 1a, 1b, 2, 3, 4, 5a and 5b in a fasted state. For Cohorts 6.1. 6.2 and 7, capmatinib was administered either with or without food.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Subjects with Stage IIIB or IV NSCLC (any histology) at the time of study entry * Subjects with histologically or cytologically confirmed diagnosis of NSCLC that is: 1. EGFR wt status (for exon 19 deletions and exon 21 L858R substitution mutations) 2. and ALK rearrangement-negative 3. and MET-mutation and/or amplification status (as defined in the protocol). * For Cohorts 1a, 1b, 2, 3, 4 subjects must have failed one or two prior lines of systemic therapy for advanced disease (stage IIIB or IV NSCLC). For Cohort 6, subjects must have failed one prior line of systemic therapy for advanced disease (stage IIIB or IV NSCLC). * For Cohorts 5a, 5b, and 7, subjects must not have received any systemic therapy for advanced disease (stage IIIB or IV NSCLC). * Subjects with at least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there was clear sign of progression since the irradiation. * Subjects who recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (Common Terminology Criteria for Adverse Events \[CTCAE\] v 4.03). Subjects with any grade of alopecia were allowed to enter the study. * Subjects with adequate organ function * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 Key
Exclusion criteria
* Prior treatment with crizotinib, or any other MET or HGF inhibitor * Characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations. * Characterized ALK-positive rearrangement. * Symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms. * Clinically significant, uncontrolled heart diseases * Thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting capmatinib or subjects who had not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy ≤ 2 weeks prior to starting capmatinib or subjects who had not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting capmatinib was allowed. * Receiving treatment with strong inducers of CYP3A4 and/or any enzyme-inducing anticonvulsant and could not be discontinued ≥ 1 week prior to the start of treatment with capmatinib and for the duration of the study. * Receiving treatment with unstable or increasing doses of corticosteroids. * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of capmatinib. * Applicable to Cohorts 1-4 and Cohort 6 only: previous anticancer and investigational agents within 4 weeks or ≤ 5 × half-life of the agent (whichever was longer) before first dose of- capmatinib. If previous treatment was a monoclonal antibody, then the treatment must have been discontinued ≥ 4 weeks before first dose of capmatinib. If previous treatment was an oral targeted agent, then the treatment must have been discontinued ≥ 5 × half-life of the agent before the first dose of capmatinib. * Pregnant or nursing (lactating) women. * Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 7 days after stopping treatment * Sexually active males unless they used a condom during intercourse while taking drug and for 7 days after stopping treatment and should not father a child in this period. * 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | Up to approximately 5 years | Percentage of participants with a best overall response defined as confirmed complete response (CR) or partial response (PR) by BIRC assessment per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR by Investigator Assessment | Up to approximately 5 years | Percentage of patients with a best overall response defined as confirmed CR or PR per RECIST 1.1 by investigator assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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 by Investigator Assessment | Up to approximately 5 years | Time from the date of the first documented CR or PR per RECIST 1.1 by investigator assessment to the first documented progression or death due to any cause for patients with confirmed PR or CR. The Kaplan-Meier method was used to estimate DOR, and the median DOR, along with 95% confidence intervals was reported. If a subject did not have an event, DOR was censored at the date of last adequate tumor assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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. |
| Time to Response (TTR) by BIRC Assessment | Up to approximately 5 years | Time between date of start of treatment until first documented response (confirmed CR or PR) per RECIST 1.1 by BIRC assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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. |
| TTR by Investigator Assessment | Up to approximately 5 years | Time between date of start of treatment until first documented response (confirmed CR or PR) per RECIST 1.1 by investigator assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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. |
| Disease Control Rate (DCR) | Up to approximately 5 years | Percentage of participants with a best overall response of confirmed CR, PR or stable disease (SD) per RECIST 1.1 by BIRC and investigator assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease. |
| Progression-Free Survival | Up to approximately 5 years | Time from start of treatment to the date of the first documented progression or death due to any cause per RECIST 1.1 by BIRC and investigator assessment. Clinical deterioration was not considered as a qualifying event for progression. PFS was censored at the last adequate tumor assessment if one of the following occurred: absence of event or the event occurred after two or more missing tumor assessments. The Kaplan-Meier method was used to estimate PFS, and the median PFS, along with 95% confidence intervals, was reported. Progressive disease: For target lesions, 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. For non-target lesions, unequivocal progression of existing non-target lesions |
| Overall Survival (OS) | Up to approximately 6 years | Time from start of treatment to the date of death due to any cause. If the patient was alive at the date of the analysis cut-off or lost to follow-up, then OS was censored at the last contact date prior to data cut-off date. The Kaplan-Meier method was used to estimate OS, and the median OS, along with 95% confidence intervals, was reported. |
| Pharmacokinetic (PK) Concentrations of Capmatinib | Cycle (C) 1 Day (D) 1 predose and 2 hours post-dose, C1D15 pre-dose and 2 hours post-dose, C3D1 pre-dose. Each Cycle is 21 days | PK concentrations of capmatinib. Plasma concentrations of capmatinib were measured using validated liquid chromatography-tandem mass spectrometry (LCMS/MS) methods with a lower limit of quantification (LLOQ) of approximately 1.0 ng/mL. Capmatinib concentration data was summarized for Cohorts 1a, 1b, 2, 3, 4, 5a and 5b when capmatinib was administered in fasted state; and for Cohorts 6 and 7 when capmatinib was administered with or without food. |
| Duration of Response (DOR) by BIRC Assessment | Up to approximately 5 years | Time from the date of the first documented CR or PR by BIRC per RECIST 1.1 to the first documented progression or date of death due to any cause for patients with confirmed PR or CR. The Kaplan-Meier method was used to estimate DOR, and the median DOR, along with 95% confidence intervals was reported. If a subject did not have an event, DOR was censored at the date of last adequate tumor assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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. |
| Maximum Concentration (Cmax) of CMN288 | Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days | Cmax of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis |
| Area Under the Plasma Concentration-time Curve From Zero to Time Infinity (AUCinf) of Capmatinib | Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days | AUCinf of capmatinib was estimated by non-compartmental analysis. AUCinf is the area under the plasma concentration-time curve extrapolated to infinity. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis |
| Area Under the Plasma Concentration-time Curve From Zero to Time Infinity (AUCinf) of CMN288 | Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days | AUCinf of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. AUCinf is the area under the plasma concentration-time curve extrapolated to infinity. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis |
| Time to Reach Maximum Concentration (Tmax) of Capmatinib | Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days | Tmax of capmatinib was estimated by non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis |
| Time to Reach Maximum Concentration (Tmax) of CMN288 | Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days | Tmax of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from cohorts 1-5, who had an extensive PK collection schedule, were included in this analysis |
| Elimination Half-life (T1/2) of Capmatinib | Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days | T1/2 of capmatinib was estimated by non-compartmental analysis. T1/2 is the time it takes for the concentration of capmatinib in the bloodstream to decrease by half. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis |
| Elimination Half-life (T1/2) of CMN288 | Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days | T1/2 of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. T1/2 is the time it takes for the concentration of CMN288 in the bloodstream to decrease by half. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis |
| Maximum Concentration (Cmax) of Capmatinib | Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days | Cmax of capmatinib was estimated by non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis |
Countries
Argentina, Austria, Belgium, France, Germany, Israel, Italy, Japan, Lebanon, Mexico, Netherlands, Norway, Russia, Singapore, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled in 95 centers across 20 countries
Pre-assignment details
Screening assessments were conducted up to 28 days prior to the start of study treatment
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L) | 69 |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Pre-treated patients with MET GCN ≥ 6 and \< 10 treated with INC280 at 400 mg BID as second or third line (2/3L) | 42 |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Pre-treated patients with MET GCN ≥ 4 and \< 6 treated with INC280 at 400mg BID as second or third line (2/3L) | 54 |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Pre-treated patients with MET GCN \< 4 treated with INC280 at 400mg BID as second or third line (2/3L) | 30 |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L) | 69 |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L) | 15 |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) | 28 |
| Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a) | 3 |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4) | 31 |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b) | 32 |
| Total | 373 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Post-treatment Efficacy Follow-up | Adverse Event | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Post-treatment Efficacy Follow-up | Death | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Post-treatment Efficacy Follow-up | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Post-treatment Efficacy Follow-up | Physician Decision | 4 | 2 | 4 | 2 | 4 | 0 | 1 | 0 | 0 | 1 |
| Post-treatment Efficacy Follow-up | Progressive disease | 6 | 5 | 9 | 5 | 15 | 4 | 5 | 1 | 3 | 3 |
| Post-treatment Efficacy Follow-up | Study terminated by sponsor | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Post-treatment Efficacy Follow-up | Subject/guardian decision | 4 | 2 | 3 | 1 | 1 | 1 | 0 | 0 | 0 | 2 |
| Treatment Period | Adverse Event | 11 | 6 | 8 | 5 | 14 | 3 | 6 | 1 | 6 | 8 |
| Treatment Period | Death | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment Period | Physician Decision | 5 | 4 | 6 | 1 | 4 | 0 | 2 | 0 | 1 | 4 |
| Treatment Period | Progressive disease | 48 | 31 | 37 | 21 | 43 | 12 | 16 | 2 | 20 | 14 |
| Treatment Period | Protocol deviation | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Study terminated (as per protocol) by Sponsor | 0 | 0 | 0 | 0 | 3 | 0 | 2 | 0 | 3 | 4 |
| Treatment Period | Subject/Guardian decision | 5 | 1 | 1 | 2 | 5 | 0 | 2 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Total | Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) | Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.9 Years STANDARD_DEVIATION 9.56 | 65.7 Years STANDARD_DEVIATION 10.18 | 73.3 Years STANDARD_DEVIATION 8.35 | 69.0 Years STANDARD_DEVIATION 6.29 | 60.7 Years STANDARD_DEVIATION 10.69 | 72.4 Years STANDARD_DEVIATION 7.02 | 68.2 Years STANDARD_DEVIATION 10.36 | 71.0 Years STANDARD_DEVIATION 8.32 | 61.7 Years STANDARD_DEVIATION 9.23 | 61.7 Years STANDARD_DEVIATION 10 | 59.5 Years STANDARD_DEVIATION 9.11 |
| Race/Ethnicity, Customized Asian | 17 Participants | 84 Participants | 3 Participants | 5 Participants | 1 Participants | 4 Participants | 6 Participants | 19 Participants | 11 Participants | 14 Participants | 4 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 51 Participants | 281 Participants | 26 Participants | 24 Participants | 1 Participants | 24 Participants | 9 Participants | 49 Participants | 19 Participants | 40 Participants | 38 Participants |
| Race/Ethnicity, Customized Native American | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 15 Participants | 164 Participants | 23 Participants | 16 Participants | 1 Participants | 18 Participants | 4 Participants | 40 Participants | 11 Participants | 15 Participants | 21 Participants |
| Sex: Female, Male Male | 54 Participants | 209 Participants | 9 Participants | 15 Participants | 2 Participants | 10 Participants | 11 Participants | 29 Participants | 19 Participants | 39 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 10 / 69 | 7 / 42 | 12 / 54 | 4 / 30 | 14 / 69 | 0 / 15 | 5 / 28 | 1 / 3 | 5 / 31 | 5 / 32 | 19 / 100 | 10 / 60 | 63 / 373 | 44 / 59 | 26 / 35 | 34 / 42 | 22 / 25 | 44 / 55 | 13 / 15 | 13 / 20 | 2 / 2 | 17 / 20 | 16 / 23 | 61 / 75 | 29 / 43 | 231 / 296 |
| other Total, other adverse events | 66 / 69 | 41 / 42 | 53 / 54 | 28 / 30 | 66 / 69 | 15 / 15 | 28 / 28 | 3 / 3 | 29 / 31 | 31 / 32 | 95 / 100 | 59 / 60 | 360 / 373 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 42 / 69 | 21 / 42 | 30 / 54 | 15 / 30 | 38 / 69 | 9 / 15 | 14 / 28 | 2 / 3 | 14 / 31 | 17 / 32 | 52 / 100 | 31 / 60 | 202 / 373 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment
Percentage of participants with a best overall response defined as confirmed complete response (CR) or partial response (PR) by BIRC assessment per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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.
Time frame: Up to approximately 5 years
Population: Full Analysis Set (FAS)-including all subjects who received at least one dose of capmatinib
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 29.0 Percentage of Participants |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 11.9 Percentage of Participants |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 9.3 Percentage of Participants |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 6.7 Percentage of Participants |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 40.6 Percentage of Participants |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 40.0 Percentage of Participants |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 67.9 Percentage of Participants |
| Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 0.0 Percentage of Participants |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 51.6 Percentage of Participants |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 68.8 Percentage of Participants |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 44.0 Percentage of Participants |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment | 68.3 Percentage of Participants |
Secondary
Area Under the Plasma Concentration-time Curve From Zero to Time Infinity (AUCinf) of Capmatinib
AUCinf of capmatinib was estimated by non-compartmental analysis. AUCinf is the area under the plasma concentration-time curve extrapolated to infinity. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time frame: Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Population: Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (AUCinf for capmatinib) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Area Under the Plasma Concentration-time Curve From Zero to Time Infinity (AUCinf) of Capmatinib | 17000 nanogram * hour / mililiter (ng*h/ml) | Standard Deviation 7770 |
Secondary
Area Under the Plasma Concentration-time Curve From Zero to Time Infinity (AUCinf) of CMN288
AUCinf of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. AUCinf is the area under the plasma concentration-time curve extrapolated to infinity. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time frame: Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Population: Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (AUCinf for CMN288) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Area Under the Plasma Concentration-time Curve From Zero to Time Infinity (AUCinf) of CMN288 | 9020 ng*h/ml | Standard Deviation 5060 |
Secondary
Disease Control Rate (DCR)
Percentage of participants with a best overall response of confirmed CR, PR or stable disease (SD) per RECIST 1.1 by BIRC and investigator assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Time frame: Up to approximately 5 years
Population: FAS, including all subjects who received at least one dose of capmatinib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Disease Control Rate (DCR) | By investigator assessment | 60.9 Percentage of participants |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Disease Control Rate (DCR) | By BIRC assessment | 71.0 Percentage of participants |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Disease Control Rate (DCR) | By BIRC assessment | 54.8 Percentage of participants |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Disease Control Rate (DCR) | By investigator assessment | 45.2 Percentage of participants |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | Disease Control Rate (DCR) | By BIRC assessment | 46.3 Percentage of participants |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | Disease Control Rate (DCR) | By investigator assessment | 44.4 Percentage of participants |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | Disease Control Rate (DCR) | By investigator assessment | 46.7 Percentage of participants |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | Disease Control Rate (DCR) | By BIRC assessment | 53.3 Percentage of participants |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Disease Control Rate (DCR) | By BIRC assessment | 78.3 Percentage of participants |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Disease Control Rate (DCR) | By investigator assessment | 76.8 Percentage of participants |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | Disease Control Rate (DCR) | By BIRC assessment | 66.7 Percentage of participants |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | Disease Control Rate (DCR) | By investigator assessment | 73.3 Percentage of participants |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | Disease Control Rate (DCR) | By BIRC assessment | 96.4 Percentage of participants |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | Disease Control Rate (DCR) | By investigator assessment | 96.4 Percentage of participants |
| Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) | Disease Control Rate (DCR) | By BIRC assessment | 100.0 Percentage of participants |
| Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) | Disease Control Rate (DCR) | By investigator assessment | 100.0 Percentage of participants |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | Disease Control Rate (DCR) | By investigator assessment | 90.3 Percentage of participants |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | Disease Control Rate (DCR) | By BIRC assessment | 90.3 Percentage of participants |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | Disease Control Rate (DCR) | By BIRC assessment | 100.0 Percentage of participants |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | Disease Control Rate (DCR) | By investigator assessment | 96.9 Percentage of participants |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Disease Control Rate (DCR) | By BIRC assessment | 82.0 Percentage of participants |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Disease Control Rate (DCR) | By investigator assessment | 81.0 Percentage of participants |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | Disease Control Rate (DCR) | By investigator assessment | 96.7 Percentage of participants |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | Disease Control Rate (DCR) | By BIRC assessment | 98.3 Percentage of participants |
Secondary
DOR by Investigator Assessment
Time from the date of the first documented CR or PR per RECIST 1.1 by investigator assessment to the first documented progression or death due to any cause for patients with confirmed PR or CR. The Kaplan-Meier method was used to estimate DOR, and the median DOR, along with 95% confidence intervals was reported. If a subject did not have an event, DOR was censored at the date of last adequate tumor assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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.
Time frame: Up to approximately 5 years
Population: Participants with confirmed CR or PR by investigator assessment in FAS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | DOR by Investigator Assessment | 6.80 Months |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | DOR by Investigator Assessment | 6.93 Months |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | DOR by Investigator Assessment | 19.48 Months |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | DOR by Investigator Assessment | 6.93 Months |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | DOR by Investigator Assessment | 8.31 Months |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | DOR by Investigator Assessment | 9.66 Months |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | DOR by Investigator Assessment | 13.83 Months |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | DOR by Investigator Assessment | 14.57 Months |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | DOR by Investigator Assessment | 15.21 Months |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | DOR by Investigator Assessment | 8.38 Months |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | DOR by Investigator Assessment | 13.96 Months |
Secondary
Duration of Response (DOR) by BIRC Assessment
Time from the date of the first documented CR or PR by BIRC per RECIST 1.1 to the first documented progression or date of death due to any cause for patients with confirmed PR or CR. The Kaplan-Meier method was used to estimate DOR, and the median DOR, along with 95% confidence intervals was reported. If a subject did not have an event, DOR was censored at the date of last adequate tumor assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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.
Time frame: Up to approximately 5 years
Population: Participants with confirmed CR or PR by BIRC in FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Duration of Response (DOR) by BIRC Assessment | 8.31 Months |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Duration of Response (DOR) by BIRC Assessment | 24.94 Months |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | Duration of Response (DOR) by BIRC Assessment | 9.66 Months |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | Duration of Response (DOR) by BIRC Assessment | 4.19 Months |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Duration of Response (DOR) by BIRC Assessment | 9.72 Months |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | Duration of Response (DOR) by BIRC Assessment | 7.54 Months |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | Duration of Response (DOR) by BIRC Assessment | 12.58 Months |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | Duration of Response (DOR) by BIRC Assessment | 9.05 Months |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | Duration of Response (DOR) by BIRC Assessment | 16.59 Months |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Duration of Response (DOR) by BIRC Assessment | 9.72 Months |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | Duration of Response (DOR) by BIRC Assessment | 16.59 Months |
Secondary
Elimination Half-life (T1/2) of Capmatinib
T1/2 of capmatinib was estimated by non-compartmental analysis. T1/2 is the time it takes for the concentration of capmatinib in the bloodstream to decrease by half. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time frame: Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Population: Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (T1/2 for capmatinib) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Elimination Half-life (T1/2) of Capmatinib | Cycle 1 Day 1 | 1.87 hour | Standard Deviation 0.947 |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Elimination Half-life (T1/2) of Capmatinib | Cycle 1 Day 15 | 2.40 hour | Standard Deviation 0.652 |
Secondary
Elimination Half-life (T1/2) of CMN288
T1/2 of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. T1/2 is the time it takes for the concentration of CMN288 in the bloodstream to decrease by half. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time frame: Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Population: Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (T1/2 for CMN288) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Elimination Half-life (T1/2) of CMN288 | Cycle 1 Day 1 | 3.14 hour | Standard Deviation 1.42 |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Elimination Half-life (T1/2) of CMN288 | Cycle 1 Day 15 | 3.06 hour | Standard Deviation 0.949 |
Secondary
Maximum Concentration (Cmax) of Capmatinib
Cmax of capmatinib was estimated by non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time frame: Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Population: Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (Cmax for capmatinib) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Maximum Concentration (Cmax) of Capmatinib | Cycle 1 Day 1 | 4230 ng/ml | Standard Deviation 2290 |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Maximum Concentration (Cmax) of Capmatinib | Cycle 1 Day 15 | 5450 ng/ml | Standard Deviation 2560 |
Secondary
Maximum Concentration (Cmax) of CMN288
Cmax of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time frame: Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Population: Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (Cmax for CMN288) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Maximum Concentration (Cmax) of CMN288 | Cycle 1 Day 1 | 1910 ng/ml | Standard Deviation 1420 |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Maximum Concentration (Cmax) of CMN288 | Cycle 1 Day 15 | 1420 ng/ml | Standard Deviation 725 |
Secondary
ORR by Investigator Assessment
Percentage of patients with a best overall response defined as confirmed CR or PR per RECIST 1.1 by investigator assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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.
Time frame: Up to approximately 5 years
Population: FAS, including all subjects who received at least one dose of capmatinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | ORR by Investigator Assessment | 27.5 Percentage of participants |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | ORR by Investigator Assessment | 7.1 Percentage of participants |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | ORR by Investigator Assessment | 9.3 Percentage of participants |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | ORR by Investigator Assessment | 3.3 Percentage of participants |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | ORR by Investigator Assessment | 43.5 Percentage of participants |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | ORR by Investigator Assessment | 40.0 Percentage of participants |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | ORR by Investigator Assessment | 60.7 Percentage of participants |
| Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) | ORR by Investigator Assessment | 0.0 Percentage of participants |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | ORR by Investigator Assessment | 45.2 Percentage of participants |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | ORR by Investigator Assessment | 56.3 Percentage of participants |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | ORR by Investigator Assessment | 44.0 Percentage of participants |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | ORR by Investigator Assessment | 58.3 Percentage of participants |
Secondary
Overall Survival (OS)
Time from start of treatment to the date of death due to any cause. If the patient was alive at the date of the analysis cut-off or lost to follow-up, then OS was censored at the last contact date prior to data cut-off date. The Kaplan-Meier method was used to estimate OS, and the median OS, along with 95% confidence intervals, was reported.
Time frame: Up to approximately 6 years
Population: FAS, including all subjects who received at least one dose of capmatinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Overall Survival (OS) | 10.61 Months |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Overall Survival (OS) | 7.46 Months |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | Overall Survival (OS) | 10.15 Months |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | Overall Survival (OS) | 9.46 Months |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Overall Survival (OS) | 13.57 Months |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | Overall Survival (OS) | 9.56 Months |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | Overall Survival (OS) | 20.76 Months |
| Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) | Overall Survival (OS) | 4.14 Months |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | Overall Survival (OS) | 25.95 Months |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | Overall Survival (OS) | 21.36 Months |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Overall Survival (OS) | 16.79 Months |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | Overall Survival (OS) | 21.36 Months |
Secondary
Pharmacokinetic (PK) Concentrations of Capmatinib
PK concentrations of capmatinib. Plasma concentrations of capmatinib were measured using validated liquid chromatography-tandem mass spectrometry (LCMS/MS) methods with a lower limit of quantification (LLOQ) of approximately 1.0 ng/mL. Capmatinib concentration data was summarized for Cohorts 1a, 1b, 2, 3, 4, 5a and 5b when capmatinib was administered in fasted state; and for Cohorts 6 and 7 when capmatinib was administered with or without food.
Time frame: Cycle (C) 1 Day (D) 1 predose and 2 hours post-dose, C1D15 pre-dose and 2 hours post-dose, C3D1 pre-dose. Each Cycle is 21 days
Population: Participants who received at least one dose of capmatinib and provided at least one evaluable pharmacokinetic concentration for capmatinib at the specified time points. Participants who received capmatinib under the same administration conditions (fasted state or with/without food) were pooled together.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Pharmacokinetic (PK) Concentrations of Capmatinib | Cycle 1 Day 1- 2 hours post-dose | 3360 nanogram/mililiter (ng/ml) | Standard Deviation 1920 |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Pharmacokinetic (PK) Concentrations of Capmatinib | Cycle 1 Day 15- 2 hours post-dose | 4100 nanogram/mililiter (ng/ml) | Standard Deviation 2100 |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Pharmacokinetic (PK) Concentrations of Capmatinib | Cycle 1 Day 15 - pre-dose | 727 nanogram/mililiter (ng/ml) | Standard Deviation 781 |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Pharmacokinetic (PK) Concentrations of Capmatinib | Cycle 3 Day 1 - pre-dose | 687 nanogram/mililiter (ng/ml) | Standard Deviation 1000 |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Pharmacokinetic (PK) Concentrations of Capmatinib | Cycle 1 Day 1- pre-dose | 0.00 nanogram/mililiter (ng/ml) | Standard Deviation 0 |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Pharmacokinetic (PK) Concentrations of Capmatinib | Cycle 3 Day 1 - pre-dose | 672 nanogram/mililiter (ng/ml) | Standard Deviation 745 |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Pharmacokinetic (PK) Concentrations of Capmatinib | Cycle 1 Day 1- pre-dose | 0.00 nanogram/mililiter (ng/ml) | Standard Deviation 0 |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Pharmacokinetic (PK) Concentrations of Capmatinib | Cycle 1 Day 1- 2 hours post-dose | 3060 nanogram/mililiter (ng/ml) | Standard Deviation 1780 |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Pharmacokinetic (PK) Concentrations of Capmatinib | Cycle 1 Day 15 - pre-dose | 663 nanogram/mililiter (ng/ml) | Standard Deviation 806 |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Pharmacokinetic (PK) Concentrations of Capmatinib | Cycle 1 Day 15- 2 hours post-dose | 4340 nanogram/mililiter (ng/ml) | Standard Deviation 2000 |
Secondary
Progression-Free Survival
Time from start of treatment to the date of the first documented progression or death due to any cause per RECIST 1.1 by BIRC and investigator assessment. Clinical deterioration was not considered as a qualifying event for progression. PFS was censored at the last adequate tumor assessment if one of the following occurred: absence of event or the event occurred after two or more missing tumor assessments. The Kaplan-Meier method was used to estimate PFS, and the median PFS, along with 95% confidence intervals, was reported. Progressive disease: For target lesions, 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. For non-target lesions, unequivocal progression of existing non-target lesions
Time frame: Up to approximately 5 years
Population: FAS, including all subjects who received at least one dose of capmatinib.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Progression-Free Survival | By BIRC assessment | 4.07 Months |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Progression-Free Survival | By investigator assessment | 4.14 Months |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Progression-Free Survival | By BIRC assessment | 2.66 Months |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Progression-Free Survival | By investigator assessment | 2.40 Months |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | Progression-Free Survival | By BIRC assessment | 2.66 Months |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | Progression-Free Survival | By investigator assessment | 2.60 Months |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | Progression-Free Survival | By BIRC assessment | 3.55 Months |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | Progression-Free Survival | By investigator assessment | 2.73 Months |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Progression-Free Survival | By investigator assessment | 4.80 Months |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Progression-Free Survival | By BIRC assessment | 5.42 Months |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | Progression-Free Survival | By BIRC assessment | 4.17 Months |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | Progression-Free Survival | By investigator assessment | 2.76 Months |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | Progression-Free Survival | By investigator assessment | 11.99 Months |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | Progression-Free Survival | By BIRC assessment | 12.42 Months |
| Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) | Progression-Free Survival | By BIRC assessment | 2.79 Months |
| Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) | Progression-Free Survival | By investigator assessment | 2.76 Months |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | Progression-Free Survival | By BIRC assessment | 6.93 Months |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | Progression-Free Survival | By investigator assessment | 6.90 Months |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | Progression-Free Survival | By BIRC assessment | 12.45 Months |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | Progression-Free Survival | By investigator assessment | 9.79 Months |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Progression-Free Survival | By investigator assessment | 6.60 Months |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Progression-Free Survival | By BIRC assessment | 5.49 Months |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | Progression-Free Survival | By investigator assessment | 11.07 Months |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | Progression-Free Survival | By BIRC assessment | 12.45 Months |
Secondary
Time to Reach Maximum Concentration (Tmax) of Capmatinib
Tmax of capmatinib was estimated by non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time frame: Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Population: Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (Tmax for capmatinib) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Time to Reach Maximum Concentration (Tmax) of Capmatinib | Cycle 1 Day 1 | 1.87 hour |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Time to Reach Maximum Concentration (Tmax) of Capmatinib | Cycle 1 Day 15 | 1.09 hour |
Secondary
Time to Reach Maximum Concentration (Tmax) of CMN288
Tmax of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL. Only a subset of participants from cohorts 1-5, who had an extensive PK collection schedule, were included in this analysis
Time frame: Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Population: Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (Tmax for CMN288) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Time to Reach Maximum Concentration (Tmax) of CMN288 | Cycle 1 Day 1 | 1.93 hour |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Time to Reach Maximum Concentration (Tmax) of CMN288 | Cycle 1 Day 15 | 1.91 hour |
Secondary
Time to Response (TTR) by BIRC Assessment
Time between date of start of treatment until first documented response (confirmed CR or PR) per RECIST 1.1 by BIRC assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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.
Time frame: Up to approximately 5 years
Population: Participants with confirmed CR or PR by BIRC in FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | Time to Response (TTR) by BIRC Assessment | 1.4 Months |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | Time to Response (TTR) by BIRC Assessment | 2.8 Months |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | Time to Response (TTR) by BIRC Assessment | 1.4 Months |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | Time to Response (TTR) by BIRC Assessment | 3.4 Months |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Time to Response (TTR) by BIRC Assessment | 1.4 Months |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | Time to Response (TTR) by BIRC Assessment | 1.4 Months |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | Time to Response (TTR) by BIRC Assessment | 1.4 Months |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | Time to Response (TTR) by BIRC Assessment | 1.4 Months |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | Time to Response (TTR) by BIRC Assessment | 1.4 Months |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | Time to Response (TTR) by BIRC Assessment | 1.4 Months |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | Time to Response (TTR) by BIRC Assessment | 1.4 Months |
Secondary
TTR by Investigator Assessment
Time between date of start of treatment until first documented response (confirmed CR or PR) per RECIST 1.1 by investigator assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-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.
Time frame: Up to approximately 5 years
Population: Participants with confirmed CR or PR by investigator assessment in FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | TTR by Investigator Assessment | 1.4 Months |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | TTR by Investigator Assessment | 1.4 Months |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | TTR by Investigator Assessment | 1.3 Months |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | TTR by Investigator Assessment | 1.3 Months |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | TTR by Investigator Assessment | 1.4 Months |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | TTR by Investigator Assessment | 1.4 Months |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | TTR by Investigator Assessment | 1.4 Months |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | TTR by Investigator Assessment | 1.4 Months |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | TTR by Investigator Assessment | 1.4 Months |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | TTR by Investigator Assessment | 1.4 Months |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | TTR by Investigator Assessment | 1.4 Months |
Post Hoc
All Collected Deaths
On-treatment deaths were collected from start of treatment to 30 days after last dose of treatment. Post-treatment efficacy/survival follow-up deaths were collected from 31 days after last dose of treatment until the end of the study. All deaths refer to the sum of on-treatment and post-treatment efficacy/survival follow-up deaths.
Time frame: On-treatment: Up to approximately 5.5 years. Post-treatment efficacy/survival follow-up: Up to approximately 6 years
Population: FAS, including all subjects who received at least one dose of capmatinib
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | All Collected Deaths | All deaths | 54 Participants |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | All Collected Deaths | On-treatment | 10 Participants |
| Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 44 Participants |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | All Collected Deaths | All deaths | 33 Participants |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 26 Participants |
| Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) | All Collected Deaths | On-treatment | 7 Participants |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 34 Participants |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | All Collected Deaths | On-treatment | 12 Participants |
| Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) | All Collected Deaths | All deaths | 46 Participants |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | All Collected Deaths | On-treatment | 4 Participants |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | All Collected Deaths | All deaths | 26 Participants |
| Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 22 Participants |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 44 Participants |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | All Collected Deaths | On-treatment | 14 Participants |
| Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | All Collected Deaths | All deaths | 58 Participants |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | All Collected Deaths | All deaths | 13 Participants |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | All Collected Deaths | On-treatment | 0 Participants |
| Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 13 Participants |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 13 Participants |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | All Collected Deaths | On-treatment | 5 Participants |
| Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) | All Collected Deaths | All deaths | 18 Participants |
| Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) | All Collected Deaths | On-treatment | 1 Participants |
| Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 2 Participants |
| Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) | All Collected Deaths | All deaths | 3 Participants |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | All Collected Deaths | On-treatment | 5 Participants |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 17 Participants |
| Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) | All Collected Deaths | All deaths | 22 Participants |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 16 Participants |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | All Collected Deaths | All deaths | 21 Participants |
| Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) | All Collected Deaths | On-treatment | 5 Participants |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 61 Participants |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | All Collected Deaths | On-treatment | 19 Participants |
| Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) | All Collected Deaths | All deaths | 80 Participants |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | All Collected Deaths | On-treatment | 10 Participants |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | All Collected Deaths | All deaths | 39 Participants |
| Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) | All Collected Deaths | Post-treatment efficacy/survival follow-up | 29 Participants |
| All Participants | All Collected Deaths | All deaths | 294 Participants |
| All Participants | All Collected Deaths | Post-treatment efficacy/survival follow-up | 231 Participants |
| All Participants | All Collected Deaths | On-treatment | 63 Participants |