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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04139317
Registration number
NCT04139317
Ethics application status
Date submitted
14/10/2019
Date registered
25/10/2019
Titles & IDs
Public title
Safety and Efficacy of Capmatinib (INC280) Plus Pembrolizumab vs Pembrolizumab Alone in NSCLC With PD-L1= 50%
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Scientific title
A Randomized, Open Label, Multicenter Phase II Study Evaluating the Efficacy and Safety of Capmatinib (INC280) Plus Pembrolizumab Versus Pembrolizumab Alone as First Line Treatment for Locally Advanced or Metastatic Non-small Cell Lung Cancer With PD-L1= 50%
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Secondary ID [1]
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2019-002660-27
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Secondary ID [2]
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CINC280I12201
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer (NSCLC)
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Condition category
Condition code
Cancer
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Lung - Mesothelioma
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Cancer
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Lung - Non small cell
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Cancer
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Lung - Small cell
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Capmatinib
Treatment: Other - Pembrolizumab
Experimental: Capmatinib 400mg BID + pembrolizumab 200mg Q3W - Capmatinib (INC280) 400 mg orally twice daily (BID) in combination with pembrolizumab 200 mg intravenously every 3 weeks (Q3W)
Active comparator: Pembrolizumab 200mg Q3W - Pembrolizumab 200 mg intravenously every 3 weeks (Q3W)
Treatment: Drugs: Capmatinib
INC280 tablets were administered orally at 400 mg on a continuous twice daily (BID) dosing schedule, from Day 1 until Day 21 of each 21-day cycle.
Treatment: Other: Pembrolizumab
Pembrolizumab was administered by intravenous infusion at 200 mg once every 3 weeks (Q3W).
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Treatment: Other
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Progression-Free Survival (PFS) by Investigator Assessment as Per RECIST 1.1
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Assessment method [1]
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PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. Tumor response was based on investigator assessment per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment, the start of a subsequent anti-neoplastic therapy (if any) or the date of sponsor's decision to discontinue capmatinib (applicable only to subjects on the combination arm).
Due to the discontinuation of one of the investigational drugs (capmatinib) in all subjects in the combination arm, PFS was censored on the 21-Jan-2021 or the last adequate tumor assessment prior to that date for the capmatinib plus pembrolizumab arm.
PFS was analyzed using Kaplan-Meier estimates.
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Timepoint [1]
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Up to 1.3 years
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Secondary outcome [1]
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Overall Response Rate (ORR) by Investigator Assessment as Per RECIST 1.1
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Assessment method [1]
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Tumor response was based on local investigator assessment as RECIST v1.1. ORR per RECIST v1.1 is defined as the percentage of participants with a best overall response (BOR) of Complete Response (CR) or Partial Response (PR). For the capmatinib plus pembrolizumab arm, 21-Jan-2021 or any last adequate tumor assessment prior to that date was considered as the end of evaluation period for BOR.
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.
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Timepoint [1]
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Up to 1.3 years
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Secondary outcome [2]
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Disease Control Rate (DCR) by Investigator Assessment as Per RECIST 1.1
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Assessment method [2]
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Tumor response was based on local investigator assessment per RECIST v1.1. DCR is defined as the percentage of participants with a BOR of Complete Response (CR), Partial Response (PR), Stable Disease (SD), and non-CR/non-progressive disease (for subjects without target lesions). For the capmatinib plus pembrolizumab arm, 21-Jan-2021 or any last adequate tumor assessment prior to that date was considered as the end of evaluation period for BOR.
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; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression).
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Timepoint [2]
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Up to 1.3 years
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Secondary outcome [3]
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Time to Response (TTR) by Investigator Assessment as Per RECIST 1.1
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Assessment method [3]
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TTR is defined as the time from the date of randomization to the first documented response of either complete response or partial response, which must be subsequently confirmed (although initial date of response is used, not date of confirmation).
TTR was analyzed using the Kaplan-Meier method as defined in the statistical analysis plan.
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Timepoint [3]
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Up to 1.3 years
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Secondary outcome [4]
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Duration of Response (DOR) by Investigator Assessment as Per RECIST 1.1
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Assessment method [4]
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DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment of overall lesion response according to RECIST v1.1. DOR is defined as the time from the date of first documented response (confirmed CR or confirmed PR) to the date of first documented disease progression or death due to any cause. If a patient not had an event, duration was censored at the date of last adequate tumor assessment before the start of a new anticancer therapy, if any.
DOR was analyzed using the Kaplan-Meier method as defined in the statistical analysis plan.
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Timepoint [4]
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Up to 1.3 years
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Secondary outcome [5]
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Overall Survival (OS)
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Assessment method [5]
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OS is defined as the time from the date of randomization to the date of death due to any cause.
The requirement for survival follow-up period was removed following the discontinuation of one of the investigational drugs (capmatinib) in all subjects in the combination arm and the implementation of Protocol Amendment 03.
OS was analyzed using the Kaplan-Meier method as defined in the statistical analysis plan.
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Timepoint [5]
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Up to 2.1 years
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Secondary outcome [6]
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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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Assessment method [6]
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Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.
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Timepoint [6]
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From first dose of study treatment to 30 days after last dose, up to 2.1 years
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Secondary outcome [7]
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Maximum Observed Plasma Concentration (Cmax) of Capmatinib
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Assessment method [7]
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Pharmacokinetic (PK) parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
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Timepoint [7]
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pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 2 Day 1. The duration of one cycle was 21 days.
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Secondary outcome [8]
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Time to Reach Maximum Plasma Concentration (Tmax) of Capmatinib
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Assessment method [8]
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PK parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
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Timepoint [8]
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pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 2 Day 1. The duration of one cycle was 21 days.
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Secondary outcome [9]
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Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Capmatinib
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Assessment method [9]
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PK parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
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Timepoint [9]
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pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 2 Day 1. The duration of one cycle was 21 days.
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Secondary outcome [10]
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Trough Serum Concentration (Ctrough) of Pembrolizumab
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Assessment method [10]
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PK parameters were calculated based on pembrolizumab serum concentrations by using non-compartmental methods. Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
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Timepoint [10]
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pre-dose on Cycle 2 Day 1, Cycle 3 Day 1, Cycle 6 Day 1 and Cycle 12 Day 1. The duration of one cycle was 21 days.
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Secondary outcome [11]
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Number of Participants With Anti-pembrolizumab Antibodies
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Assessment method [11]
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Immunogenicity (IG) was evaluated in serum samples. The assay to quantify and assess the IG was a validated homogeneous enzyme-linked immunosorbent assay (ELISA).
* ADA-negative at baseline: ADA-negative sample at baseline
* ADA-positive at baseline: ADA-positive sample at baseline
* ADA-negative post-baseline: patient with ADA-negative sample at baseline and at least 1 post baseline determinant sample, all of which are ADA-negative samples
* ADA-positive post-baseline: patient with at least 1 ADA-positive sample post baseline
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Timepoint [11]
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Baseline (pre-dose), up to 8 months
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Eligibility
Key inclusion criteria
* Histologically confirmed and documented locally advanced stage III (not candidates for surgical resection or definitive chemo-radiation) or stage IV (metastatic) NSCLC (per AJCC/IASLC v.8) for treatment in the first-line setting
* Histologically or cytologically confirmed diagnosis of NSCLC that is both EGFR wild type status and ALK- negative rearrangement statu
* Have an archival tumor sample or newly obtained tumor biopsy with high PD-L1 expression (TPS = 50%)
* ECOG performance status score = 1
* Have at least 1 measurable lesion by RECIST 1.1
* Have adequate organ function
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Prior treatment with a MET inhibitor or HGF-targeting therapy
* Prior immunotherapy (e.g. anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways)
* Have untreated symptomatic central nervous system (CNS) metastases
* Clinically significant, uncontrolled heart diseases
* Prior palliative radiotherapy for bone lesions = 2 weeks prior to starting study treatment
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
22/01/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
7/02/2023
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Sample size
Target
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Accrual to date
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Final
76
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Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
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Recruitment hospital [1]
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Novartis Investigative Site - Wollongong
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Recruitment hospital [2]
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Novartis Investigative Site - North Adelaide
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Recruitment hospital [3]
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Novartis Investigative Site - Shepparton
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Recruitment postcode(s) [1]
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2500 - Wollongong
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Recruitment postcode(s) [2]
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5006 - North Adelaide
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Recruitment postcode(s) [3]
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3630 - Shepparton
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Recruitment outside Australia
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Belgium
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State/province [1]
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Yvoir
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Canada
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Quebec
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Czechia
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State/province [3]
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Ostrava Vitkovice
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France
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State/province [4]
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Lille
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France
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State/province [5]
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Strasbourg Cedex
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France
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State/province [6]
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Toulouse
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Germany
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Berlin
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Germany
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Koeln
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Greece
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Athens
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Greece
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State/province [10]
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Thessaloniki
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Hong Kong
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State/province [11]
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Shatin New Territories
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India
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Maharashtra
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India
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West Bengal
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India
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Delhi
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Italy
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AN
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Italy
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PN
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Japan
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Aichi
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Japan
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Kanagawa
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Malaysia
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Sarawak
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Malaysia
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Kuala Lumpur
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Netherlands
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Amersfoort
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Netherlands
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Breda
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Netherlands
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Zwolle
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Spain
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Catalunya
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Spain
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Comunidad Valenciana
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Spain
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Barcelona
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Spain
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Madrid
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Taiwan
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Changhua
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Taiwan
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Taichung
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Thailand
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State/province [30]
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Bangkok
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Novartis Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose was to evaluate the efficacy and safety of the combination of capmatinib with pembrolizumab compared to pembrolizumab alone as first-line treatment for subjects with locally advanced or metastatic NSCLC who have PD-L1 expression = 50% and have no EGFR mutation or ALK rearrangement. Capmatinib has demonstrated immunomodulatory activities when combined with an anti-PD1 antibody in preclinical tumor models irrespective of MET dysregulation. The combination of capmatinib with checkpoint inhibitors has been established to be tolerable and could provide additional clinical benefit to the subjects.
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Trial website
https://clinicaltrials.gov/study/NCT04139317
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Contact person for public queries
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Address
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Fax
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
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What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/17/NCT04139317/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/17/NCT04139317/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04139317