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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04139317




Registration number
NCT04139317
Ethics application status
Date submitted
14/10/2019
Date registered
25/10/2019
Date last updated
9/09/2020

Titles & IDs
Public title
Safety and Efficacy of Capmatinib (INC280) Plus Pembrolizumab vs Pembrolizumab Alone in NSCLC With PD-L1= 50%
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%
Secondary ID [1] 0 0
CINC280I12201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer (NSCLC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Capmatinib
Other interventions - Pembrolizumab

Experimental: Combination arm - Capmatinib 400 mg twice a day Pembrolizumab 200mg every 3 weeks

Active Comparator: monotherapy - Pembrolizumab 200mg every 3 weeks


Treatment: Drugs: Capmatinib
Oral tablet

Other interventions: Pembrolizumab
IV infusion

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) based on local investigator assessment as per RECIST 1.1 - Progression free survival is defined as the time from randomization to the date of the first documented radiological progression using RECIST 1.1(Response evaluation criteria in solid tumor) or death due to any cause
Timepoint [1] 0 0
24 months
Secondary outcome [1] 0 0
Objective response rate (ORR) based on local investigator assessment as per RECIST 1.1 - ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Disease control rate (DCR) based on local investigator assessment as per RECIST 1.1 - Disease control rate is defined as the proportion of patients with complete response (CR) or partial response (PR) or subjects with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Time-to-response (TTR) based on local investigator assessment as per RECIST 1.1 - Time to response (TTR) is defined as duration of time between the date of randomization and the date of first documented response of either CR or PR, according to RECIST 1.1 criteria
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Duration of response (DOR) based on local investigator assessment as per RECIST 1.1 - Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death, according to RECIST 1.1 criteria
Timepoint [4] 0 0
24 months
Secondary outcome [5] 0 0
Overall survival (OS) - Overall survival is defined as the time from date of randomization to date of death due to any cause
Timepoint [5] 0 0
38 months
Secondary outcome [6] 0 0
Antidrug antibodies (ADA) of pembrolizumab - Concentration/presence of ADA to be measured
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
AUC of Capmatinib derived from plasma capmatinib concentration
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Ctrough of Pembrolizumab derived from serum pembrolizumab concentration
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Cmax of Capmatinib derived from plasma capmatinib concentration
Timepoint [9] 0 0
24 months
Secondary outcome [10] 0 0
Tmax of Capmatinib derived from plasma capmatinib concentration
Timepoint [10] 0 0
24 months

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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Wollongong
Recruitment hospital [2] 0 0
Novartis Investigative Site - Shepparton
Recruitment postcode(s) [1] 0 0
2500 - Wollongong
Recruitment postcode(s) [2] 0 0
3630 - Shepparton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Tennessee
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Belgium
State/province [3] 0 0
Liege
Country [4] 0 0
Belgium
State/province [4] 0 0
Yvoir
Country [5] 0 0
Czechia
State/province [5] 0 0
Ostrava Vitkovice
Country [6] 0 0
France
State/province [6] 0 0
LILLE Cédex
Country [7] 0 0
France
State/province [7] 0 0
Strasbourg Cedex
Country [8] 0 0
France
State/province [8] 0 0
Toulouse Cedex 9
Country [9] 0 0
Germany
State/province [9] 0 0
Berlin
Country [10] 0 0
Germany
State/province [10] 0 0
Heidelberg
Country [11] 0 0
Germany
State/province [11] 0 0
Koeln
Country [12] 0 0
Germany
State/province [12] 0 0
Ulm
Country [13] 0 0
Hong Kong
State/province [13] 0 0
Shatin, New Territories
Country [14] 0 0
India
State/province [14] 0 0
West Bengal
Country [15] 0 0
India
State/province [15] 0 0
Delhi
Country [16] 0 0
Italy
State/province [16] 0 0
AN
Country [17] 0 0
Japan
State/province [17] 0 0
Aichi
Country [18] 0 0
Japan
State/province [18] 0 0
Kanagawa
Country [19] 0 0
Malaysia
State/province [19] 0 0
Sarawak
Country [20] 0 0
Malaysia
State/province [20] 0 0
Kuala Lumpur
Country [21] 0 0
Spain
State/province [21] 0 0
Catalunya
Country [22] 0 0
Spain
State/province [22] 0 0
Cataluña
Country [23] 0 0
Spain
State/province [23] 0 0
Comunidad Valenciana
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Taiwan
State/province [25] 0 0
Changhua
Country [26] 0 0
Thailand
State/province [26] 0 0
Bangkok

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose is 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.
Trial website
https://clinicaltrials.gov/show/NCT04139317
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04139317