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Safety and Efficacy of Capmatinib (INC280) Plus Pembrolizumab vs Pembrolizumab Alone in NSCLC With PD-L1≥ 50%

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04139317
Recruitment Status : Active, not recruiting
First Posted : October 25, 2019
Last Update Posted : April 26, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer (NSCLC) Drug: Capmatinib Biological: Pembrolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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%
Actual Study Start Date : January 22, 2020
Actual Primary Completion Date : January 14, 2022
Estimated Study Completion Date : February 16, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Combination arm
Capmatinib 400 mg twice a day Pembrolizumab 200mg every 3 weeks
Drug: Capmatinib
Oral tablet
Other Name: INC280

Biological: Pembrolizumab
IV infusion
Other Names:
  • Keytruda®
  • MK-3475

Active Comparator: monotherapy
Pembrolizumab 200mg every 3 weeks
Biological: Pembrolizumab
IV infusion
Other Names:
  • Keytruda®
  • MK-3475




Primary Outcome Measures :
  1. Progression-free survival (PFS) based on local investigator assessment as per RECIST 1.1 [ Time Frame: 18 months ]
    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


Secondary Outcome Measures :
  1. Objective response rate (ORR) based on local investigator assessment as per RECIST 1.1 [ Time Frame: 18 months ]
    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

  2. Disease control rate (DCR) based on local investigator assessment as per RECIST 1.1 [ Time Frame: 18 months ]
    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

  3. Time-to-response (TTR) based on local investigator assessment as per RECIST 1.1 [ Time Frame: 18 months ]
    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

  4. Duration of response (DOR) based on local investigator assessment as per RECIST 1.1 [ Time Frame: 18 months ]
    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

  5. Overall survival (OS) [ Time Frame: 18 months ]
    Overall survival is defined as the time from date of randomization to date of death due to any cause

  6. Antidrug antibodies (ADA) of pembrolizumab [ Time Frame: 13 months ]
    Concentration/presence of ADA to be measured

  7. AUC of capmatinib derived from plasma capmatinib concentration [ Time Frame: 13 months ]
    AUC of capmatinib is defined as area under the plasma concentration-time curve determined using non-compartmental methods.

  8. Ctrough of pembrolizumab derived from serum pembrolizumab concentration [ Time Frame: 13 months ]
    Ctrough of pembrolizumab is defined as the measured serum concentration at the end of a dosing interval at steady state

  9. Cmax of capmatinib derived from plasma capmatinib concentration [ Time Frame: 13 months ]
    Cmax of capmatinib is defined as the maximum observed plasma concentration after single dose administration

  10. Tmax of capmatinib derived from plasma capmatinib concentration [ Time Frame: 13 months ]
    Tmax of capmatinib is defined as the time to reach maximum plasma concentration after single dose administration

  11. Incidence of adverse events [ Time Frame: 19 months ]
    Incidence of adverse events is defined as number of participants with adverse events (AEs), serious adverse events (SAEs) and AEs leading to dose interruption, dose reduction and dose discontinuation.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04139317


Locations
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Australia, New South Wales
Novartis Investigative Site
Wollongong, New South Wales, Australia, 2500
Australia, South Australia
Novartis Investigative Site
North Adelaide, South Australia, Australia, 5006
Australia, Victoria
Novartis Investigative Site
Shepparton, Victoria, Australia, 3630
Belgium
Novartis Investigative Site
Bruxelles, Belgium, 1000
Novartis Investigative Site
Liege, Belgium, 4000
Novartis Investigative Site
Yvoir, Belgium, 5530
Canada
Novartis Investigative Site
Quebec, Canada, GIV 4G5
Czechia
Novartis Investigative Site
Ostrava Vitkovice, Czechia, 703 84
France
Novartis Investigative Site
Lille, France, 59000
Novartis Investigative Site
Strasbourg Cedex, France, 67091
Novartis Investigative Site
Toulouse, France, 31400
Germany
Novartis Investigative Site
Berlin, Germany, 14165
Novartis Investigative Site
Koeln, Germany, 50937
Greece
Novartis Investigative Site
Athens, Greece, 11526
Novartis Investigative Site
Thessaloniki, Greece, 57001
Hong Kong
Novartis Investigative Site
Shatin, New Territories, Hong Kong
India
Novartis Investigative Site
Mumbai, Maharashtra, India, 401107
Novartis Investigative Site
Kolkata, West Bengal, India, 700160
Novartis Investigative Site
Delhi, India, 110 085
Italy
Novartis Investigative Site
Ancona, AN, Italy, 60126
Novartis Investigative Site
Aviano, PN, Italy, 33081
Japan
Novartis Investigative Site
Nagoya, Aichi, Japan, 466 8560
Novartis Investigative Site
Yokohama-city, Kanagawa, Japan, 236 0051
Malaysia
Novartis Investigative Site
Kuching, Sarawak, Malaysia, 93586
Novartis Investigative Site
Kuala Lumpur, Malaysia, 59100
Netherlands
Novartis Investigative Site
Amersfoort, Netherlands, 3813 TZ
Novartis Investigative Site
Breda, Netherlands, 4819 EV
Novartis Investigative Site
Zwolle, Netherlands, 8025 AB
Spain
Novartis Investigative Site
Badalona, Catalunya, Spain, 08916
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Valencia, Comunidad Valenciana, Spain, 46010
Novartis Investigative Site
Barcelona, Spain, 08041
Novartis Investigative Site
Madrid, Spain, 28040
Taiwan
Novartis Investigative Site
Changhua, Taiwan, 50006
Novartis Investigative Site
Taichung, Taiwan, 40705
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10330
Novartis Investigative Site
Bangkok, Thailand, 10400
Novartis Investigative Site
Bangkok, Thailand, 10700
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04139317    
Other Study ID Numbers: CINC280I12201
First Posted: October 25, 2019    Key Record Dates
Last Update Posted: April 26, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
capmatinib, pembrolizumab, NSCLC, PD-L1, EGFR, ALK, MET, squamous, non-squamous
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents