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Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (Geometry Mono-1)

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: NCT02414139
Recruitment Status : Active, not recruiting
First Posted : April 10, 2015
Last Update Posted : April 13, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
A phase II study to evaluate antitumor activity of oral cMET inhibitor INC280 in adult patients with EGFR wild-type, advanced non-small cell lung cancer (NSCLC) as measured by overall response rate (ORR). The study will also evaluate safety and pharmacokinetics of INC280.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: INC280 (capmatinib) Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 373 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type (wt), Advanced Non-small Cell Lung Cancer (NSCLC)(Geometry Mono-1)
Actual Study Start Date : June 11, 2015
Estimated Primary Completion Date : April 12, 2023
Estimated Study Completion Date : May 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Capmatinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: cMET GCN ≥ 6
Pre-treated patients with cMET GCN ≥ 6 treated with INC280 at 400mg BID as second or third line
 Drug: INC280 (capmatinib)
Experimental: cMET GCN ≥ 4 and < 6
Pre-treated patients with cMET GCN ≥ 4 and < 6 treated with INC280 at 400 mg BID as second or third line
 Drug: INC280 (capmatinib)
Experimental: cMET GCN < 4
Pre-treated patients with cMET GCN < 4 treated with INC280 at 400mg BID as second or third line
 Drug: INC280 (capmatinib)
Experimental: cMET mutations
Pre-treated patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID as second or third line
 Drug: INC280 (capmatinib)
Experimental: cMET dysregulation - treatment-naïve
Treatment-naïve patients with cMET dysregulation treated with INC280 at 400mg BID
 Drug: INC280 (capmatinib)
Experimental: cMET dysregulation - second line
Pre-treated patients with cMET deregulation treated with INC280 at 400 mg BID as second line
 Drug: INC280 (capmatinib)
Experimental: cMET mutations treatment-naïve
Treatment-naïve patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID
 Drug: INC280 (capmatinib)


Outcome Measures
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Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: at least 18 weeks ]
    Proportion of patients with a best overall response defined as complete response (CR) or partial response (PR) by Blinded Independent Review Committee (BIRC) assessment per RECIST 1.1


Secondary Outcome Measures :
  1. Duration of Response (DOR) - Key Secondary [ Time Frame: at least 18 weeks ]
    Calculated as the time from the date of the first documented CR or PR by Blinded Independent Review Committee (BIRC) per RECIST 1.1 to the first documented progression or death due to any cause for patients with PR or CR.

  2. Overall Response Rate (ORR) [ Time Frame: at least 18 weeks ]
    ORR (complete response (CR)+ partial response (PR)) per RECIST 1.1 by investigator assessment

  3. Duration of Response (DOR) [ Time Frame: at least 18 weeks ]
    DOR per RECIST 1.1 by investigator assessment

  4. Time to Response (TTR) [ Time Frame: at least 18 weeks ]
    TTR per RECIST 1.1 both by BIRC and investigator assessment

  5. Disease Control Rate (DCR) [ Time Frame: at least 18 weeks ]
    DCR per RECIST 1.1 both by BIRC and investigator assessment

  6. Progression-free Survival (PFS) [ Time Frame: at least 18 weeks ]
    PFS per RECIST 1.1 both by BIRC and investigator assessment

  7. Overall Survival (OS) [ Time Frame: at least 18 weeks ]
    OS, defined as time from first dose of INC280 to death due to any cause

  8. Number of patients with incidence of adverse events and serious adverse events, change in vital signs, laboratory results (hematology, blood chemistry, and urinalysis) and ECG. [ Time Frame: at least 18 weeks ]
    Safety of INC280

  9. Cmax, Cmin and plasma concentration-time profiles of INC280 [ Time Frame: 6 weeks ]
    Pharmacokinetics of INC280 and metabolite CMN288


Eligibility Criteria
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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:

  • Stage IIIB or IV NSCLC (any histology) at the time of study entry

  • Histologically or cytologically confirmed diagnosis of NSCLC that is:

    1. EGFR wt as per patient standard of care by a validated test
    2. AND ALK-negative rearrangement as part of the patient standard of care by a validated test

    3. AND (by central assessment) either:

      • Cohort 1: Pre-treated patients with cMET GCN ≥ 6 or
      • Cohort 2: Pre-treated patients with cMET GCN ≥4 and < 6, or
      • Cohort 3: Pre-treated patients with cMET GCN < 4, or
      • Cohort 4: Pre-treated patients with cMET mutations regardless of cMET GCN, or
      • Cohort 5: Treatment-naïve patients with cMET dysregulation, or
      • Cohort 6: Pre-treated patients with either cMET GCN ≥ 10 without cMET mutations or cMET mutations regardless of cMET GCN, or
      • Cohort 7: Treatment-naïve patients with cMET mutations regardless of cMET GCN
  • To be eligible for Cohorts 1-4, patients must have failed one or two prior lines of systemic therapy for advanced/metastatic disease
  • To be eligible for Cohort 6, patients must have failed one prior line of systemic therapy for advanced/metastatic disease
  • To be eligible for Cohort 5 and Cohort 7, patients must not have received any systemic therapy for advanced/metastatic disease
  • At least one measurable lesion as defined by RECIST 1.1
  • Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter the study.
  • Patients must have adequate organ function
  • ECOG performance status (PS) of 0 or 1 Details and other protocol-defined inclusion criteria may apply

Exclusion Criteria:

  • Prior treatment with crizotinib, or any other cMET or HGF inhibitor
  • Patients with characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations
  • Patients with characterized ALK-positive rearrangement
  • Clinically significant, uncontrolled heart diseases.

  • Patients receiving treatment with medications that cannot be discontinued at least 1 week prior to first INC280 treatment and for the duration of the study:

    • Strong inducers of CYP3A4
  • Impairment of GI function or GI disease that may significantly alter the absorption of INC280
  • Patients receiving treatment with any enzyme-inducing anticonvulsant
  • Applicable to Cohorts 1-4 and Cohort 6 only: Previous anti-cancer and investigational agents within 4 weeks or ≤ 5 x half-life of the agent (whichever is longer) before first dose
  • Pregnant or nursing women
  • Women of child-bearing potential, unless they are using highly effective methods of contraception
  • Sexually active males unless they use a condom during intercourse
  • Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis

Other protocol-defined exclusion criteria may apply

Contacts and Locations
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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): NCT02414139


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02414139    
Other Study ID Numbers: CINC280A2201
2014-003850-15 ( EudraCT Number )
First Posted: April 10, 2015    Key Record Dates
Last Update Posted: April 13, 2023
Last Verified: April 2023
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 ):
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
Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
 Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms