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

A Phase II, Multicenter Study of Oral MET Inhibitor INC280 in Adult Patients With EGFR Wild-type (wt), Advanced Non-small Cell Lung Cancer (NSCLC) (Geometry Mono-1)

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Capmatinib

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.

• Study Type: Interventional
• Enrollment (Actual): 373
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • La Rioja, Argentina, 5300
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1426ANZ
      • Novartis Investigative Site
  • Caba
    • Buenos Aires, Caba, Argentina, C1431FWO
      • Novartis Investigative Site
• Austria
  • Wien, Austria, 1210
    • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• France
  • Clermont-Ferrand, France, 63011
    • Novartis Investigative Site
  • La Tronche, France, 38700
    • Novartis Investigative Site
  • Lille, France, 59000
    • Novartis Investigative Site
  • Marseille, France, 13273
    • Novartis Investigative Site
  • Paris, France, 75970
    • Novartis Investigative Site
  • Pierre Benite, France, 69495
    • Novartis Investigative Site
  • Rennes, France, 35043
    • Novartis Investigative Site
  • Strasbourg Cedex, France, 67091
    • Novartis Investigative Site
  • Bouches Du Rhone
    • Marseille cedex 20, Bouches Du Rhone, France, 13915
      • Novartis Investigative Site
  • Cote D Or
    • Dijon, Cote D Or, France, 21034
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13125
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Halle (Saale), Germany, 06120
    • Novartis Investigative Site
  • Hamburg, Germany, 20251
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Koeln, Germany, 50937
    • Novartis Investigative Site
  • Muenchen, Germany, 81925
    • Novartis Investigative Site
  • Nuernberg, Germany, 90419
    • Novartis Investigative Site
  • Ravensburg, Germany, 88214
    • Novartis Investigative Site
  • Tuebingen, Germany, 72076
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69126
      • Novartis Investigative Site
• Israel
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95124
      • Novartis Investigative Site
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • Novartis Investigative Site
  • FC
    • Meldola, FC, Italy, 47014
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50134
      • Novartis Investigative Site
  • MB
    • Monza, MB, Italy, 20900
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
    • Milano, MI, Italy, 20141
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41124
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00155
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 466 8560
      • Novartis Investigative Site
    • Nagoya, Aichi, Japan, 464 8681
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 811-1395
      • Novartis Investigative Site
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Novartis Investigative Site
  • Miyagi
    • Sendai city, Miyagi, Japan, 980 0873
      • Novartis Investigative Site
  • Okayama
    • Okayama-city, Okayama, Japan, 700-8558
      • Novartis Investigative Site
  • Osaka
    • Osaka Sayama, Osaka, Japan, 589 8511
      • Novartis Investigative Site
  • Tokyo
    • Chuo ku, Tokyo, Japan, 104 0045
      • Novartis Investigative Site
    • Koto ku, Tokyo, Japan, 135 8550
      • Novartis Investigative Site
  • Yamaguchi
    • Ube-city, Yamaguchi, Japan, 755-0241
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Gyeonggi Do
    • Bundang Gu, Gyeonggi Do, Korea, Republic of, 13620
      • Novartis Investigative Site
  • Korea
    • Gyeonggi do, Korea, Korea, Republic of, 10408
      • Novartis Investigative Site
• Lebanon
  • Ashrafieh, Lebanon, 166830
    • Novartis Investigative Site
• Mexico
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 14080
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Novartis Investigative Site
  • Groningen, Netherlands, 9713 GZ
    • Novartis Investigative Site
  • Maastricht, Netherlands, 6229 HX
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3015 GD
    • Novartis Investigative Site
• Norway
  • Oslo, Norway, NO 0424
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 109028
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 192148
    • Novartis Investigative Site
  • Tambov, Russian Federation, 392000
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119228
    • Novartis Investigative Site
  • Singapore, Singapore, 168583
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
• Sweden
  • Stockholm, Sweden, SE-171 76
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 82445
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taoyuan, Taiwan, 33305
    • Novartis Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Novartis Investigative Site
  • London, United Kingdom, W6 8RF
    • Novartis Investigative Site
• United States
  • California
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group SC
    • Los Angeles, California, United States, 90095
      • University Of California Los Angeles Dept of Onc
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center Chao Family Chao Family Comp Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H Lee Moffitt Cancer Center and Research Institute .
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics SC-3
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital MGH Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • VA Ann Arbor Health System VA Ann Arbor Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester .
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University SC
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network SC
    • Camp Hill, Pennsylvania, United States, 17011
      • Andrew and Patel Associates
  • Texas
    • San Antonio, Texas, United States, 78229
      • Mays Cancer Ctr Uthsa Mdacc SC-5
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • University of Utah / Huntsman Cancer Institute Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: Capmatinib; 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.; Other Names: INC280
Experimental: 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)	Drug: Capmatinib; 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.; Other Names: INC280
Experimental: 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)	Drug: Capmatinib; 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.; Other Names: INC280
Experimental: 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)	Drug: Capmatinib; 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.; Other Names: INC280
Experimental: 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)	Drug: Capmatinib; 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.; Other Names: INC280
Experimental: 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)	Drug: Capmatinib; 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.; Other Names: INC280
Experimental: 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)	Drug: Capmatinib; 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.; Other Names: INC280
Experimental: 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)	Drug: Capmatinib; 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.; Other Names: INC280
Experimental: 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)	Drug: Capmatinib; 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.; Other Names: INC280
Experimental: 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)	Drug: Capmatinib; 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.; Other Names: INC280

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 5 years
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.	Up to approximately 5 years
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.	Up to approximately 5 years
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.	Up to approximately 5 years
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.	Up to approximately 5 years
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.	Up to approximately 5 years
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	Up to approximately 5 years
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.	Up to approximately 6 years
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.	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
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	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
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	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
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	Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
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	Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
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	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
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	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
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	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
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	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Wolf J, Seto T, Han JY, Reguart N, Garon EB, Groen HJM, Tan DSW, Hida T, de Jonge M, Orlov SV, Smit EF, Souquet PJ, Vansteenkiste J, Hochmair M, Felip E, Nishio M, Thomas M, Ohashi K, Toyozawa R, Overbeck TR, de Marinis F, Kim TM, Laack E, Robeva A, Le Mouhaer S, Waldron-Lynch M, Sankaran B, Balbin OA, Cui X, Giovannini M, Akimov M, Heist RS; GEOMETRY mono-1 Investigators. Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer. N Engl J Med. 2020 Sep 3;383(10):944-957. doi: 10.1056/NEJMoa2002787.

Helpful Links

• For interim results on this study, please click the link below to the NovartisClinicalTrial.com website

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2015
• Primary Completion (Actual): April 12, 2023
• Study Completion (Actual): May 16, 2023

Study Registration Dates

• First Submitted: March 31, 2015
• First Submitted That Met QC Criteria: April 7, 2015
• First Posted (Estimated): April 10, 2015

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; lung cancer; Non Small Cell Lung Cancer; Non-small cell lung cancer; INC280; MET amplification; MET mutation; lung adenocarcinoma; Non Small Cell Lung; 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; Non small cell lung carcinoma; MET exon 14 deletion; METex14del; MET exon 14 skipping; MET exon 14 mutation; MET inhibitor; MET dysregulation; MET activation; MET signaling; MET pathway; met; cMET; Geometry mono-1; Geometry
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma
• Other Study ID Numbers: CINC280A2201; 2014-003850-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No