AzTrials
AzTrials

Carcinoma, Non-Small-Cell LungPhase 2NCT02414139

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 2 study testing Capmatinib in people with Carcinoma, Non-Small-Cell Lung, run by Novartis Pharmaceuticals at 95 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
Capmatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
373 participants
Where
95 sitesin 20 countries
Study dates
11 Jun 2015to 16 May 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • EGFR wt status (for exon 19 deletions and exon 21 L858R substitution mutations)
  • and ALK rearrangement-negative
  • 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).
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  • 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

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

95 sites in 20 countries.

95 sites in 20 countries

Germany14 sites

  • Novartis Investigative Site

    Berlin, 13125

  • Novartis Investigative Site

    Cologne, 50937

  • Novartis Investigative Site

    Frankfurt, 60590

  • Novartis Investigative Site

    Göttingen, 37075

  • Novartis Investigative Site

    Halle, 06120

  • Novartis Investigative Site

    Hamburg, 20251

  • Novartis Investigative Site

    Hanover, 30625

  • Novartis Investigative Site

    Heidelberg, Baden-Wurttemberg, 69126

  • Novartis Investigative Site

    Homburg, 66421

  • Novartis Investigative Site

    München, 81925

  • Novartis Investigative Site

    Nuremberg, 90419

  • Novartis Investigative Site

    Ravensburg, 88214

  • Novartis Investigative Site

    Tübingen, 72076

  • Novartis Investigative Site

    Ulm, 89081

Other trials in Germany

United States13 sites

  • Lehigh Valley Health Network SC

    Allentown, Pennsylvania, 18103

  • VA Ann Arbor Health System VA Ann Arbor Health System

    Ann Arbor, Michigan, 48105

  • Massachusetts General Hospital MGH Cancer Center

    Boston, Massachusetts, 02114

  • Andrew and Patel Associates

    Camp Hill, Pennsylvania, 17011

  • University of Iowa Hospitals and Clinics SC-3

    Iowa City, Iowa, 52242

  • Pacific Shores Medical Group SC

    Long Beach, California, 90813

  • University Of California Los Angeles Dept of Onc

    Los Angeles, California, 90095

  • University of California Irvine Medical Center Chao Family Chao Family Comp Cancer Center

    Orange, California, 92868

  • Oregon Health and Science University SC

    Portland, Oregon, 97239

  • Mayo Clinic Rochester .

    Rochester, Minnesota, 55905

  • University of Utah / Huntsman Cancer Institute Oncology

    Salt Lake City, Utah, 84103

  • Mays Cancer Ctr Uthsa Mdacc SC-5

    San Antonio, Texas, 78229

  • H Lee Moffitt Cancer Center and Research Institute .

    Tampa, Florida, 33612

Other trials in United States

Italy13 sites

  • Novartis Investigative Site

    Bologna, BO, 40138

  • Novartis Investigative Site

    Brescia, BS, 25123

  • Novartis Investigative Site

    Catania, CT, 95124

  • Novartis Investigative Site

    Catanzaro, CZ, 88100

  • Novartis Investigative Site

    Florence, FI, 50134

  • Novartis Investigative Site

    Meldola, FC, 47014

  • Novartis Investigative Site

    Milan, MI, 20141

  • Novartis Investigative Site

    Milan, MI, 20162

  • Novartis Investigative Site

    Modena, MO, 41124

  • Novartis Investigative Site

    Monza, MB, 20900

  • Novartis Investigative Site

    Naples, 80131

  • Novartis Investigative Site

    Roma, RM, 00155

  • Novartis Investigative Site

    Verona, VR, 37126

Other trials in Italy

France10 sites

  • Novartis Investigative Site

    Clermont-Ferrand, 63011

  • Novartis Investigative Site

    Dijon, Cote D Or, 21034

  • Novartis Investigative Site

    La Tronche, 38700

  • Novartis Investigative Site

    Lille, 59000

  • Novartis Investigative Site

    Marseille, Bouches Du Rhone, 13915

  • Novartis Investigative Site

    Marseille, 13273

  • Novartis Investigative Site

    Paris, 75970

  • Novartis Investigative Site

    Pierre-Bénite, 69495

  • Novartis Investigative Site

    Rennes, 35043

  • Novartis Investigative Site

    Strasbourg, 67091

Other trials in France

Japan10 sites

  • Novartis Investigative Site

    Akashi, Hyōgo, 673-8558

  • Novartis Investigative Site

    Chuo Ku, Tokyo, 104 0045

  • Novartis Investigative Site

    Fukuoka, Fukuoka, 811-1395

  • Novartis Investigative Site

    Koto Ku, Tokyo, 135 8550

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 464 8681

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 466 8560

  • Novartis Investigative Site

    Okayama, Okayama-ken, 700-8558

  • Novartis Investigative Site

    Ōsaka-sayama, Osaka, 589 8511

  • Novartis Investigative Site

    Sendai, Miyagi, 980 0873

  • Novartis Investigative Site

    Ube, Yamaguchi, 755-0241

Other trials in Japan

Spain7 sites

  • Novartis Investigative Site

    A Coruña, Galicia, 15006

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    Barcelona, Catalonia, 08036

  • Novartis Investigative Site

    Madrid, 28034

  • Novartis Investigative Site

    Madrid, 28041

  • Novartis Investigative Site

    Oviedo, Principality of Asturias, 33011

  • Novartis Investigative Site

    Seville, Andalusia, 41009

Other trials in Spain

Netherlands4 sites

  • Novartis Investigative Site

    Amsterdam, 1066 CX

  • Novartis Investigative Site

    Groningen, 9713 GZ

  • Novartis Investigative Site

    Maastricht, 6229 HX

  • Novartis Investigative Site

    Rotterdam, 3015 GD

Other trials in Netherlands

Argentina3 sites

  • Novartis Investigative Site

    Buenos Aires, Buenos Aires F.D., C1431FWO

  • Novartis Investigative Site

    CABA, Buenos Aires, C1426ANZ

  • Novartis Investigative Site

    La Rioja, 5300

Other trials in Argentina

Russia3 sites

  • Novartis Investigative Site

    Moscow, 109028

  • Novartis Investigative Site

    Saint Petersburg, 192148

  • Novartis Investigative Site

    Tambov, 392000

Other trials in Russia

South Korea3 sites

  • Novartis Investigative Site

    Bundang Gu, Gyeonggi-do, 13620

  • Novartis Investigative Site

    Gyeonggi-do, Korea, 10408

  • Novartis Investigative Site

    Seoul, 03080

Other trials in South Korea

Taiwan3 sites

  • Novartis Investigative Site

    Kaohsiung City, 82445

  • Novartis Investigative Site

    Taipei, 10002

  • Novartis Investigative Site

    Taoyuan, 33305

Other trials in Taiwan

Israel2 sites

  • Novartis Investigative Site

    Ramat Gan, 52621

  • Novartis Investigative Site

    Tel Aviv, 6423906

Other trials in Israel

Singapore2 sites

  • Novartis Investigative Site

    Singapore, 119228

  • Novartis Investigative Site

    Singapore, 168583

Other trials in Singapore

United Kingdom2 sites

  • Novartis Investigative Site

    Birmingham, B9 5SS

  • Novartis Investigative Site

    London, W6 8RF

Other trials in United Kingdom

Austria1 site

  • Novartis Investigative Site

    Vienna, 1210

Other trials in Austria

Belgium1 site

  • Novartis Investigative Site

    Leuven, 3000

Other trials in Belgium

Lebanon1 site

  • Novartis Investigative Site

    El Achrafiyé, 166830

Other trials in Lebanon

Mexico1 site

  • Novartis Investigative Site

    Mexico City, Mexico City, 14080

Other trials in Mexico

Norway1 site

  • Novartis Investigative Site

    Oslo, NO 0424

Other trials in Norway

Sweden1 site

  • Novartis Investigative Site

    Stockholm, SE-171 76

Other trials in Sweden

About this study

Official title: 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.

Read the 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.

Being tested
Capmatinib
Keywords
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
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis, Lung Neoplasms, Adenocarcinoma of Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CapmatinibDrug

    Also called INC280

    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.

Study groups in NCT02414139
Study groupRoleWhat they receive
Cohort 1a: Pre-treated patients with MET GCN ≥ 10 (2/3L)ExperimentalPre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)
Receives: Drug: Capmatinib
Cohort 1b:Pre-treated patients with MET GCN ≥ 6 and < 10 (2/3L)ExperimentalPre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)
Receives: Drug: Capmatinib
Cohort 2: Pre-treated patients with MET GCN ≥ 4 and < 6 (2/3L)ExperimentalPre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)
Receives: Drug: Capmatinib
Cohort 3: Pre-treated patients with MET GCN < 4 (2/3L)ExperimentalPre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)
Receives: Drug: Capmatinib
Cohort 4: Pre-treated patients with MET mutation regardless of MET GCN (2/3L)ExperimentalPre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)
Receives: Drug: Capmatinib
Cohort 5a: Treatment-naïve patients with MET GCN ≥10 (1L)ExperimentalTreatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)
Receives: Drug: Capmatinib
Cohort 5b: Treatment-naïve patients with MET mutation regardless of MET GCN (1L)ExperimentalTreatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)
Receives: Drug: Capmatinib
Cohort 6.1 (expansion of Cohort 1a): Pre-treated patients MET GCN ≥ 10 without MET mutation (2L)ExperimentalPre-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)
Receives: Drug: Capmatinib
Cohort 6.2 (expansion of Cohort 4): Pre-treated patients with MET mutation (2L)ExperimentalPre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)
Receives: Drug: Capmatinib
Cohort 7 (expansion of Cohort 5b): Treatment-naïve with MET mutation regardless of MET GCN (1L)ExperimentalTreatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
Receives: Drug: Capmatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to approximately 5 years

Secondary outcomes (17)

  1. 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.

    Measured: Up to approximately 5 years

  2. 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.

    Measured: Up to approximately 5 years

  3. 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.

    Measured: Up to approximately 5 years

  4. 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.

    Measured: Up to approximately 5 years

  5. 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.

    Measured: Up to approximately 5 years

  6. 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.

    Measured: Up to approximately 5 years

  7. 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

    Measured: Up to approximately 5 years

  8. 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.

    Measured: Up to approximately 6 years

  9. 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.

    Measured: 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

  10. 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

    Measured: 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

  11. 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

    Measured: 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

  12. 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

    Measured: Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days

  13. 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

    Measured: Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days

  14. 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

    Measured: 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

  15. 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

    Measured: 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

  16. 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

    Measured: 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

  17. 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

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Apr 2015 (estimated)
  2. Study start11 Jun 2015
  3. Primary completion12 Apr 2023
  4. Study completion16 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
373 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02414139
Sponsor's protocol ID
CINC280A2201
Other IDs
2014-003850-15, 2014
Status last verified
Feb 2024
First submitted
31 Mar 2015
Last updated
20 Mar 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • Wolf J, Hochmair M, Han JY, Reguart N, Souquet PJ, Smit EF, Orlov SV, Vansteenkiste J, Nishio M, de Jonge M, Akerley W, Garon EB, Groen HJM, Tan DSW, Seto T, Frampton GM, Robeva A, Carbini M, Le Mouhaer S, Yovine A, Boran A, Bossen C, Yang Y, Ji L, Fairchild L, Heist RS. Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial. Lancet Oncol. 2024 Oct;25(10):1357-1370. doi: 10.1016/S1470-2045(24)00441-8.

    PubMed 39362249

  • Wolf J, Garon EB, Groen HJM, Tan DSW, Gilloteau I, Le Mouhaer S, Hampe M, Cai C, Chassot-Agostinho A, Reynolds M, Sherif B, Heist RS. Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study. Eur J Cancer. 2023 Apr;183:98-108. doi: 10.1016/j.ejca.2022.10.030. Epub 2022 Dec 10.

    PubMed 36822130

  • 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.

    PubMed 32877583

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Capmatinib in people with Carcinoma, Non-Small-Cell Lung, run by Novartis Pharmaceuticals at 95 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 95 sites in Germany, United States, Italy, France, Japan and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment (time frame: Up to approximately 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02414139, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2024.

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