Carcinoma, Non-Small-Cell LungPhase 3GeoMETry-IIINCT04427072
Study of Capmatinib Efficacy in Comparison With Docetaxel in Previously Treated Participants With Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation
A Phase 3 study testing Capmatinib and Docetaxel in people with Carcinoma, Non-Small-Cell Lung, run by Novartis Pharmaceuticals at 43 sites in 18 countries.
Trial summary
The purpose of the study was to learn whether the study drug (capmatinib) helps to control lung cancer better compared to a single agent chemotherapy (docetaxel) and whether it is safe when given to patients suffering from a particular type of lung cancer. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Capmatinib and Docetaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 43 sitesin 18 countries
- Study dates
- 25 Sep 2020to 6 Nov 2023
- Phase
- Phase 3
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Stage IIIB/IIIC (not amenable to surgery, radiation or multi modality therapy) or IV NSCLC (according to Version 8 of the American Joint Committee on Cancer (AJCC) Staging Manual) at the time of study entry.
- Histologically or cytologically confirmed diagnosis of NSCLC that was:
- EGFR wt. Assessed as part of participant's standard of care by a validated test for EGFR mutations as per local guidelines. The EGFR wt status (for EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations.
- AND ALK rearrangement negative. Assessed as part of participant's standard of care by a validated test.
- AND had METΔex14 mutation as determined by Novartis-designated central laboratory or by locally performed, tissue-based test, validated according to local regulation, from a Clinical Laboratory Improvement Amendments (CLIA)-certified US laboratory or an accredited local laboratory outside of the US. The positive METΔex14 mutation result as determined per local test must have been documented in the participant's source documents and in the CRF prior to entering main screening.
- Mandatory provision of a formalin-fixed, paraffin embedded tumor tissue sample (archival tumor block or slides, or a newly obtained tumor sample) with quality and quantity sufficient to allow assessment of METΔex14 mutation status (as defined in the study [laboratory manual]). This pertained to all participants, including those who had a METΔex14 mutation result from a local test. Tumor samples must have contained at least 10% tumor content.
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- 6. Participants must have progressed on one or two prior lines of systemic therapy for advanced/metastatic disease (stage IIIB/IIIC [not candidates for surgery, radiation or multi modality therapy] or IV NSCLC) and must have been docetaxel naïve and candidates for single agent chemotherapy (docetaxel). Treatment failure was defined as documented disease progression or intolerance to treatment, however, participants must have progressed on or after the last therapy before study entry.
- At least one measurable lesion as defined by RECIST 1.1
- Adequate organ function
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Life expectancy of at least 3 months.
Who cannot join
- Prior treatment with any MET inhibitor or HGF-targeting therapy.
- Participants with symptomatic central nervous system (CNS) metastases who were neurologically unstable or had required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
- Participants with known druggable molecular alterations (such as ROS1 and RET rearrangement, BRAF mutation, KRAS mutation, NTRK fusion, etc.) which might have been a candidate for alternative targeted therapies.
- 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).
- Substance abuse, active infection or other severe, acute, or chronic medical or psychotic conditions or laboratory abnormalities that in the opinion of the investigator may have increased the risk associated with study participation.
Trial locations and contacts
43 sites in 18 countries.
43 sites in 18 countries
Germany6 sites
Novartis Investigative Site
Berlin, 13125
Novartis Investigative Site
Berlin, 14165
Novartis Investigative Site
Cologne, 50937
Novartis Investigative Site
Gauting, Bavaria, 82131
Novartis Investigative Site
Oldenburg, 26121
Novartis Investigative Site
Regensburg, Bavaria, 93053
Russia4 sites
Novartis Investigative Site
Nizhny Novgorod, 603081
Novartis Investigative Site
Omsk, 644013
Novartis Investigative Site
Pushkin Saint Petersburg, 196603
Novartis Investigative Site
Saint Petersburg, 197022
Spain4 sites
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Málaga, Andalusia, 29010
Novartis Investigative Site
Oviedo, Principality of Asturias, 33011
Novartis Investigative Site
Valencia, 46026
Brazil3 sites
Novartis Investigative Site
Barretos, São Paulo, 14784 400
Novartis Investigative Site
São Paulo, São Paulo, 01246 000
Novartis Investigative Site
São Paulo, São Paulo, 04014-002
Bulgaria3 sites
Novartis Investigative Site
Pleven, 5800
Novartis Investigative Site
Sofia, 1303
Novartis Investigative Site
Sofia, 1407
France3 sites
Novartis Investigative Site
Caen, 14021
Novartis Investigative Site
Paris, 75231
Novartis Investigative Site
Pierre-Bénite, 69495
India3 sites
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110076
Novartis Investigative Site
Pune, Maharashtra, 411013
Novartis Investigative Site
Vellore, Tamil Nadu, 632 004
Malaysia3 sites
Novartis Investigative Site
Kuala Lumpur, Kuala Lumpur, 50586
Novartis Investigative Site
Kuantan, Pahang, 25100
Novartis Investigative Site
Pulau Pinang, 10990
Hungary2 sites
Novartis Investigative Site
Budapest, 1121
Novartis Investigative Site
Törökbálint, Pest County, 2045
Italy2 sites
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Roma, RM, 00128
Portugal2 sites
Novartis Investigative Site
Lisbon, 1769 001
Novartis Investigative Site
Matosinhos Municipality, 4454 513
Thailand2 sites
Novartis Investigative Site
Bangkok, 10700
Novartis Investigative Site
Songkhla, Hat Yai, 90110
South Africa1 site
Novartis Investigative Site
Port Elizabeth, Western Cape, 6045
About this study
Official title: A Phase III, Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib Versus SoC Docetaxel Chemotherapy in Previously Treated Patients With EGFR wt, ALK Negative, Locally Advanced or Metastatic (Stage IIIB/IIIC or IV) NSCLC Harboring MET Exon 14 Skipping Mutation (METΔex14).
The purpose of the study was to learn whether the study drug (capmatinib) helps to control lung cancer better compared to a single agent chemotherapy (docetaxel) and whether it is safe when given to patients suffering from a particular type of lung cancer. This type of cancer is called non-small cell lung cancer (NSCLC) with certain specific genetic alterations (called mutations) of a gene called MET, within a specific part of the gene called exon 14.
Read the detailed description
Twenty-two patients with advanced or metastatic lung cancer, with these specific mutations in the MET gene but without changes in their epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genes, were enrolled in this study. Participants were randomly assigned to get either capmatinib or docetaxel in a 2 to 1 ratio. The randomization was stratified by prior lines of systemic therapy received for advanced/metastatic disease (one line vs. two lines).
During treatment, visits were scheduled every 21 days.
For all participants, the respective treatment (either with capmatinib or docetaxel) could be continued beyond initial disease progression as per RECIST 1.1 (as assessed by the investigator and confirmed by BIRC) if, in the judgment of the investigator, there was evidence of clinical benefit, and the participant wished to continue on the study treatment. After treatment discontinuation, all participants were followed for safety evaluations during the safety follow-up period, and the participant's status was collected every 12 weeks as part of the survival follow-up.
Participants randomized to docetaxel treatment were eligible to cross over to receive capmatinib treatment after BIRC-confirmed, RECIST 1.1-defined progressive disease and after meeting the eligibility criteria prior to crossover. This was the extension treatment phase.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Capmatinib, Docetaxel
- Keywords
- Non small cell lung cancer, Non small cell lung carcinoma, NSCLC, INC280, capmatinib, MET mutation, MET exon14, MET exon14 skipping, MET exon14 deletion, METex14, METex14del, MET∆ex14, EGFRwt, Epidermal growth factor receptor wild type, ALK negative, docetaxel
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapmatinibDrug
Also called INC280
400 mg, capmatinib tablets, administered orally twice daily
DocetaxelDrug
Docetaxel 75 mg/m^2 by intravenous infusion every 21 days
| Study group | Role | What they receive |
|---|---|---|
| Capmatinib | Experimental | 400 mg, capmatinib tablets, administered orally twice daily Receives: Drug: Capmatinib |
| Docetaxel | Active comparator | Docetaxel 75 mg/m^2 solution administered by intravenous infusion on Day 1 of every 21-day cycle Receives: Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) Per Blinded Independent Review Committee (BIRC) Using RECIST v1.1
Progression-free survival was defined as the time from the date of randomization to the date of the first documented progressive disease (PD) as assessed by BIRC according to RECIST 1.1, or death due to any cause. PD=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. PFS was censored at the date of the last adequate tumor assessment, if no PFS event was observed prior to the analysis cut-off date.
Measured: From randomization to the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 21 months
Secondary outcomes (20)
Overall Response (ORR) Per RECIST 1.1 by BIRC
Percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR), assessed by BIRC according to RECIST 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as 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 21 months
Overall Response Rate (ORR) Per RECIST 1.1 by Investigator
Percentage of participants with confirmed BOR of CR or PR, assessed by local review according to RECIST 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as 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 21 months
Time to Response (TTR) Per RECIST 1.1 by BIRC
Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by BIRC according to RECIST 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as 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: From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months
Time to Response (TTR) Per RECIST 1.1 by Investigator
Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by local review according to RECIST 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as 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: From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months
Duration of Response (DOR) Per RECIST 1.1 by BIRC
Duration of response was defined as the time from the date of first documented response (CR or PR) to the first documented progression by BIRC per RECIST 1.1 or death due to any cause. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as 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: From first documented response to first documented progression or death due to any cause, whichever came first, assessed up to approximately 21 months
Duration of Response (DOR) Per RECIST 1.1 by Investigator
Duration of response was defined as the time from the date of first documented response (CR or PR) to the first documented progression by local review per RECIST 1.1 or death due to any cause. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as 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: From first documented response to first documented progression or death due to any cause, whichever came first, assessed up to approximately 21 months
Disease Control Rate (DCR) Per RECIST 1.1 by BIRC
Disease control rate was defined as the percentage of participants with a best overall response (BOR) of confirmed CR, PR and stable disease (SD) assessed by BIRC according to RECIST 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as 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 21 months
Disease Control Rate (DCR) Per RECIST 1.1 by Investigator
Disease control rate was defined as the percentage of participants with a best overall response (BOR) of confirmed CR, PR and stable disease (SD) assessed by local review according to RECIST 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as 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 21 months
Progression-free Survival (PFS) Per Investigator Using RECIST v1.1
Progression-free survival was defined as the time from the date of randomization to the date of the first documented progressive disease (PD) as assessed by local review according to RECIST 1.1, or death due to any cause. PD=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.
Measured: From randomization to the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 21 months
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death due to any cause.
Measured: From randomization to death due to any cause, assessed up to approximately 36 months
Overall Intracranial Response Rate (OIRR)
Percentage of participants with confirmed best overall intracranial response (BOIR) of CR or partial response (PR), as assessed by BIRC review per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Criteria for CR: Disappearance of all central nervous system (CNS) target and non-target lesions sustained for at least 4 weeks, with no new lesions, and no use of corticosteroids. PR: ≥30% decrease in the sublaterodorsal tegmental nucleus (SLD) of CNS target lesions or no new lesions or and stable to decreased corticosteroid dose.
Measured: Up to approximately 21 months
Duration of Intracranial Response (DOIR)
Time from date of first documented intracranial response (CR or PR) to first documented intracranial progression per RANO-BM assessed by BIRC or date of death due to underlying cause of cancer.
Measured: From date of first documented intracranial response (CR or PR) to first documented intracranial progression, assessed up to approximately 21 months
Time to Intracranial Response (TTIR)
Time from date of randomization to first documented intracranial response of either CR or PR, per RANO-BM criteria and assessed by BIRC, which must be subsequently confirmed.
Measured: From date of randomization to first documented intracranial response of either CR or PR, assessed up to approximately 21 months
Intracranial Disease Control Rate (IDCR)
Percentage of participants with a BOR of confirmed CR, PR and stable disease (SD) (or non-CR/non-PD) per RANO-BM, assessed by BIRC. Criteria for CR: Disappearance of all central nervous system (CNS) target and non-target lesions sustained for at least 4 weeks, with no new lesions, and no use of corticosteroids. PR: ≥30% decrease in the sublaterodorsal tegmental nucleus (SLD) of CNS target lesions or no new lesions or and stable to decreased corticosteroid dose.
Measured: Up to approximately 21 months
Plasma Capmatinib Concentration
Plasma concentrations of capmatinib. Blood samples were collected at indicated time points for pharmacokinetic analysis.
Measured: Cycle (C) 1 Day (D) 15 pre-dose, 1 and 4 hours post-dose, C3 D1 pre-dose. Each cycle duration was 21 days.
Change From Baseline in Score as Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. The questionnaire is composed of both multi-item scales and single-item measures based on the participants experience over the past week. These include five domains (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact) and a global health status/HRQoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. CFB = change from baseline.
Measured: Baseline, Cycle (C) 3, Day (D) 1 and then every 6 weeks up to approximately 21 months, end of treatment. Each cycle duration was 21 days.
Change From Baseline in Score as Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13)
EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire. The assessments here included coughing, hemoptysis, dyspnea, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, and pain in other parts and were based on their presence over the previous week. All but the pain domain were scored on a 4 point Likert scale ranging from "not at all" to "very much." Pain was scored based on its presence, yes or no. Scores were averaged and transformed to 0 to 100. A higher score indicated a higher presence of symptoms. CFB = change from baseline.
Measured: Baseline, Cycle (C) 3, Day (D) 1 and then every 6 weeks up to approximately 21 months, end of treatment. Each cycle duration was 21 days.
Change From Baseline in Score as Per European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Questionnaire
EQ-5D-5L is a standardized measure to assess the overall health-related quality of life in patients. The EQ-5D-5L consists of 2 parts- the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: from 1 (no problems) to 5 (extreme problems). The EQ VAS is a self-perceived health score assessed using a visual analogue scale that ranges from 0 (the worst imaginable health) to 100 (the best imaginable health), with higher scores indicating higher health utility. CFB = change from baseline.
Measured: Baseline, Cycle (C) 3, Day (D) 1 and then every 6 weeks up to approximately 21 months, end of treatment. Each cycle duration was 21 days.
Time to Symptom Deterioration for Chest Pain, Cough and Dyspnea Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13)
EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire. The assessments here included chest pain, cough, and dyspnea and were based on their presence over the previous week. All but the pain domain were scored on a 4 point Likert scale ranging from "not at all" to "very much." Pain was scored based on its presence, yes or no. Scores were averaged and transformed to 0 to 100. A higher score indicated a higher presence of symptoms. Time to symptom deterioration for chest pain, cough and dyspnea was assessed. Deterioration was assessed by the investigator.
Measured: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12, 18 weeks post treatment. Each cycle duration was 21 days.
Time to Deterioration for Global Health Status /QoL Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. The questionnaire is composed of both multi-item scales and single-item measures based on the participants experience over the past week. These include five domains (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/HRQoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Time to deterioration in QoL from EORTC-QLQ-C30 was assessed. Deterioration was assessed by the investigator.
Measured: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12, 18 weeks post treatment. Each cycle duration was 21 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start25 Sep 2020
- Primary completion15 Feb 2023
- Study completion6 Nov 2023
Why it stopped: Company decision not related to any safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants randomized to docetaxel treatment will be eligible to crossover to receive capmatinib treatment after blinded independent review committee (BIRC)-confirmed, RECIST 1.1- defined disease progression.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04427072
- Sponsor's protocol ID
- CINC280A2301
- Other IDs
- 2020-001578-31
- Acronym
- GeoMETry-III
- Status last verified
- May 2025
- First submitted
- 9 Jun 2020
- Last updated
- 16 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- 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
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib Versus SoC Docetaxel Chemotherapy in Previously Treated Patients With EGFR wt, ALK Negative, Locally Advanced or Metastatic (Stage IIIB/IIIC or IV) NSCLC Harboring MET Exon 14 Skipping Mutation (METΔex14).
- ClinicalTrials.gov ID
- NCT04427072
- Acronym / sponsor ID
- GeoMETry-III / CINC280A2301
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- Non small cell lung cancer, Non small cell lung carcinoma, NSCLC, INC280, capmatinib, MET mutation, MET exon14, MET exon14 skipping
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company decision not related to any safety concerns.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 25 Sep 2020 (actual)
- Primary completion
- 15 Feb 2023 (actual)
- Study completion
- 6 Nov 2023 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Posted 30 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study was to learn whether the study drug (capmatinib) helps to control lung cancer better compared to a single agent chemotherapy (docetaxel) and whether it is safe when given to patients suffering from a particular type of lung cancer. This type of cancer is called non-small cell lung cancer (NSCLC) with certain specific genetic alterations (called mutations) of a gene called MET, within a specific part of the gene called exon 14.
Detailed description
Twenty-two patients with advanced or metastatic lung cancer, with these specific mutations in the MET gene but without changes in their epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genes, were enrolled in this study. Participants were randomly assigned to get either capmatinib or docetaxel in a 2 to 1 ratio. The randomization was stratified by prior lines of systemic therapy received for advanced/metastatic disease (one line vs. two lines).
During treatment, visits were scheduled every 21 days.
For all participants, the respective treatment (either with capmatinib or docetaxel) could be continued beyond initial disease progression as per RECIST 1.1 (as assessed by the investigator and confirmed by BIRC) if, in the judgment of the investigator, there was evidence of clinical benefit, and the participant wished to continue on the study treatment. After treatment discontinuation, all participants were followed for safety evaluations during the safety follow-up period, and the participant's status was collected every 12 weeks as part of the survival follow-up.
Participants randomized to docetaxel treatment were eligible to cross over to receive capmatinib treatment after BIRC-confirmed, RECIST 1.1-defined progressive disease and after meeting the eligibility criteria prior to crossover. This was the extension treatment phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants randomized to docetaxel treatment will be eligible to crossover to receive capmatinib treatment after blinded independent review committee (BIRC)-confirmed, RECIST 1.1- defined disease progression.
| Arm | Type | Receives |
|---|---|---|
| Capmatinib | Experimental | Drug: Capmatinib400 mg, capmatinib tablets, administered orally twice daily |
| Docetaxel | Active comparator | Drug: DocetaxelDocetaxel 75 mg/m^2 solution administered by intravenous infusion on Day 1 of every 21-day cycle |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Stage IIIB/IIIC (not amenable to surgery, radiation or multi modality therapy) or IV NSCLC (according to Version 8 of the American Joint Committee on Cancer (AJCC) Staging Manual) at the time of study entry.
- Histologically or cytologically confirmed diagnosis of NSCLC that was:
- Mandatory provision of a formalin-fixed, paraffin embedded tumor tissue sample (archival tumor block or slides, or a newly obtained tumor sample) with quality and quantity sufficient to allow assessment of METΔex14 mutation status (as defined in the study [laboratory manual]). This pertained to all participants, including those who had a METΔex14 mutation result from a local test. Tumor samples must have contained at least 10% tumor content.
- 6. Participants must have progressed on one or two prior lines of systemic therapy for advanced/metastatic disease (stage IIIB/IIIC [not candidates for surgery, radiation or multi modality therapy] or IV NSCLC) and must have been docetaxel naïve and candidates for single agent chemotherapy (docetaxel). Treatment failure was defined as documented disease progression or intolerance to treatment, however, participants must have progressed on or after the last therapy before study entry.
- At least one measurable lesion as defined by RECIST 1.1
Key exclusion criteria (5 listed)
- Prior treatment with any MET inhibitor or HGF-targeting therapy.
- Participants with symptomatic central nervous system (CNS) metastases who were neurologically unstable or had required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
- Participants with known druggable molecular alterations (such as ROS1 and RET rearrangement, BRAF mutation, KRAS mutation, NTRK fusion, etc.) which might have been a candidate for alternative targeted therapies.
- 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).
- Substance abuse, active infection or other severe, acute, or chronic medical or psychotic conditions or laboratory abnormalities that in the opinion of the investigator may have increased the risk associated with study participation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapmatinibAlso: INC280400 mg, capmatinib tablets, administered orally twice daily | Drug | Capmatinib |
| DocetaxelDocetaxel 75 mg/m^2 by intravenous infusion every 21 days | Drug | Docetaxel |
Primary outcome
Progression-free Survival (PFS) Per Blinded Independent Review Committee (BIRC) Using RECIST v1.1
Time frame: From randomization to the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 21 months
Progression-free survival was defined as the time from the date of randomization to the date of the first documented progressive disease (PD) as assessed by BIRC according to RECIST 1.1, or death due to any cause. PD=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. PFS was censored at the date of the last adequate tumor assessment, if no PFS event was observed prior to the analysis cut-off date.
20 secondary outcomes
Overall Response (ORR) Per RECIST 1.1 by BIRC
Time frame: Up to approximately 21 months
Overall Response Rate (ORR) Per RECIST 1.1 by Investigator
Time frame: Up to approximately 21 months
Time to Response (TTR) Per RECIST 1.1 by BIRC
Time frame: From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months
Time to Response (TTR) Per RECIST 1.1 by Investigator
Time frame: From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months
Duration of Response (DOR) Per RECIST 1.1 by BIRC
Time frame: From first documented response to first documented progression or death due to any cause, whichever came first, assessed up to approximately 21 months
Duration of Response (DOR) Per RECIST 1.1 by Investigator
Time frame: From first documented response to first documented progression or death due to any cause, whichever came first, assessed up to approximately 21 months
Disease Control Rate (DCR) Per RECIST 1.1 by BIRC
Time frame: Up to approximately 21 months
Disease Control Rate (DCR) Per RECIST 1.1 by Investigator
Time frame: Up to approximately 21 months
Progression-free Survival (PFS) Per Investigator Using RECIST v1.1
Time frame: From randomization to the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 21 months
Overall Survival (OS)
Time frame: From randomization to death due to any cause, assessed up to approximately 36 months
Overall Intracranial Response Rate (OIRR)
Time frame: Up to approximately 21 months
Duration of Intracranial Response (DOIR)
Time frame: From date of first documented intracranial response (CR or PR) to first documented intracranial progression, assessed up to approximately 21 months
Time to Intracranial Response (TTIR)
Time frame: From date of randomization to first documented intracranial response of either CR or PR, assessed up to approximately 21 months
Intracranial Disease Control Rate (IDCR)
Time frame: Up to approximately 21 months
Plasma Capmatinib Concentration
Time frame: Cycle (C) 1 Day (D) 15 pre-dose, 1 and 4 hours post-dose, C3 D1 pre-dose. Each cycle duration was 21 days.
Change From Baseline in Score as Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
Time frame: Baseline, Cycle (C) 3, Day (D) 1 and then every 6 weeks up to approximately 21 months, end of treatment. Each cycle duration was 21 days.
Change From Baseline in Score as Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13)
Time frame: Baseline, Cycle (C) 3, Day (D) 1 and then every 6 weeks up to approximately 21 months, end of treatment. Each cycle duration was 21 days.
Change From Baseline in Score as Per European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Questionnaire
Time frame: Baseline, Cycle (C) 3, Day (D) 1 and then every 6 weeks up to approximately 21 months, end of treatment. Each cycle duration was 21 days.
Time to Symptom Deterioration for Chest Pain, Cough and Dyspnea Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13)
Time frame: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12, 18 weeks post treatment. Each cycle duration was 21 days.
Time to Deterioration for Global Health Status /QoL Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
Time frame: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12, 18 weeks post treatment. Each cycle duration was 21 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
43 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Capmatinib and Docetaxel in people with Carcinoma, Non-Small-Cell Lung, run by Novartis Pharmaceuticals at 43 sites in 18 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 5 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: stopped early, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in Germany, Russia, Spain, Brazil, Bulgaria and 13 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 30 Jan 2025). 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?
Progression-free Survival (PFS) Per Blinded Independent Review Committee (BIRC) Using RECIST v1.1 (time frame: From randomization to the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 21 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 May 2025.