Study of Capmatinib in Chinese Adult Patients With Advanced Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation (GeoMETry-C)

A Phase II, Multicenter, Two-cohort Study of Oral MET Inhibitor Capmatinib in Chinese Adult Patients With EGFR Wild-type (wt), ALK Rearrangement Negative, MET Exon 14 Skipping Mutations, Advanced Non-small Cell Lung Cancer (NSCLC) Who Are Treatment Naive or Failed One or Two Prior Lines of Systemic Therapy

The purpose of the study was to learn whether the study treatment (capmatinib), which already shows efficacy and safety in non-Chinese patients, could help Chinese patients with controlling their lung cancer in a safe way. Participants had a type of lung cancer called non-small cell lung lancer (NSCLC), with a specific alteration in a part of their DNA (called mutation) of the MET gene, within a specific part of this gene called exon 14.

Participants who had advanced (or metastatic) non-small cell lung cancer with specific mutations in the MET gene but without mutations in the EGFR or ALK genes, who were aged 18 years or older were enrolled in this study.

The study drug, capmatinib (also known as INC280), is an oral drug that is called a 'targeted' medicine, which means it targets particular processes that may not be working properly in cancer cells (called dysregulation). The dysregulation of the MET signaling in cancer cells of patients with NSCLC is believed to make the cancer worse. Capmatinib has been shown to selectively block the effects of the MET gene and therefore may help in keeping the disease under control, stopping cancer cells from growing.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Capmatinib

Detailed Description

This was an open-label, multicenter two-cohort phase II study. Chinese adult participants with EGFR wild-type (wt) (EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations), anaplastic lymphoma kinase (ALK) rearrangement negative, advanced (stage IIIB, IIIC or IV) NSCLC disease harboring MET exon 14-skipping (METΔex14) mutations as determined by a Novartis central molecular laboratory were treated in this study. Cohort 1 included treatment naive participants and Cohort 2 participants who failed one or two prior lines of therapy in the advanced stage (stage IIIB, IIIC or IV). Each participant received 400 mg capmatinib tablet twice daily (BID) until either the disease worsened or there were other reasons to discontinue the drug.

After treatment discontinuation, participants were followed for safety up to 30 days after the last dose of study drug. In addition to the 30-day safety follow-up, participants who discontinued treatment without documented progressive disease (PD) continued efficacy assessments and patient-reported outcomes (PROs) collection during the post-treatment follow-up until documented progression.

After the post-treatment follow-up phase, the participant's survival status was collected as part of the survival follow-up phase.

The primary endpoint was the overall response rate (ORR) by cohort as per the blinded independent review committee (BIRC) review. ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST 1.1.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100142
    • Novartis Investigative Site
  • Shanghai, China, 200030
    • Novartis Investigative Site
  • Tianjin, China, 300052
    • Novartis Investigative Site
  • Fujian
    • Xiamen, Fujian, China, 361001
      • Novartis Investigative Site
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • Novartis Investigative Site
    • Guangzhou, Guangdong, China, 510080
      • Novartis Investigative Site
    • Guangzhou, Guangdong, China, 510515
      • Novartis Investigative Site
    • Guangzhou, Guangdong, China, 524000
      • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Novartis Investigative Site
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430024
      • Novartis Investigative Site
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • Novartis Investigative Site
  • Shandong
    • Jinan, Shandong, China, 250117
      • Novartis Investigative Site
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200030
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Yunnan
    • Kunming, Yunnan, China, 650106
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Chinese adult ≥ 18 years old at the time of informed consent
• Histologically confirmed stage IIIB, IIIC or IV NSCLC at the time of study entry, not amenable to curative surgery or radiation or multi-modality therapy (according to staging definition in CSCO guidelines for primary lung cancer, 2019).

• Histologically or cytologically confirmed diagnosis of NSCLC that is:

  1. EGFR wt: The EGFR wt status assessed as part of standard of care (EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations)
  2. AND ALK rearrangement negative: assessed as part of standard of care by validated test
  3. AND either:

Cohort 1: Treatment naive participants with MET mutations, or Cohort 2: Pre-treated participants with MET mutations

• Cohort 1: participants must not have received any systemic therapy for advanced/metastatic disease (stage IIIB, IIIC or IV NSCLC). Neo-adjuvant and adjuvant systemic therapies will not count as one prior line of treatment if relapse occurred > 12 months from the end of the neo-adjuvant or adjuvant systemic therapy.
• Cohort 2: participants must have failed one or two prior lines of systemic therapy for advanced/metastatic disease (stage IIIB, IIIC or IV NSCLC).
• At least one measurable lesion according to RECIST v1.1.
• Adequate organ function
• ECOG performance status (PS) ≤1

Key Exclusion Criteria:

• Prior treatment with any MET inhibitor or HGF-targeting therapy.
• Known druggable molecular alterations (such as ROS1 translocation or BRAF mutation, etc.) which might be a candidate for alternative targeted therapies as applicable per local regulations and treatment guidelines.
• Participants with 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.
• Presence or history of interstitial lung disease or interstitial pneumonitis, including, clinically significant radiation pneumonitis affecting activities of daily living or requiring therapeutic intervention.
• Substance abuse, active infection (including active hepatitis B and C, participants whose disease is controlled under antiviral therapy are eligible, and human immunodeficiency virus (HIV) history positive) or other severe, acute, or chronic medical or psychotic conditions or laboratory abnormalities that in the opinion of the investigator may increase the risk associated with study participation, or that may interfere with the interpretation of study results.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Treatment Naive participants	Drug: Capmatinib; 400 mg of capmatinib tablets, administered orally twice daily; Other Names: INC280
Experimental: Cohort 2; Participants received one or two prior lines of treatment	Drug: Capmatinib; 400 mg of capmatinib tablets, administered orally twice daily; Other Names: INC280

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) Per RECIST v1.1 by BIRC Assessment	Tumor response was assessed by a blinded independent review committee (BIRC) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR). For RECIST v1.1, 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. The primary efficacy endpoint ORR was estimated and the exact 95% confidence interval (CI) was provided by cohort.	Up to approximately 125 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration Of Response (DOR) Per RECIST v1.1 by BIRC Assessment	DOR only applies to patients whose best overall response is complete response (CR) or partial response (PR) based on BIRC assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response of CR or PR to the date of first documented progression or death due to any cause. If a patient did not have an event, DOR was censored as defined in the statistical analysis plan. DOR was estimated using the Kaplan-Meier method.	Up to approximately 189 weeks (median 33.6 weeks)
Overall Response Rate (ORR) Per RECIST v1.1 by Investigator Assessment	Tumor response was assessed by the investigator based on RECIST v1.1. ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR). For RECIST v1.1, 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.	Up to approximately 189 weeks (median 33.6 weeks)
Duration Of Response (DOR) Per RECIST v1.1 by Investigator Assessment	DOR only applies to patients whose best overall response is complete response (CR) or partial response (PR) based on investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response of CR or PR to the date of first documented progression or death due to any cause. If a patient did not have an event, DOR was censored as defined in the statistical analysis plan. DOR was estimated using the Kaplan-Meier method.	Up to approximately 189 weeks (median 33.6 weeks)
Time To Response (TTR) Per RECIST v1.1 by BIRC and Investigator Assessment	TTR is defined as the time from the start date of study drug to the first documented response of either CR or PR, which must be subsequently confirmed. If a patient did not have an event, TTR was censored as defined in the statistical analysis plan. Tumor response was assessed by BIRC and by the investigator based on RECIST v1.1. TTR was estimated using the Kaplan-Meier method.	Up to approximately 189 weeks (median 33.6 weeks)
Disease Control Rate (DCR) Per RECIST v1.1 by BIRC and Investigator Assessment	DCR is the percentage of patients with a best overall response of CR, PR or stable disease (SD), based on BIRC review and local investigator assessment per RECIST v1.1.	Up to approximately 189 weeks (median 33.6 weeks)
Progression-Free Survival (PFS) Per RECIST v1.1 by BIRC and Investigator Assessment	PFS is defined as the time from the start date of study drug to the date of the first radiologically documented progressive disease (PD) or death due to any cause. If a patient did not have an event, PFS was censored as defined in the statistical analysis plan. Tumor response was assessed by BIRC and by the investigator based on RECIST v1.1. PFS was estimated using the Kaplan-Meier method.	Up to approximately 193 weeks (median 37.6 weeks)
Overall Survival (OS)	OS is defined as the time from the start date of study drug to the date of death due to any cause. If a patient did not have an event, OS was censored as defined in the statistical analysis plan. OS was estimated using the Kaplan-Meier method.	Up to approximately 193 weeks (median 37.6 weeks)
Overall Intracranial Response Rate (OIRR) Per RANO-BM Criteria by BIRC Assessment	OIRR was calculated based on response assessments in the brain for participants having measurable or non-measurable brain metastases at baseline. OIRR is defined as the percentage of participants with a confirmed best overall intracranial response of CR or PR from the start of treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started) per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria as assessed by BIRC review.	Up to approximately 189 weeks (median 33.6 weeks)
Intracranial Disease Control Rate (IDCR) Per RANO-BM Criteria by BIRC Assessment	IDCR is defined as the percentage of participants with a confirmed best overall intracranial response of CR or PR or SD (or non-CR/non-PD) per RANO-BM criteria as assessed by BIRC review.	Up to approximately 189 weeks (median 33.6 weeks)
Time To Intracranial Response (TTIR) Per RANO-BM Criteria by BIRC Assessment	TTIR is defined as the time from the start date of study drug to the date of the first documented intracranial response of either CR or PR per RANO-BM criteria as assessed by the BIRC review, which must be subsequently confirmed. If a patient did not have an event, TTIR was censored as defined in the statistical analysis plan. TTIR was estimated using the Kaplan-Meier method.	Up to approximately 189 weeks (median 33.6 weeks)
Duration Of Intracranial Response (DOIR) Per RANO-BM Criteria by BIRC Assessment	DOIR only applies to participants whose confirmed best overall intracranial response is CR or PR per RANO-BM criteria as assessed by the BIRC review. DOIR is defined as the time from the date of first documented intracranial response of either CR or PR to the date of the first documented intracranial progression per RANO-BM criteria as assessed by BIRC review or date of death due to any cause. If a patient did not have an event, DOIR was censored as defined in the statistical analysis plan. DOIR was estimated using the Kaplan-Meier method.	Up to approximately 189 weeks (median 33.6 weeks)
ORR Per RECIST v1.1 by BIRC and Investigator Assessment for Patients by MET Mutation Status in ctDNA	At Cycle 1 Day 1 (C1D1, pre-dose), blood samples were collected to investigate the association between Mesenchymal Epithelial Transition (MET) mutation status in baseline circulating tumor DNA (ctDNA) and capmatinib efficacy. These blood samples were tested for MET exon 14 (METex14) skipping mutations and classified as mutant or non-mutant. ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR). Tumor response was assessed by BIRC and by the investigator based on RECIST v1.1.	Baseline, up to approximately 189 weeks (median 33.6 weeks)
DOR Per RECIST v1.1 by BIRC Assessment for Patients by MET Mutation Status in ctDNA	At Cycle 1 Day 1 (C1D1, pre-dose), blood samples were collected to investigate the association between MET mutation status in baseline ctDNA and capmatinib efficacy. These blood samples were tested for METex14 skipping mutations and classified as mutant or non-mutant. DOR only applies to patients whose best overall response is CR or PR based on BIRC assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response of CR or PR to the date of first documented progression or death due to any cause. If a patient did not have an event, DOR was censored as defined in the statistical analysis plan. DOR was estimated using the Kaplan-Meier method.	Baseline, up to approximately 189 weeks (median 33.6 weeks)
DOR Per RECIST v1.1 by Investigator Assessment for Patients by MET Mutation Status in ctDNA	At Cycle 1 Day 1 (C1D1, pre-dose), blood samples were collected to investigate the association between MET mutation status in baseline ctDNA and capmatinib efficacy. These blood samples were tested for METex14 skipping mutations and classified as mutant or non-mutant. DOR only applies to patients whose best overall response is CR or PR based on investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response of CR or PR to the date of first documented progression or death due to any cause. If a patient did not have an event, DOR was censored as defined in the statistical analysis plan. DOR was estimated using the Kaplan-Meier method.	Baseline, up to approximately 189 weeks (median 33.6 weeks)
PFS Per RECIST v1.1 by BIRC and Investigator Assessment for Patients by MET Mutation Status in ctDNA	At Cycle 1 Day 1 (C1D1, pre-dose), blood samples were collected to investigate the association between MET mutation status in baseline ctDNA and capmatinib efficacy. These blood samples were tested for METex14 skipping mutations and classified as mutant or non-mutant. PFS is defined as the time from the start date of study drug to the date of the first radiologically documented PD or death due to any cause. If a patient did not have an event, PFS was censored as defined in the statistical analysis plan. Tumor response was assessed by BIRC and by the investigator based on RECIST v1.1. PFS was estimated using the Kaplan-Meier method.	Baseline, up to approximately 189 weeks (median 33.6 weeks)
Capmatinib Plasma Concentrations at Steady-state	Plasma capmatinib concentrations at steady state were quantified using a validated liquid chromatography tandem-mass spectrometry assay. Concentrations below the lower limit of quantification were treated as zero in the calculations. Pre-dose concentrations correspond to Ctrough, defined as the lowest plasma drug concentration observed immediately before the next dose.	Cycle 2 Day 1 (C2D1): Pre-dose, 1 hour (±0.5 hours) and 4 hours (±1 hour). Cycle 3 Day 1 (C3D1): Pre-dose. Each cycle duration is 21 days.
Number of Participants With AEs and SAEs During the On-treatment Period	Number of participants with AEs (any adverse events regardless of seriousness) and serious adverse events (SAEs), including changes in physical exams, electrocardiograms and laboratory results qualifying and reported as AEs. AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For CTCAE v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. The on-treatment period is defined from the day of first administration of study drug up to 30 days after the date of the last actual administration of study drug.	Up to approximately 193 weeks (median 37.6 weeks)
Change From Baseline in EORTC QLQ-C30: Global Health Status/Quality of Life (QoL) Scale	The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items and is composed of both multi-item scales and single-item measures. These include 1 global health status/quality of life (QoL) scale, 5 functional scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All scales and single-item measures are scored from 0 to 100. This record summarizes the values of the global health status/QoL scale (0 to 100), where higher scores indicate better health/QoL. Therefore, a positive change from baseline is favorable.	Baseline (before first dose), Cycle 3 Day 1 (Week 7) and then every 6 weeks until Cycle 65 Day 1 (Week 193). Each cycle duration is 21 days.
Change From Baseline in EORTC QLQ-LC13: Dyspnea Scale	The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer Module 13 (EORTC QLQ-LC13) is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The 13 items of the LC13 include 1 multi-item scale (dyspnea) and 9 single items (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, and pain in other parts). Each item uses a 4-point Likert scale (1=not at all, 4=very much). Scores for both the dyspnea scale and single items are transformed to a 0-100 scale. This record summarizes the values of the dyspnea scale (0 to 100), where higher scores indicate greater symptom burden. Therefore, a negative change from baseline is a favorable outcome.	Baseline (before first dose), Cycle 3 Day 1 (Week 7) and then every 6 weeks until Cycle 65 Day 1 (Week 193). Each cycle duration is 21 days.
Change From Baseline in EQ-5D-5L: EQ VAS	The EuroQol 5-Dimension 5-Level (EQ-5D-5L) is a standardized, generic instrument to measure health-related quality of life (HRQoL). It consists of two components: a descriptive system and a visual analogue scale. The descriptive system includes five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each rated on five levels of severity (1=no problems, 5=extreme problems). The EuroQol visual analogue scale (EQ VAS) is a 0-100 scale for self-rated overall health, where 0 represents the worst imaginable health and 100 the best imaginable health. This record summarizes the values of the EQ VAS (0 to 100), where higher scores indicate better health. Therefore, a positive change from baseline is favorable.	Baseline (before first dose), Cycle 3 Day 1 (Week 7) and then every 6 weeks until Cycle 65 Day 1 (Week 193). Each cycle duration is 21 days.
Change From Baseline in NCCN FACT-FBrSI: Total Composite Score	The National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy - Brain Symptom Index (NCCN FACT-FBrSI) was used to assess changes in symptoms potentially associated with brain metastases in this study. The NCCN FACT-FBrSI contains 24 items with a 7-day recall period and includes the following subscales: Disease-related symptoms - physical (12 items), Disease-related symptoms - emotional (5 items), Treatment side effects (5 items) and Function/well-being (2 items). Each item uses a 5-point Likert-type scale (0 = Not at all; 4 = Very much). Negatively worded items are reverse scored so that higher scores consistently indicate better symptom status and well-being. The total composite score is the sum of all 24 items and ranges from 0 to 96, with higher scores indicating better symptom status and well-being. An increase in the total composite score from baseline indicates a favorable outcome, while a decrease indicates an unfavorable outcome.	Baseline (before first dose), Cycle 3 Day 1 (Week 7) and then every 6 weeks until Cycle 65 Day 1 (Week 193). Each cycle duration is 21 days.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2021
• Primary Completion (Actual): October 12, 2023
• Study Completion (Actual): May 22, 2025

Study Registration Dates

• First Submitted: December 18, 2020
• First Submitted That Met QC Criteria: December 18, 2020
• First Posted (Actual): December 21, 2020

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; INC280; capmatinib; MET mutation; Non small cell lung cancer; MET exon14; Epidermal growth factor receptor wild type; ALK negative; Non small cell carcinoma; EGFTwt
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; capmatinib
• Other Study ID Numbers: CINC280A2204

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: No
• Studies a U.S. FDA-regulated device product: No