Study of Capmatinib Efficacy in Comparison With Docetaxel in Previously Treated Participants With Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation

NCT04427072 | Terminated Phase 3 Results

• 2 other identifiers: CINC280A23012020-001578-31
• Study Type: interventional
• Target: 22
• Locations: 18 countries
• Sites: 43

Brief 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. 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.

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; MET exon14 deletion; METex14; METex14del; MET∆ex14; EGFRwt; Epidermal growth factor receptor wild type; ALK negative; docetaxel

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Up to approximately 21 months

• Overall Response Rate (ORR) Per RECIST 1.1 by Investigator

  Up to approximately 21 months

• Time to Response (TTR) Per RECIST 1.1 by BIRC

  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

  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

  From first documented response to first documented progression or death due to any cause, whichever came first, assessed up to approximately 21 months

Study Arms (2)

Capmatinib

EXPERIMENTAL

400 mg, capmatinib tablets, administered orally twice daily

Drug: Capmatinib

Docetaxel

ACTIVE COMPARATOR

Docetaxel 75 mg/m\^2 solution administered by intravenous infusion on Day 1 of every 21-day cycle

Drug: Docetaxel

Interventions

Capmatinib DRUG

400 mg, capmatinib tablets, administered orally twice daily

Also known as: INC280

Capmatinib

Docetaxel DRUG

Docetaxel 75 mg/m\^2 by intravenous infusion every 21 days

Docetaxel

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \. 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (43)

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Barretos, São Paulo, 14784 400, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01246 000, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 04014-002, Brazil

Location

Novartis Investigative Site

Pleven, 5800, Bulgaria

Location

Novartis Investigative Site

Sofia, 1303, Bulgaria

Location

Novartis Investigative Site

Sofia, 1407, Bulgaria

Location

Novartis Investigative Site

Caen, 14021, France

Location

Novartis Investigative Site

Paris, 75231, France

Location

Novartis Investigative Site

Pierre-Bénite, 69495, France

Location

Novartis Investigative Site

Gauting, Bavaria, 82131, Germany

Location

Novartis Investigative Site

Regensburg, Bavaria, 93053, Germany

Location

Novartis Investigative Site

Berlin, 13125, Germany

Location

Novartis Investigative Site

Berlin, 14165, Germany

Location

Novartis Investigative Site

Cologne, 50937, Germany

Location

Novartis Investigative Site

Oldenburg, 26121, Germany

Location

Novartis Investigative Site

Törökbálint, Pest County, 2045, Hungary

Location

Novartis Investigative Site

Budapest, 1121, Hungary

Location

Novartis Investigative Site

Pune, Maharashtra, 411013, India

Location

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110076, India

Location

Novartis Investigative Site

Vellore, Tamil Nadu, 632 004, India

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Roma, RM, 00128, Italy

Location

Novartis Investigative Site

Vilnius, LT-08660, Lithuania

Location

Novartis Investigative Site

Kuala Lumpur, Kuala Lumpur, 50586, Malaysia

Location

Novartis Investigative Site

Kuantan, Pahang, 25100, Malaysia

Location

Novartis Investigative Site

Pulau Pinang, 10990, Malaysia

Location

Novartis Investigative Site

Nijmegen, 6500HB, Netherlands

Location

Novartis Investigative Site

Lisbon, 1769 001, Portugal

Location

Novartis Investigative Site

Matosinhos Municipality, 4454 513, Portugal

Location

Novartis Investigative Site

Nizhny Novgorod, 603081, Russia

Location

Novartis Investigative Site

Omsk, 644013, Russia

Location

Novartis Investigative Site

Pushkin Saint Petersburg, 196603, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197022, Russia

Location

Novartis Investigative Site

Port Elizabeth, Western Cape, 6045, South Africa

Location

Novartis Investigative Site

Seoul, 05505, South Korea

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Oviedo, Principality of Asturias, 33011, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Valencia, 46026, Spain

Location

Novartis Investigative Site

Songkhla, Hat Yai, 90110, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Hanoi, 100000, Vietnam

Location

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

capmatinib; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 11, 2020
• Study Start: September 25, 2020
• Primary Completion: February 15, 2023
• Study Completion: November 6, 2023
• Last Updated: May 16, 2025
• Results First Posted: January 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

LI (1); IT (2); BE (1); RU (4); ZA (1); PT (2); BR (3); VN (1); HU (2); NL (1); FR (3); IN (3); BU (3); KR (1); DE (6); MY (3); ES (4); TH (2)