For health care professionals outside the US.

The GEOMETRY clinical trial program GEOMETRY is a group of clinical trials designed to study an investigational treatment for malignancies that harbor mesenchymal-epithelial transition (MET) dysregulation, including advanced non-small cell lung cancer (NSCLC).
The goal of the GEOMETRY program is to determine the possible treatment benefits and the safety of capmatinib (INC280), an oral c-MET inhibitor.
Incidence of c-MET amplification and c-MET mutation in NSCLC1-4
Incidence of c-MET amplification and mutation in NSCLC

*Patients with adenocarcinoma with c-MET mutation leading to exon 14 alterations.3,4
The trials are open to adults with advanced NSCLC throughout the world.
Countries currently enrolling patients are5: Argentina, Austria, Belgium, Brazil, Canada, France, Germany, Israel, Italy, Japan, Lebanon, Mexico, Netherlands, Norway, Poland, Russian Federation, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, and United States.
About GEOMETRYmono-15,6
  • Phase 2, non-randomized, open-label, multicenter, 5-cohort trial
  • Investigating efficacy of oral c-MET inhibitor INC280 (capmatinib)
  • Enrolling adult patients with epidermal growth factor receptor (EGFR) wild-type, anaplastic lymphoma kinase (ALK)-negative, advanced NSCLC harboring c-MET dysregulation (amplification or mutation)
Study design5,6 Patients are divided into 5 cohorts depending on c-MET gene copy number (GCN) or c-MET dysregulation (amplification or mutation). See the schema below:
GEOMETRY mono study design schema
GEOMETRY mono study design schema
End points 
Primary end point5
Overall response rate
Trial definition: The proportion of patients with a best overall response defined as complete response (CR) or partial response (PR) by Blinded Independent Review Committee (BIRC) assessment per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Key secondary end point5
Duration of response
Trial definition: The time from the date of the first documented CR or PR by BIRC per RECIST 1.1 to the first documented progression or death due to any cause for patients with PR or CR.
Other secondary end points5
  • Overall response rate (CR + PR) per RECIST 1.1 by investigator assessment
  • Duration of response per RECIST 1.1 by investigator assessment
  • Time to response per RECIST 1.1 by both BIRC and investigator assessment
  • Disease control rate per RECIST 1.1 by both BIRC and investigator assessment
  • Progression-free survival per RECIST 1.1 by both BIRC and investigator assessment
  • Overall survival defined as time from first dose to death due to any cause
  • Incidence of adverse events and serious adverse events, change in vital signs, laboratory results (hematology, blood chemistry, and urinalysis) and electrocardiogram
  • Cmax, Cmin, and plasma concentration-time profiles of capmatinib (INC280) and metabolite CMN288
Inclusion criteria5 
  • Stage IIIB or IV NSCLC (any histology) at the time of trial entry
  • Histologically or cytologically confirmed diagnosis of NSCLC that is:
  • EGFR wild-type as per patient standard of care by a validated test
  • AND ALK-negative rearrangement as part of the patient standard of care by a validated test
  • AND (by central assessment) either:
  • Cohort 1: pretreated patients with c-MET GCN ≥6, or
  • Cohort 2: pretreated patients with c-MET GCN ≥4 and <6, or
  • Cohort 3: pretreated patients with c-MET GCN <4, or
  • Cohort 4: pretreated patients with c-MET mutation regardless of GCN, or
  • Cohort 5: treatment-naive patients with c-MET dysregulation
  • To be eligible for Cohorts 1-4, patients must have failed 1 or 2 prior lines of systemic therapy for advanced or metastatic disease
  • To be eligible for Cohort 5, patients must not have received any systemic therapy for advanced or metastatic disease
    • At least 1 measurable lesion as defined by RECIST 1.1
    • Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤1 (Common Terminology Criteria for Adverse Events v 4.03). Patients with any grade of alopecia are allowed to enter the trial
    • Patients must have adequate organ function
    • Eastern Cooperative Oncology Group performance status of 0 or 1. Details and other protocol-defined inclusion criteria may apply

Exclusion criteria5 
  • Prior treatment with crizotinib or any other c-MET or hepatocyte growth factor inhibitor
  • Patients with characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to, exon 19 deletions and exon 21 mutations
  • Patients with characterized ALK-positive rearrangement
  • Clinically significant, uncontrolled heart diseases
  • Patients receiving treatment with medications that cannot be discontinued at least 1 week prior to first INC280 treatment and for the duration of the trial
  • Strong and moderate inhibitors of CYP3A4
  • Strong inducers of CYP3A4
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of INC280
  • Patients receiving treatment with any enzyme-inducing anticonvulsant

Other inclusion and exclusion criteria apply.


For more information
For additional information on Novartis clinical trials, please contact your local Novartis medical representative. identifier: NCT02414139.5


  1. Cappuzzo F, Marchetti A, Skokan M, et al. Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. J Clin Oncol. 2009;27(10):1667-1674.
  2. Go H, Jeon YK, Park HJ, Sung S-W, Seo J-W, Chung DH. High MET gene copy number leads to shorter survival in patients with non-small-cell lung cancer. J Thorac Oncol. 2010;5(3):305-313.
  3. Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511(7511):543-550. doi:10.1038/nature13385.
  4. Frampton GM, Ali SM, Rosenzweig M, et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov. 2015;5(8):850-859. doi:10.1158/2159-8290.CD-15-0285.
  5. Novartis Pharmaceuticals. Clinical study of oral cMET inhibitor INC280 in adult patients with EGFR wild-type advanced non-small cell lung cancer. Bethesda, MD: National Library of Medicine (US). NLM Identifier: NCT02414139. Accessed April 17, 2017.
  6. Data on file. Novartis Pharmaceuticals Corporation.