Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (Geometry Mono-1)

• Register: ClinicalTrials.gov
• Last refreshed on: 24 April 2023
• Main ID: NCT02414139
• Date of registration: 31/03/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (Geometry Mono-1)
• Scientific title: A Phase II, Multicenter Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type (wt), Advanced Non-small Cell Lung Cancer (NSCLC)(Geometry Mono-1)
• Date of first enrolment: June 11, 2015
• Target sample size: 373
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02414139
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Argentina, Austria, Belgium, Brazil, Canada, France, Germany, Israel, Italy, Japan, Korea, Republic of, Lebanon, Mexico, Netherlands, Norway, Poland, Russian Federation, Singapore, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

- Stage IIIB or IV NSCLC (any histology) at the time of study entry

- Histologically or cytologically confirmed diagnosis of NSCLC that is:

1. EGFR wt as per patient standard of care by a validated test

2. AND ALK-negative rearrangement as part of the patient standard of care by a
validated test

3. AND (by central assessment) either:

- Cohort 1: Pre-treated patients with cMET GCN = 6 or

- Cohort 2: Pre-treated patients with cMET GCN =4 and < 6, or

- Cohort 3: Pre-treated patients with cMET GCN < 4, or

- Cohort 4: Pre-treated patients with cMET mutations regardless of cMET GCN,
or

- Cohort 5: Treatment-naïve patients with cMET dysregulation, or

- Cohort 6: Pre-treated patients with either cMET GCN = 10 without cMET
mutations or cMET mutations regardless of cMET GCN, or

- Cohort 7: Treatment-naïve patients with cMET mutations regardless of cMET
GCN

- To be eligible for Cohorts 1-4, patients must have failed one or two prior lines of
systemic therapy for advanced/metastatic disease

- To be eligible for Cohort 6, patients must have failed one prior line of systemic
therapy for advanced/metastatic disease

- To be eligible for Cohort 5 and Cohort 7, patients must not have received any systemic
therapy for advanced/metastatic disease

- At least one measurable lesion as defined by RECIST 1.1

- Patients must have recovered from all toxicities related to prior anticancer therapies
to grade = 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter
the study.

- Patients must have adequate organ function

- ECOG performance status (PS) of 0 or 1 Details and other protocol-defined inclusion
criteria may apply

Exclusion Criteria:

- Prior treatment with crizotinib, or any other cMET or HGF 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 study:

- Strong inducers of CYP3A4

- Impairment of GI function or GI disease that may significantly alter the absorption of
INC280

- Patients receiving treatment with any enzyme-inducing anticonvulsant

- Applicable to Cohorts 1-4 and Cohort 6 only: Previous anti-cancer and investigational
agents within 4 weeks or = 5 x half-life of the agent (whichever is longer) before
first dose

- Pregnant or nursing women

- Women of child-bearing potential, unless they are using highly effective methods of
contraception

- Sexually active males unless they use a condom during intercourse

- Presence or history of interstitial lung disease or interstitial pneumonitis,
including clinically significant radiation pneumonitis

Other protocol-defined exclusion criteria may apply



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Carcinoma, Non-Small-Cell Lung

Intervention(s)

Drug: INC280 (capmatinib)

Primary Outcome(s)

Overall Response Rate (ORR) [Time Frame: at least 18 weeks]

Secondary Outcome(s)

Duration of Response (DOR) - Key Secondary [Time Frame: at least 18 weeks]

Disease Control Rate (DCR) [Time Frame: at least 18 weeks]

Duration of Response (DOR) [Time Frame: at least 18 weeks]

Overall Response Rate (ORR) [Time Frame: at least 18 weeks]

Cmax, Cmin and plasma concentration-time profiles of INC280 [Time Frame: 6 weeks]

Number of patients with incidence of adverse events and serious adverse events, change in vital signs, laboratory results (hematology, blood chemistry, and urinalysis) and ECG. [Time Frame: at least 18 weeks]

Progression-free Survival (PFS) [Time Frame: at least 18 weeks]

Time to Response (TTR) [Time Frame: at least 18 weeks]

Overall Survival (OS) [Time Frame: at least 18 weeks]

Secondary ID(s)

2014-003850-15

CINC280A2201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors