Clinical Trials List
Protocol NumberCINC280B2201
NCT Number(ClinicalTrials.gov Identfier)NCT02468661
2016-03-07 - 2018-12-31
Phase II
Terminated2
ICD-10C34
Malignant neoplasm of bronchus and lung
A phase Ib/II, open-label, multicenter trial with oral cMET inhibitor INC280 alone and in combination with erlotinib versus platinum with pemetrexed in adult patients with EGFR mutated, cMET-amplified, locally advanced/metastatic non-small cell lung cancer (NSCLC) with acquired resistance to prior EGFR tyrosine kinase inhibitor (EGFR TKI)
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
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Sponsor
Novartis Pharmaceuticals
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ming-Mo Hou Division of Hematology & Oncology
- 楊振達 Division of Thoracic Medicine
- Cheng-Ta Yang Division of Thoracic Medicine
- Shih-Hong Li Division of Thoracic Medicine
- Chien-Ying Liu Division of Thoracic Medicine
- Chih-Hung Chen Division of Thoracic Medicine
- Chih-Hung Chen Division of Thoracic Medicine
- Chih-Liang Wang Division of Thoracic Medicine
- 吳振德 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Chia-Chi Lin Division of Hematology & Oncology
- 陳冠宇 Division of Hematology & Oncology
- James Chih-Hsin Yang Division of Hematology & Oncology
- JIN-YUAN SHIH Division of Hematology & Oncology
- 許嘉林 Division of Hematology & Oncology
- 李育麟 Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- 廖唯昱 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
advanced/metastatic non-small cell lung cancer (NSCLC)
Objectives
The purpose of this study is to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of INC280 in combination with erlotinib in the Phase Ib of this study, and to assess the anti-tumor activity and safety of INC280 alone, and in combination with erlotinib, versus platinum with pemetrexed in the Phase II of this study, in adult patients with EGFR mutated, cMET amplified, advanced/metastatic non-small cell lung cancer with acquired resistance to prior EGFR TKI.
Test Drug
INC280 (capmatinib)
Active Ingredient
INC280 (capmatinib)
Dosage Form
Tablet
Dosage
100, 200
Endpoints
Efficacy assessments
Tumor assessment by investigator’s assessment per RECIST v1.1, measured every 6 weeks
(i.e., every 2 cycles)
Safety assessments
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs
and ECGs
Other assessments
Plasma concentration vs time profiles, plasma PK parameters
Exploratory biomarkers
Tumor assessment by investigator’s assessment per RECIST v1.1, measured every 6 weeks
(i.e., every 2 cycles)
Safety assessments
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs
and ECGs
Other assessments
Plasma concentration vs time profiles, plasma PK parameters
Exploratory biomarkers
Inclution Criteria
Common inclusion criteria for Phase Ib and Phase II:
● ≥ 20 years of age at the time of informed consent.
● Locally advanced or metastatic NSCLC (stage IIIB and is not a candidate for definitive
multimodality therapy or IV) other than predominantly squamous cell histology harboring
EGFR mutation known to be associated with EGFR TKI drug sensitivity (exon 19 deletion or
L858R).
● Patients must meet the criteria for acquired resistance to EGFR TKI (either 1st generation
(e.g., erlotinib, gefitinib) or 2nd generation (e.g., afatinib)) defined as:
Documented clinical benefit (CR, PR, or SD (≥ 6 months) as per RECIST)
Demonstrated progression, while on continuous treatment, or within 30 days since the date
of last administration of EGFR TKI, per RECIST
● 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.
● Life expectancy ≥ 3 months.
● ECOG performance status (PS) ≤ 1.
● Patients must have adequate organ function including the following laboratory values at
the screening visit:
● Hemoglobin ≥ 9 g/dL
● Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
● Calculated creatinine clearance (using Cockcroft-Gault formula) > 45 mL/min
● Total bilirubin ≤ 1.5 x ULN
● Aspartate transaminase (AST) ≤ 3 x ULN, except for patients with liver metastasis,
who may only be included if AST ≤ 5 x ULN
● Alanine transaminase (ALT) ≤ 3 x ULN, except for patients with liver metastasis, who
may only be included if ALT ≤ 5 x ULN
● Fasting plasma glucose ≤ 175 mg/dL (≤ 9.8 mmol/L)
● Alkaline phosphatase (ALP) ≤ 5.0 x ULN
● Asymptomatic serum amylase ≤ grade 2. Patients with grade 1 or grade 2 serum
amylase at the beginning of the study must be confirmed to have no signs and/or
symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase,
abnormal imaging findings of pancreas, etc.)
● Serum lipase ≤ ULN
● Patients enrolled must have the following laboratory values within the laboratory
normal limits or corrected to within normal limits with supplements during screening:
● Potassium
● Magnesium
● Phosphorus
● Total calcium (corrected for serum albumin)
● Written informed consent must be obtained prior to any screening procedures
● Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
● ≥ 20 years of age at the time of informed consent.
● Locally advanced or metastatic NSCLC (stage IIIB and is not a candidate for definitive
multimodality therapy or IV) other than predominantly squamous cell histology harboring
EGFR mutation known to be associated with EGFR TKI drug sensitivity (exon 19 deletion or
L858R).
● Patients must meet the criteria for acquired resistance to EGFR TKI (either 1st generation
(e.g., erlotinib, gefitinib) or 2nd generation (e.g., afatinib)) defined as:
Documented clinical benefit (CR, PR, or SD (≥ 6 months) as per RECIST)
Demonstrated progression, while on continuous treatment, or within 30 days since the date
of last administration of EGFR TKI, per RECIST
● 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.
● Life expectancy ≥ 3 months.
● ECOG performance status (PS) ≤ 1.
● Patients must have adequate organ function including the following laboratory values at
the screening visit:
● Hemoglobin ≥ 9 g/dL
● Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
● Calculated creatinine clearance (using Cockcroft-Gault formula) > 45 mL/min
● Total bilirubin ≤ 1.5 x ULN
● Aspartate transaminase (AST) ≤ 3 x ULN, except for patients with liver metastasis,
who may only be included if AST ≤ 5 x ULN
● Alanine transaminase (ALT) ≤ 3 x ULN, except for patients with liver metastasis, who
may only be included if ALT ≤ 5 x ULN
● Fasting plasma glucose ≤ 175 mg/dL (≤ 9.8 mmol/L)
● Alkaline phosphatase (ALP) ≤ 5.0 x ULN
● Asymptomatic serum amylase ≤ grade 2. Patients with grade 1 or grade 2 serum
amylase at the beginning of the study must be confirmed to have no signs and/or
symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase,
abnormal imaging findings of pancreas, etc.)
● Serum lipase ≤ ULN
● Patients enrolled must have the following laboratory values within the laboratory
normal limits or corrected to within normal limits with supplements during screening:
● Potassium
● Magnesium
● Phosphorus
● Total calcium (corrected for serum albumin)
● Written informed consent must be obtained prior to any screening procedures
● Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
Exclusion Criteria
Specific exclusion criteria for Phase II:
● Patients with history of severe hypersensitivity reaction to platinum containing drugs,
pemetrexed or any known excipients of these drugs.
● Prior treatment with any of the following agents
● Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor.
● Concomitant EGFR TKI and platinum based chemotherapy as first line regimen.
● Platinum-based chemotherapy as first line treatment.
Common exclusion criteria for Phase Ib and Phase II:
● Prior treatment with any 3rd generation EGFR TKI (e.g., CO1686, AZD9192).
● Symptomatic central nervous system (CNS) metastases
● 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).
● Presence of clinically significant ophthalmologic abnormalities
●Strong or moderate inhibitors of CYP3A4; strong or moderate inducers of CYP3A4; proton
pump inhibitors, within 1 week prior to start of treatment with INC280 and for the duration of
the study
● Pregnant or nursing (lactating)women
● Patients with history of severe hypersensitivity reaction to platinum containing drugs,
pemetrexed or any known excipients of these drugs.
● Prior treatment with any of the following agents
● Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor.
● Concomitant EGFR TKI and platinum based chemotherapy as first line regimen.
● Platinum-based chemotherapy as first line treatment.
Common exclusion criteria for Phase Ib and Phase II:
● Prior treatment with any 3rd generation EGFR TKI (e.g., CO1686, AZD9192).
● Symptomatic central nervous system (CNS) metastases
● 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).
● Presence of clinically significant ophthalmologic abnormalities
●Strong or moderate inhibitors of CYP3A4; strong or moderate inducers of CYP3A4; proton
pump inhibitors, within 1 week prior to start of treatment with INC280 and for the duration of
the study
● Pregnant or nursing (lactating)women
The Estimated Number of Participants
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Taiwan
6 participants
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Global
135 participants
