Study of Safety and Efficacy of EGFR-TKI EGF816 in Combin... | NCT02335944 | Trialant
NCT02335944
Sponsor
Novartis Pharmaceuticals
Status
Terminated
Last Update Posted
Jun 18, 2023Actual
Enrollment
177Actual
Phase
Phase 1Phase 2
Conditions
Non Small Cell Lung Cancer
Interventions
Capmatinib
Nazartinib
Countries
United States
Australia
Canada
France
Germany
Italy
Norway
Singapore
South Korea
Spain
Taiwan
Protocol Section
Identification Module
NCT ID
NCT02335944
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CINC280X2105C
Secondary IDs
ID
Type
Description
Link
2014-000726-37
EudraCT Number
Brief Title
Study of Safety and Efficacy of EGFR-TKI EGF816 in Combination With cMET Inhibitor INC280 in Adult Patients With EGFR Mutated Non Small Cell Lung Cancer.
Official Title
A Phase Ib/II, Multicenter, Open-label Study of EGF816 in Combination With INC280 in Adult Patients With EGFR Mutated Non-small Cell Lung Cancer.
Acronym
Not provided
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
May 2023
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Company decision
Expanded Access Info
No
Start Date
Jan 13, 2015Actual
Primary Completion Date
Nov 10, 2020Actual
Completion Date
Nov 10, 2020Actual
First Submitted Date
Oct 9, 2014
First Submission Date that Met QC Criteria
Jan 7, 2015
First Posted Date
Jan 12, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Jan 10, 2023
Results First Submitted that Met QC Criteria
May 24, 2023
Results First Posted Date
Jun 18, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 24, 2023
Last Update Posted Date
Jun 18, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study was to determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of nazartinib (EGF816) in combination with capmatinib (INC280) and to estimate the preliminary anti-tumor activity of nazartinib in combination with capmatinib in participants with advanced non-small cell lung cancer (NSCLC) with documented EGFR mutation.
Detailed Description
This study was designed as a Phase Ib/II, multi-center, open-label study starting with a Phase Ib dose escalation part followed by a Phase II expansion part. Oral nazartinib (once daily) and capmatinib (twice daily) was administered on a continuous schedule until participant experienced unacceptable toxicity, progressive disease (PD) and/or treatment was discontinued at the discretion of the investigator or withdrawal of consent/opposition to use data/biological samples. Study treatment could be continued beyond Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) defined PD, in the judgment of the investigator, when there was evidence of clinical benefit and the subject wished to continue with the study treatment.
In Phase Ib part, participants with NSCLC harboring EGFR activating mutations were enrolled. At the end of the Phase Ib part, once the MTD or RP2D of nazartinib in combination with capmatinib was declared, additional participants with NSCLC were enrolled in the Phase II part in order to assess the preliminary anti-tumor activity of nazartinib in combination with capmatinib. Participants with locally advanced or metastatic NSCLC were assigned into different groups according to their resistance mechanisms.
As per the Protocol amendment 7, an additional group (Group 5) was included into study CINC280X2105C, which was intended to support study CINC280L12301. After thorough and careful assessment of study CINC280L12301 enrollment status, projected study completion timelines, and the changing clinical landscape, Novartis made the decision to discontinue the study. Importantly, this decision was not driven by safety concerns; no new safety signals were observed in the study participants or in the ongoing capmatinib program. As such, Group 5 data was no longer needed and the new arm in study CINC280X2105C was not opened as planned.
Conditions Module
Conditions
Non Small Cell Lung Cancer
Keywords
non small cell lung cancer
NSCLC
EGF816
INC280
tyrosine kinase inhibitor
c-MET
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
177Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Phase IB part- NSCLC with EGFR activating mutations
Experimental
NSCLC participants who have previously documented EGFR mutation and progressed on EGFR TKI treatment. Participants were treated at a starting dose of 50 mg once a day for EGF816 and 200 mg twice a day for INC280 in fasted state
Drug: Capmatinib
Drug: Nazartinib
Phase II- Group 1 (EGFRmut, any T790M, any MET, 2/4L antineoplastic, EGFR TKI resistant)
Experimental
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received one to three lines of systemic antineoplastic therapy prior to study entry including one line maximum of first or second generation EGFR TKI and who progressed on this EGFR TKI treatment line. Participants were treated at the RP2D of INC280 and EGF816 in fasted state
Drug: Capmatinib
Drug: Nazartinib
Phase II- Group 2 (EGFRmut, de novo T790M, any MET, 1/3L antineoplastic, EGFR TKI naïve)
Experimental
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who are treatment naïve or received maximum 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated at the RP2D of INC280 and EGF816 in fasted state
Drug: Capmatinib
Drug: Nazartinib
Phase II- Group 3 (EGFRmut, T790M negative, any MET, 1L antineoplastic)
Experimental
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic systemic therapy prior to study entry. Participants were treated at the RP2D of INC280 and EGF816 in fasted state
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Capmatinib
Drug
In the Phase 1, capmatinib was administered orally, twice per day, at a dose of 200 mg or 400 mg, in fasted state.
In the Phase II, participants received capmatinib at the RP2D (400 mg twice per day) in fasted state (Groups 1, 2 and 3) or fed state (Group 4).
Participants in Phase II Group 5 were to start with capmatinib monotherapy (fasted or fed state) and then would have had the opportunity to continue with the combination of nazartinib and capmatinib (fasted or fed state).
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs)
Number of participants with DLTs in the Phase Ib part. A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment with EGF816 in combination with INC280 during the escalation part of the study (Phase Ib)
Up to first 28 days of treatment
Phase II Group 1, 2 and 3: Overall Response Rate (ORR) by Investigator's Assessment Per RECIST 1.1
ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) determined by investigator's assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). ORR was assessed in Group 1, 2 and 3 (Phase II part).
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 diameters of all target lesions, taking as reference the baseline sum of diameters.
Up to approximately 4 years
Phase II Group 4: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Number of participants in Group 4 (Phase II part) with AEs and SAEs. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
From start of treatment up to 30 days after last dose of study treatment, assessed up to 3.7 years
Phase II Group 4: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618
Secondary Outcomes
Measure
Description
Time Frame
Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618
Number of participants in Phase Ib with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 .
From start of treatment until end of treatment, assessed up to approximately 5 years
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key Inclusion criteria:
- Participants in Phase Ib and Phase II Groups 1 to 4: histologically documented, locally advanced or recurrent (stage IIIB who were not eligible for combined modality treatment) or metastatic (Stage IV) NSCLC.
Participants in Phase II Group 5: stage IIIB/IIIC (not amenable to curative surgery, chemoradiation or radiation) or stage IV NSCLC
Participants in Phase Ib and Phase II Groups 1 to 4: locally documented EGFR mutation L858R and/or ex19del, or a characterized de novo EGFR T790M mutation (or other rare activating mutations that confer sensitivity to 1st and 2nd generation EGFR inhibitors (e.g. L861Q, G719X, S768I), or a characterized de novo EGFRT790M mutation.
Presence of at least one measurable lesion according to RECIST v.1.1
ECOG performance status ≤1
Participants had to be screened for HBV. Participants who were either HBsAg positive or HBV-DNA positive had to be willing and able to take antiviral therapy 1-2 weeks prior to 1st dose of EGF816 treatment and continue on antiviral therapy for at least 4 weeks after the last dose of EGF816.
Participants had to be screened for HCV. Participants had to have negative hepatitis C antibody (HCV Ab) or were HCV Ab positive but with an undetectable level of HCV-RNA. Note: participants with detectable HCV-RNA were not eligible for the study.
Phase Ib only: documented progression of disease according to RECIST v1.1 while on continuous treatment with EGFR TKI (e.g.: erlotinib, gefitinib or afatinib).
Phase II Group 1 (EGFRmut, any T790M, any c-MET, 2/4L antineoplastic, EGFR TKI resistant) only: Participants demonstrated a documented clinical benefit (CR (any duration), PR (any duration), or SD for at least 6 months) on prior EGFR TKI (e.g. erlotinib, gefitinib or afatinib, and subsequently demonstrated progression according to RECIST v1.1.
Phase II Group 2 (EGFRmut, de novo T790M, any c-MET, 1/3L antineoplastic, EGFR TKI naïve) only: Advanced NSCLC participants who were not previously treated with any therapy known to inhibit EGFR and harbor de novo T790M mutation .
Phase II Group 3 (EGFRmut, T790M negative, any c-MET, 1L antineoplastic) only: participants had to harbor an EGFR activating mutation and had to be naïve from any line of systemic antineoplastic therapy in the advanced setting.
Phase II Group 4 (EGFRmut, any T790M, any c-MET, 1L (treatment-naïve), 2//3L antineoplastic): All participants had to harbor an EGFR activating mutation and 2/3L participants had to have failed (defined as intolerance to treatment or documented disease progression) a maximum of 2 prior lines of antineoplastic therapy in the advanced setting
Phase II Group 5 only: Histologically or cytologically confirmed diagnosis of NSCLC (excluding squamous cell carcinoma) with all the following:
EGFR mutations known to be associated with EGFR TKI sensitivity. This had to be assessed as part of the participant standard of care by a validated test for EGFR mutations, as per local regulations. Exon 19 del, L858R, either alone or in combination with other EGFR sensitivity mutation assessed by a Clinical Laboratory Improvement Amendments (CLIA) certified USA laboratory or an accredited local laboratory outside the USA had to be documented in the participant source documents before the participant consented for pre-screening for MET amplification status.
EGFR T790M negative status for participants who had progressed on first or second generation EGFR TKI, or third generation EGFR TKI other than osimertinib, as per tissue-based result from a CLIA-certified USA laboratory or an accredited local laboratory outside of the USA, by a validated test according to local regulations.
MET gene amplification defined as: Gene copy number (GCN) ≥ 5 per tissue-based result from a CLIA-certified USA laboratory or an accredited local laboratory outside of the USA by a test that is validated according to local regulations with results documented in the participant source documents.
Histological transformation from NSCLC into small cell lung cancer (SCLC) following previous EGFR TKI treatment were excluded.
Participants had to have progressed on one prior line of therapy either to first/second generation EGFR TKIs, osimertinib or other third generation EGFR TKIs for advanced/metastatic disease (stage IIIB/IIIC [not amenable to curative surgery, chemoradiation or radiation or stage IV NSCLC).
Participants had to have a life expectancy of at least 3 months.
Key exclusion Criteria:
Phase Ib:
More than one previous treatment line with erlotinib, gefitinib or afatinib
Previous treatment with any investigational agent known to inhibit EGFR (mutant or wild-type)
Participants who had received more than three prior lines of antineoplastic therapies (including EGFR TKI) in advanced setting.
Phase II Group 1 (EGFRmut, any T790M, any c-MET, 2/4L antineoplastic, EGFR TKI resistant):
More than 3 prior lines of systemic antineoplastic therapies (including EGFR TKI) in the advanced setting
More than 1 previous treatment line with 1st or 2nd generation EGFR TKI (e.g. erlotinib, gefitinib, afatinib) in the advanced setting
Previous treatment with an investigational or marketed 3rd generation EGFR TKI (e.g. AZD9291, CO-1686, ASP8273, EGF816)
Previous treatment with an investigational or marketed agent known to inhibit EGFR (e.g. EGF monoclonal antibody therapy, dual TKI inhibitor).
Phase II Group 2 (EGFRmut, de novo T790M, any c-MET, 1/3L antineoplastic, EGFR TKI naïve):
More than two previous treatment lines of systemic antineoplastic therapies in the advanced setting
Previous treatment with an investigational or marketed agent that inhibits EGFR. EGFR inhibitors include (but not limited to) all generations of EGFR TKI (e.g.erlotinib, gefitinib, afatinib, AZD9291, CO-1686, ASP8273, EGF816) or other anti-EGFR or EGFR monoclonal antibody therapy or dual TKI inhibitors.
Phase II Group 3 (EGFRmut, T790M negative, any c-MET, 1L antineoplastic):
De novo EGFR T790M mutation identified by central assessment
Previous treatment with any systemic antineoplastic therapy in the advanced setting (NSCLC stage IIIB or IV. Participants who received only one cycle of antineoplastic therapy in the advanced setting were allowed).
Phase II Group 4 (EGFRmut, any T790M, any c-MET, 1/3L antineoplastic):
More than 2 prior lines of systemic antineoplastic therapies in the advanced setting
Previous treatment with an investigational or marketed 3rd generation EGFR TKI (e.g. AZD9291, CO-1686, ASP8273, EGF816)
Previous treatment with an investigational or marketed agent known to inhibit EGFR (e.g. EGF monoclonal antibody therapy, dual TKI inhibitor).
Previous treatment with a c-MET inhibitor or HGF-targeting therapy.
Participants with symptomatic brain metastases.
Phase II Group 5: 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.
Presence or history of another malignancy. Exception: Participants who had been disease-free for 3 years, or participants with a history of adequately treated in-situ carcinoma of the uterine cervix, completely resected basal or squamous cell carcinoma, non-melanomatous cancer of skin, history of stage IA melanoma that had been cured, were eligible.
For Phase II Group 5: Presence or history of a malignant disease other than NSCLC that had been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
Undergone a bone marrow or solid organ transplant.
Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory).
For Group 5: Participants with known history of testing positive for human immunodeficiency virus (HIV) infection, and with a history of Acquired ImmunoDeficiency Syndrome (AIDS) defining opportunistic infections in the last 12 months prior to the first dose of study treatment had to be excluded
Participants receiving concomitant immunosuppressive agents or chronic corticosteroids used at the time of study entry except for control of brain metastases, topical applications, inhaled sprays, eye drops or local injections
Participants with clinically significant, uncontrolled cardiovascular disease
Presence or history of interstitial lung disease or interstitial pneumonitis
Participants who had not recovered from all toxicities related to prior anticancer therapies to grade ≤1 (CTCAE v 4.03)
Participants who had out of range laboratory values
Participants who received live vaccines](streamdown:incomplete-link)
Felip E, Metro G, Soo RA, Wolf J, Solomon BJ, Tan DS, Ardizzoni A, Lee DH, Sequist LV, Barlesi F, Ponce-Aix S, Abreu DR, Campelo MRG, Sprauten M, Djentuh LO, Smith N, Jary A, Belli R, Glaser S, Zou M, Cui X, Giovannini M, Yang JC. Capmatinib plus nazartinib in patients with EGFR-mutated non-small cell lung cancer. Eur J Cancer. 2024 Sep;208:114182. doi: 10.1016/j.ejca.2024.114182. Epub 2024 Jun 22.
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.
The screening period began once patients had signed the study informed consent. All screening/baseline evaluations were performed ≤ 28 days before Cycle 1 Day 1.
Recruitment Details
Participants took part in 19 investigative sites in 11 countries. Due to early study termination, Group 5 (Phase II part) was never opened
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
FG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Periods
Title
Milestones
Reasons Not Completed
Treatment Phase
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Oct 20, 2021
Jan 10, 2023
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Hong Kong
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Single Group Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug: Capmatinib
Drug: Nazartinib
Phase II- Group 4 (EGFRmut, any T790M, any MET, 1L (treatment naïve) 2-3L antineoplastic)
Experimental
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who were treatment naïve or failed maximum 2 prior lines of any systemic antineoplastic therapy for advanced disease. Participants were treated at the RP2D of INC280 and EGF816 in fed state
Drug: Capmatinib
Drug: Nazartinib
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L, EGFR TKI resistant)
Experimental
NSCLC participants with previously documented EGFR activating mutation, T790M negative, acquired MET amplification who have progressed on one prior line of therapy for advanced/metastatic NSCLC disease. Participants were to start with INC280 monotherapy (twice a day) and would have had the opportunity to continue to combination of EGF816 (once a day) and INC280 (twice a day) based on radiological disease progression evaluation by investigator's assessment per RECIST 1.1
Drug: Capmatinib
Drug: Nazartinib
Phase IB part- NSCLC with EGFR activating mutations
Phase II- Group 1 (EGFRmut, any T790M, any MET, 2/4L antineoplastic, EGFR TKI resistant)
Phase II- Group 2 (EGFRmut, de novo T790M, any MET, 1/3L antineoplastic, EGFR TKI naïve)
Phase II- Group 3 (EGFRmut, T790M negative, any MET, 1L antineoplastic)
Phase II- Group 4 (EGFRmut, any T790M, any MET, 1L (treatment naïve) 2-3L antineoplastic)
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L, EGFR TKI resistant)
INC280
Nazartinib
Drug
In the Phase 1, nazartinib was administered orally, once a day, at a dose of 50 mg, 75 mg, 100 mg or 150 mg in fasted state.
In the Phase II, participants received nazartinib at the RP2D (100 mg once daily) in fasted state (Groups 1, 2 and 3) or fed state (Group 4). Participants in Phase II Group 5 were to start with capmatinib monotherapy (fasted or fed state) and then would have had the opportunity to continue with the combination of nazartinib and capmatinib (fasted or fed state).
Phase IB part- NSCLC with EGFR activating mutations
Phase II- Group 1 (EGFRmut, any T790M, any MET, 2/4L antineoplastic, EGFR TKI resistant)
Phase II- Group 2 (EGFRmut, de novo T790M, any MET, 1/3L antineoplastic, EGFR TKI naïve)
Phase II- Group 3 (EGFRmut, T790M negative, any MET, 1L antineoplastic)
Phase II- Group 4 (EGFRmut, any T790M, any MET, 1L (treatment naïve) 2-3L antineoplastic)
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L, EGFR TKI resistant)
EGF816
Number of participants with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 in the Group 4 (Phase II part).
From start of treatment until end of treatment, assessed up to 3.6 years
Phase II Group 4: Dose Intensity
Dose intensity, defined as the ratio of total dose received and actual duration, for participants in Group 4 (Phase II part)
From start of treatment until end of treatment, assessed up to 3.6 years
Phase II Group 5: ORR Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) determined by Investigator assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for participants in Group 5 (Phase II part) while on treatment with INC280 monotherapy.
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 diameters of all target lesions, taking as reference the baseline sum of diameters.
Up to approximately 3 years (while on INC280 monotherapy)
Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618
Number of participants in Groups 1, 2 and 3 (Phase II part) with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 .
From start of treatment until end of treatment, assessed up to approximately 4 years
Phase Ib: Dose Intensity
Dose intensity, defined as the ratio of total dose received and actual duration, in Phase Ib participants
From start of treatment until end of treatment, assessed up to approximately 5 years
Phase II Group 1, 2 and 3: Dose Intensity
Dose intensity, defined as the ratio of total dose received and actual duration, in Group 1, 2 and 3 (Phase II)
From start of treatment until end of treatment, assessed up to approximately 4 years
Phase Ib: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment
ORR is defined as percentage of participants with best overall response of PR+CR determined by Investigator's assessment in accordance to RECIST 1.1. ORR was assessed in Phase Ib participants.
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 diameters of all target lesions, taking as reference the baseline sum of diameters.
Up to approximately 5 years
Phase II Group 4: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment
ORR is defined as percentage of participants with best overall response of PR+CR determined by Investigator's assessment in accordance to RECIST 1.1. ORR was assessed in Group 4 (Phase II) 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 diameters of all target lesions, taking as reference the baseline sum of diameters.
Up to approximately 4 years
Phase Ib: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment
PFS is defined as time from date of first dose of study treatment to date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1.or death due to any cause. The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, PFS is censored at the date of last adequate tumor assessment. PFS was assessed in Phase Ib participants
From date of first dose to first documented disease progression or death, assessed up to approximately 5 years
Phase II Groups 1, 2, 3 and 4: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment
PFS is defined as time from date of first dose of study treatment to date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1.or death due to any cause. The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, PFS is censored at the date of last adequate tumor assessment. PFS was assessed in Group 1, 2, 3 and 4 (Phase II)
From date of first dose to first documented disease progression or death, assessed up to approximately 4 years
Phase Ib: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment
TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment in accordance to RECIST 1.1. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. TTR was assessed in Phase Ib participants.
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 diameters of all target lesions, taking as reference the baseline sum of diameters.
From the date of the first dose to the date of first documented response, up to approximately 5 years
Phase II Groups 1, 2, 3 and 4: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment
TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment in accordance to RECIST 1.1. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. TTR was assessed in Group 1, 2, 3 and 4 (Phase II) 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 diameters of all target lesions, taking as reference the baseline sum of diameters.
From the date of the first dose to the date of first documented response, up to approximately 4 years
Phase Ib: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment
DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1 or death due to underlying cancer. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. DOR was assessed in Phase Ib participants 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 diameters of all target lesions, taking as reference the baseline sum of diameters.
From date of first documented response to first documented disease progression or death, assessed up to approximately 5 years
Phase II Groups 1, 2, 3 and 4: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment
DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1 or death due to underlying cancer. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. DOR was assessed in Group 1, 2, 3 and 4 (Phase II) 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 diameters of all target lesions, taking as reference the baseline sum of diameters.
From date of first documented response to first documented disease progression or deaths, assessed up to approximately 4 years
Phase Ib: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment
DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease (SD) determined by Investigator assessment in accordance to RECIST 1.1. DCR was assessed in Phase Ib participants 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 diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
Up to approximately 5 years
Phase II Group 1, 2 3 and 4: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment
DCR is defined as the percentage of participants with best overall response of CR, PR, or SD determined by Investigator assessment in accordance to RECIST 1.1. DCR was assessed in Group 1, 2, 3 and 4 (Phase II) 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 diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
Up to approximately 4 years
Phase Ib: Overall Survival (OS)
OS is defined as the time from first dose of the study treatment to the date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant was not known to have died, survival was censored at the date of last contact. OS was assessed in Phase Ib participants
From date of first dose to death, assessed up to approximately 5 years
Phase II Groups 1, 2, 3 and 4: Overall Survival (OS)
OS is defined as the time from first dose of the study treatment to the date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant was not known to have died, survival was censored at the date of last contact. OS was assessed in Group 1, 2, 3 and 4
From date of first dose to death, assessed up to approximately 4 years
Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Phase Ib: Peak Plasma Concentration (Cmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Phase Ib: Peak Plasma Concentration (Cmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Phase II Group 5: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment.
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 diameters of all target lesions, taking as reference the baseline sum of diameters.
From date of first documented response to the date of first documented disease progression or death, assessed up to approximately 3 years (while on INC280 monotherapy)
Phase II Group 5: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
DCR is defined as the percentage of participants with best overall response of CR, PR, or SD determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment.
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 diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
Up to approximately 3 years (while on INC280 monotherapy)
Phase II Group 5: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment.
Up to approximately 3 years (while on INC280 monotherapy)
Phase II Group 5: Number of Participants With Dose Modifications for INC280 Monotherapy as Well as INC280 in Combination With EGF816 Therapy
Number of participants with dose modifications for INC280 monotherapy as well as INC280 in combination with EGF816 therapy
From start of treatment until end of treatment, up to approximately 3 years
Phase II Group 5: Dose Intensity for INC280 Monotherapy as Well as INC280 in Combination With EGF816 Therapy
Dose intensity is defined as the ratio of total dose received and actual duration for INC280 monotherapy as well as INC280 in combination with EGF816 therapy in Group 5 (Phase II)
From start of treatment until end of treatment, up to approximately 3 years
Melbourne
Victoria
3000
Australia
Novartis Investigative Site
Edmonton
Alberta
T6G 1Z2
Canada
Novartis Investigative Site
Marseille
13885
France
Novartis Investigative Site
Heidelberg
Baden-Wurttemberg
69126
Germany
Novartis Investigative Site
Cologne
North Rhine-Westphalia
50937
Germany
Novartis Investigative Site
Bologna
BO
40138
Italy
Novartis Investigative Site
Modena
MO
41124
Italy
Novartis Investigative Site
Perugia
PG
06129
Italy
Novartis Investigative Site
Oslo
NO 0424
Norway
Novartis Investigative Site
Singapore
119228
Singapore
Novartis Investigative Site
Singapore
168583
Singapore
Novartis Investigative Site
Seoul
Korea
05505
South Korea
Novartis Investigative Site
Barcelona
Catalonia
08035
Spain
Novartis Investigative Site
A Coruña
Galicia
15006
Spain
Novartis Investigative Site
Las Palmas de Gran Canarias
Las Palmas de Gran Canaria
35016
Spain
Novartis Investigative Site
Madrid
28009
Spain
Novartis Investigative Site
Madrid
28041
Spain
Novartis Investigative Site
Taipei
Taiwan ROC
10041
Taiwan
Derived
Jia Y, Juarez J, Li J, Manuia M, Niederst MJ, Tompkins C, Timple N, Vaillancourt MT, Pferdekamper AC, Lockerman EL, Li C, Anderson J, Costa C, Liao D, Murphy E, DiDonato M, Bursulaya B, Lelais G, Barretina J, McNeill M, Epple R, Marsilje TH, Pathan N, Engelman JA, Michellys PY, McNamara P, Harris J, Bender S, Kasibhatla S. EGF816 Exerts Anticancer Effects in Non-Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor. Cancer Res. 2016 Mar 15;76(6):1591-602. doi: 10.1158/0008-5472.CAN-15-2581. Epub 2016 Jan 29.
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
FG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
FG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
FG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
FG005
Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
FG006
Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
FG007
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
FG008
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
FG009
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, acquired MET amplification who have progressed on one prior line of therapy for advanced/metastatic NSCLC disease. Participants started with 400 mg twice daily for INC280 (monotherapy) (fasted or food state) and then had the opportunity to continue with the combination of 400 mg twice daily for INC280 and 100 mg once daily for EGF816 (fasted or food state)
FG0004 subjects
FG0015 subjects
FG0023 subjects
FG00316 subjects
FG0045 subjects
FG00552 subjects
FG0063 subjects
FG00747 subjects
FG00842 subjects
FG0090 subjectsStudy was early terminated prior to initiating enrollment of Phase II- Group 5
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0052 subjects
FG0060 subjects
FG0075 subjects
FG0086 subjects
FG0090 subjects
NOT COMPLETED
FG0004 subjects
FG0015 subjects
FG0023 subjects
FG00315 subjects
FG0045 subjects
FG00550 subjects
FG0063 subjects
FG00742 subjects
FG00836 subjects
FG0090 subjects
Type
Comment
Reasons
Progressive Disease
FG0002 subjects
FG0015 subjects
FG0022 subjects
FG00311 subjects
FG0044 subjects
FG00525 subjects
FG0062 subjects
FG00730 subjects
FG00827 subjects
FG0090 subjects
Adverse Event
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG004
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Study Terminated By Sponsor
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Subject/Guardian Decision
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Post-treatment Follow-up
Type
Comment
Milestone Data
STARTED
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG0040 subjects
FG00513 subjects
FG0060 subjects
FG0075 subjects
FG0083 subjects
FG0090 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG004
Type
Comment
Reasons
Progressive Disease
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
No participants were enrolled in Phase II-Group 5 arm due to early study termination.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
BG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
BG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
BG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
BG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
BG005
Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
BG006
Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
BG007
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
BG008
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
BG009
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, acquired MET amplification who have progressed on one prior line of therapy for advanced/metastatic NSCLC disease. Participants started with 400 mg twice daily for INC280 (monotherapy) (fasted or food state) and then had the opportunity to continue with the combination of 400 mg twice daily for INC280 and 100 mg once daily for EGF816 (fasted or food state)
BG010
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0004
BG0015
BG0023
BG00316
BG0045
BG00552
BG0063
BG00747
BG00842
BG0090
BG010177
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0004
BG0013
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Asian
BG0002
BG0013
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs)
Number of participants with DLTs in the Phase Ib part. A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment with EGF816 in combination with INC280 during the escalation part of the study (Phase Ib)
All participants in Phase Ib part who received at least one dose of INC280 or EGF816, and who either completed a minimum exposure requirement or who had a DLT during the first 28 days of treatment (Cycle 1)
Posted
Count of Participants
Participants
Up to first 28 days of treatment
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0021
OG003
Title
Denominators
Categories
Title
Measurements
OG0001
OG0010
OG0020
OG003
Primary
Phase II Group 1, 2 and 3: Overall Response Rate (ORR) by Investigator's Assessment Per RECIST 1.1
ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) determined by investigator's assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). ORR was assessed in Group 1, 2 and 3 (Phase II part).
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 diameters of all target lesions, taking as reference the baseline sum of diameters.
All participants in Group 1, 2 or 3 (Phase II part) who received at least one dose of either INC280 or EGF816
Posted
Number
95% Confidence Interval
Percentage of participants
Up to approximately 4 years
ID
Title
Description
OG000
Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)
Primary
Phase II Group 4: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Number of participants in Group 4 (Phase II part) with AEs and SAEs. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
All participants in Group 4 (Phase II part) who received at least one dose of INC280 or EGF816
Posted
Count of Participants
Participants
From start of treatment up to 30 days after last dose of study treatment, assessed up to 3.7 years
ID
Title
Description
OG000
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Units
Counts
Participants
Primary
Phase II Group 4: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618
Number of participants with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 in the Group 4 (Phase II part).
All participants in Group 4 (Phase II part) who received at least one dose of INC280 or EGF816
Posted
Count of Participants
Participants
From start of treatment until end of treatment, assessed up to 3.6 years
ID
Title
Description
OG000
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Units
Counts
Participants
OG000
Primary
Phase II Group 4: Dose Intensity
Dose intensity, defined as the ratio of total dose received and actual duration, for participants in Group 4 (Phase II part)
All participants in Group 4 (Phase II part) who received at least one dose of INC280 or EGF816
Posted
Mean
Standard Deviation
milligram/day
From start of treatment until end of treatment, assessed up to 3.6 years
ID
Title
Description
OG000
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Units
Counts
Participants
OG000
Primary
Phase II Group 5: ORR Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) determined by Investigator assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for participants in Group 5 (Phase II part) while on treatment with INC280 monotherapy.
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 diameters of all target lesions, taking as reference the baseline sum of diameters.
Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Posted
Up to approximately 3 years (while on INC280 monotherapy)
ID
Title
Description
OG000
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, acquired MET amplification who have progressed on one prior line of therapy for advanced/metastatic NSCLC disease. Participants started with 400 mg twice daily for INC280 (monotherapy) (fasted or food state) and then had the opportunity to continue with the combination of 400 mg twice daily for INC280 and 100 mg once daily for EGF816 (fasted or food state)
Units
Counts
Secondary
Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618
Number of participants in Phase Ib with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 .
All participants in Phase Ib part who received at least one dose of INC280 or EGF816
Posted
Count of Participants
Participants
From start of treatment until end of treatment, assessed up to approximately 5 years
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Secondary
Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618
Number of participants in Groups 1, 2 and 3 (Phase II part) with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 .
All participants in Group 1, 2 and 3 (Phase II part) who received at least one dose of INC280 or EGF816
Posted
Count of Participants
Participants
From start of treatment until end of treatment, assessed up to approximately 4 years
ID
Title
Description
OG000
Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
Secondary
Phase Ib: Dose Intensity
Dose intensity, defined as the ratio of total dose received and actual duration, in Phase Ib participants
All participants in Phase Ib part who received at least one dose of INC280 or EGF816
Posted
Mean
Standard Deviation
milligram/day
From start of treatment until end of treatment, assessed up to approximately 5 years
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Secondary
Phase II Group 1, 2 and 3: Dose Intensity
Dose intensity, defined as the ratio of total dose received and actual duration, in Group 1, 2 and 3 (Phase II)
All participants in Group 1, 2 and 3 (Phase II part) who received at least one dose of INC280 or EGF816
Posted
Mean
Standard Deviation
milligram/day
From start of treatment until end of treatment, assessed up to approximately 4 years
ID
Title
Description
OG000
Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG002
Secondary
Phase Ib: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment
ORR is defined as percentage of participants with best overall response of PR+CR determined by Investigator's assessment in accordance to RECIST 1.1. ORR was assessed in Phase Ib participants.
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 diameters of all target lesions, taking as reference the baseline sum of diameters.
All participants in Phase Ib part who received at least one dose of INC280 or EGF816
Posted
Number
95% Confidence Interval
Percentage of participants
Up to approximately 5 years
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Secondary
Phase II Group 4: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment
ORR is defined as percentage of participants with best overall response of PR+CR determined by Investigator's assessment in accordance to RECIST 1.1. ORR was assessed in Group 4 (Phase II) 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 diameters of all target lesions, taking as reference the baseline sum of diameters.
All participants in Group 4 (Phase II part) who received at least one dose of INC280 or EGF816
Posted
Number
95% Confidence Interval
Percentage of participants
Up to approximately 4 years
ID
Title
Description
OG000
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Units
Counts
Participants
Secondary
Phase Ib: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment
PFS is defined as time from date of first dose of study treatment to date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1.or death due to any cause. The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, PFS is censored at the date of last adequate tumor assessment. PFS was assessed in Phase Ib participants
All participants in Phase Ib part who received at least one dose of INC280 or EGF816
Posted
Median
95% Confidence Interval
Months
From date of first dose to first documented disease progression or death, assessed up to approximately 5 years
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Secondary
Phase II Groups 1, 2, 3 and 4: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment
PFS is defined as time from date of first dose of study treatment to date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1.or death due to any cause. The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, PFS is censored at the date of last adequate tumor assessment. PFS was assessed in Group 1, 2, 3 and 4 (Phase II)
All participants in Group 1, 2 ,3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816
Posted
Median
95% Confidence Interval
Months
From date of first dose to first documented disease progression or death, assessed up to approximately 4 years
ID
Title
Description
OG000
Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
Secondary
Phase Ib: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment
TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment in accordance to RECIST 1.1. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. TTR was assessed in Phase Ib participants.
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 diameters of all target lesions, taking as reference the baseline sum of diameters.
All participants in Phase Ib part who received at least one dose of INC280 or EGF816
Posted
Median
95% Confidence Interval
Months
From the date of the first dose to the date of first documented response, up to approximately 5 years
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Secondary
Phase II Groups 1, 2, 3 and 4: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment
TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment in accordance to RECIST 1.1. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. TTR was assessed in Group 1, 2, 3 and 4 (Phase II) 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 diameters of all target lesions, taking as reference the baseline sum of diameters.
All participants in Group 1, 2 ,3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816
Posted
Median
95% Confidence Interval
Months
From the date of the first dose to the date of first documented response, up to approximately 4 years
ID
Title
Description
OG000
Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Secondary
Phase Ib: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment
DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1 or death due to underlying cancer. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. DOR was assessed in Phase Ib participants 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 diameters of all target lesions, taking as reference the baseline sum of diameters.
All participants in Phase Ib part who received at least one dose of INC280 or EGF816 and had a documented response (CR or PR)
Posted
Median
95% Confidence Interval
Months
From date of first documented response to first documented disease progression or death, assessed up to approximately 5 years
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Secondary
Phase II Groups 1, 2, 3 and 4: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment
DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1 or death due to underlying cancer. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. DOR was assessed in Group 1, 2, 3 and 4 (Phase II) 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 diameters of all target lesions, taking as reference the baseline sum of diameters.
All participants in Group 1, 2 ,3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816 and had a documented response (CR or PR)
Posted
Median
95% Confidence Interval
Months
From date of first documented response to first documented disease progression or deaths, assessed up to approximately 4 years
ID
Title
Description
OG000
Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
Secondary
Phase Ib: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment
DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease (SD) determined by Investigator assessment in accordance to RECIST 1.1. DCR was assessed in Phase Ib participants 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 diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
All participants in Phase Ib part who received at least one dose of INC280 or EGF816
Posted
Number
95% Confidence Interval
Percentage of participants
Up to approximately 5 years
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Secondary
Phase II Group 1, 2 3 and 4: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment
DCR is defined as the percentage of participants with best overall response of CR, PR, or SD determined by Investigator assessment in accordance to RECIST 1.1. DCR was assessed in Group 1, 2, 3 and 4 (Phase II) 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 diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
All participants in Group 1, 2 ,3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816
Posted
Number
95% Confidence Interval
Percentage of participants
Up to approximately 4 years
ID
Title
Description
OG000
Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)
Secondary
Phase Ib: Overall Survival (OS)
OS is defined as the time from first dose of the study treatment to the date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant was not known to have died, survival was censored at the date of last contact. OS was assessed in Phase Ib participants
All participants in Phase Ib part who received at least one dose of INC280 or EGF816
Posted
Median
95% Confidence Interval
Months
From date of first dose to death, assessed up to approximately 5 years
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Secondary
Phase II Groups 1, 2, 3 and 4: Overall Survival (OS)
OS is defined as the time from first dose of the study treatment to the date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant was not known to have died, survival was censored at the date of last contact. OS was assessed in Group 1, 2, 3 and 4
All participants in Group 1, 2 ,3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816
Posted
Median
95% Confidence Interval
Months
From date of first dose to death, assessed up to approximately 4 years
ID
Title
Description
OG000
Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
Secondary
Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280.
Posted
Mean
Standard Deviation
hours*nanogram/mililiter (hr*ng/mL)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Secondary
Phase Ib: Peak Plasma Concentration (Cmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280.
Posted
Mean
Standard Deviation
nanogram/mililiter (ng/mL)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Secondary
Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280.
Posted
Median
Full Range
Hours
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Secondary
Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280
Posted
Mean
Standard Deviation
hours*nanogram/mililiter (hr*ng/mL)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Secondary
Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280
Posted
Mean
Standard Deviation
nanogram/mililiter (ng/mL)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Secondary
Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280
Posted
Median
Full Range
Hours
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Secondary
Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
Posted
Mean
Standard Deviation
hours*nanogram/mililiter (hr*ng/mL)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Secondary
Phase Ib: Peak Plasma Concentration (Cmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
Posted
Mean
Standard Deviation
nanogram/mililiter (ng/mL)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Secondary
Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
Posted
Median
Full Range
Hours (hr)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Secondary
Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
Posted
Mean
Standard Deviation
hours*nanogram/mililiter (hr*ng/mL)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Secondary
Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
Posted
Mean
Standard Deviation
nanogram/mililiter (ng/mL)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Secondary
Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
Posted
Median
Full Range
Hours (hr)
Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
ID
Title
Description
OG000
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG001
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Secondary
Phase II Group 5: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment.
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 diameters of all target lesions, taking as reference the baseline sum of diameters.
Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Posted
From date of first documented response to the date of first documented disease progression or death, assessed up to approximately 3 years (while on INC280 monotherapy)
ID
Title
Description
OG000
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, acquired MET amplification who have progressed on one prior line of therapy for advanced/metastatic NSCLC disease. Participants started with 400 mg twice daily for INC280 (monotherapy) (fasted or food state) and then had the opportunity to continue with the combination of 400 mg twice daily for INC280 and 100 mg once daily for EGF816 (fasted or food state)
Secondary
Phase II Group 5: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
DCR is defined as the percentage of participants with best overall response of CR, PR, or SD determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment.
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 diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Posted
Up to approximately 3 years (while on INC280 monotherapy)
ID
Title
Description
OG000
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, acquired MET amplification who have progressed on one prior line of therapy for advanced/metastatic NSCLC disease. Participants started with 400 mg twice daily for INC280 (monotherapy) (fasted or food state) and then had the opportunity to continue with the combination of 400 mg twice daily for INC280 and 100 mg once daily for EGF816 (fasted or food state)
Secondary
Phase II Group 5: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment.
Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Posted
Up to approximately 3 years (while on INC280 monotherapy)
ID
Title
Description
OG000
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, acquired MET amplification who have progressed on one prior line of therapy for advanced/metastatic NSCLC disease. Participants started with 400 mg twice daily for INC280 (monotherapy) (fasted or food state) and then had the opportunity to continue with the combination of 400 mg twice daily for INC280 and 100 mg once daily for EGF816 (fasted or food state)
Units
Counts
Participants
OG000
Secondary
Phase II Group 5: Number of Participants With Dose Modifications for INC280 Monotherapy as Well as INC280 in Combination With EGF816 Therapy
Number of participants with dose modifications for INC280 monotherapy as well as INC280 in combination with EGF816 therapy
Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Posted
From start of treatment until end of treatment, up to approximately 3 years
ID
Title
Description
OG000
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, acquired MET amplification who have progressed on one prior line of therapy for advanced/metastatic NSCLC disease. Participants started with 400 mg twice daily for INC280 (monotherapy) (fasted or food state) and then had the opportunity to continue with the combination of 400 mg twice daily for INC280 and 100 mg once daily for EGF816 (fasted or food state)
Units
Counts
Participants
OG000
Secondary
Phase II Group 5: Dose Intensity for INC280 Monotherapy as Well as INC280 in Combination With EGF816 Therapy
Dose intensity is defined as the ratio of total dose received and actual duration for INC280 monotherapy as well as INC280 in combination with EGF816 therapy in Group 5 (Phase II)
Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Posted
From start of treatment until end of treatment, up to approximately 3 years
ID
Title
Description
OG000
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, acquired MET amplification who have progressed on one prior line of therapy for advanced/metastatic NSCLC disease. Participants started with 400 mg twice daily for INC280 (monotherapy) (fasted or food state) and then had the opportunity to continue with the combination of 400 mg twice daily for INC280 and 100 mg once daily for EGF816 (fasted or food state)
Units
Counts
Participants
OG000
Post-Hoc
All Collected Deaths
On-treatment deaths were collected from first dose of study medication to 30 days after the last dose of study medication.
Post-treatment survival follow-up deaths were collected after 30 days post-treatment.
All deaths refer to the sum of on-treatment and post-treatment deaths
All participants in Phase Ib part and Group 1, 2, 3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816. Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Posted
Count of Participants
Participants
On-treatment: up to approximately 5 years (Phase Ib) and 4 years (Phase II). Post-treatment survival follow-up: Up to approximately 5 years (Phase Ib) and 4 years (Phase II).
ID
Title
Description
OG000
Phase IB Part- INC280 200mg BID/ EGF816 50mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG001
Phase IB Part- INC280 200mg BID/ EGF816 100mg QD
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Time Frame
Adverse events were collected from first dose of study treatment to 30 days after last dose of study treatment, up to approx. 5 years (Phase Ib) and 4 years (Phase II). Deaths were collected in the post treatment survival follow up from 31 days after last dose of study medication until the end of the study, up to approx. 5 years (Phase Ib) and 4 years (Phase II).These are not considered AEs
Description
Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events. The total number at risk in the post treatment survival includes patients that entered the post treatment survival follow-up period.
Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Deaths collected in the post- treatment survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period
25
37
0
0
0
0
EG016
Phase II-EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic (On-treatment)
AEs collected during on-treatment period (up to 30 days post-treatment)
1
42
26
42
42
42
EG017
Phase II-EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic (Post-treatment FU)
Deaths collected in the post- treatment survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period
22
33
0
0
0
0
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Disseminated intravascular coagulation
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG0030 at risk
EG004
Leukopenia
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Cardiac arrest
Cardiac disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Cardio-respiratory arrest
Cardiac disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Myocardial ischaemia
Cardiac disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypoacusis
Ear and labyrinth disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Visual impairment
Eye disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Gastric ulcer
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hiatus hernia
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Inguinal hernia
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Asthenia
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Fatigue
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
General physical health deterioration
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Influenza like illness
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Oedema
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pyrexia
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hepatic failure
Hepatobiliary disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Anaphylactic shock
Immune system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Cellulitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Empyema
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Enterocolitis infectious
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Erysipelas
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Herpes zoster meningitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Influenza
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Meningitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Meningitis aseptic
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Necrotising fasciitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pleural infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pneumonia aspiration
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pneumonia chlamydial
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Sepsis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Soft tissue infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Urosepsis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Amylase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Ejection fraction decreased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Weight decreased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Electrolyte imbalance
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Osteonecrosis
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Invasive ductal breast carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Malignant pleural effusion
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Tumour associated fever
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Aphasia
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Brain oedema
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Cerebral ischaemia
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Dysarthria
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Epilepsy
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Headache
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hydrocephalus
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypertensive hydrocephalus
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Loss of consciousness
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Neurological decompensation
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Seizure
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Speech disorder
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Spinal cord compression
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Tremor
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Wernicke's encephalopathy
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Apathy
Psychiatric disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypersensitivity pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Dermatitis allergic
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Drug eruption
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Erythema multiforme
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Purpura
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Embolism
Vascular disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypertensive crisis
Vascular disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypotension
Vascular disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG0030 at risk
EG0042 affected3 at risk
EG0050 at risk
EG0062 affected16 at risk
EG0070 at risk
EG0081 affected5 at risk
EG0090 at risk
EG0109 affected52 at risk
EG0110 at risk
EG0121 affected3 at risk
EG0130 at risk
EG01411 affected47 at risk
EG0150 at risk
EG0164 affected42 at risk
EG0170 at risk
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0022 affected5 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Angina pectoris
Cardiac disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Deafness
Ear and labyrinth disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Deafness transitory
Ear and labyrinth disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypoacusis
Ear and labyrinth disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hyperthyroidism
Endocrine disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Eye pruritus
Eye disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Eye swelling
Eye disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Eyelid oedema
Eye disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Vision blurred
Eye disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Vitreous floaters
Eye disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Lip blister
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Lip dry
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0002 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Odynophagia
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Asthenia
General disorders
MedDRA (25.0)
Systematic Assessment
EG0002 affected4 at risk
EG0010 at risk
EG0022 affected5 at risk
EG003
Chest pain
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Chills
General disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Face oedema
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Fatigue
General disorders
MedDRA (25.0)
Systematic Assessment
EG0002 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Gait disturbance
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Influenza like illness
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Oedema peripheral
General disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Pain
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Peripheral swelling
General disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pyrexia
General disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Hypertransaminasaemia
Hepatobiliary disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Anaphylactoid reaction
Immune system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Cellulitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0022 affected5 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Cystitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Folliculitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Paronychia
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Rhinitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Sinobronchitis
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Skin infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Tooth infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Viral infection
Infections and infestations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Traumatic haematoma
Injury, poisoning and procedural complications
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0002 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Amylase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0002 affected4 at risk
EG0010 at risk
EG0022 affected5 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Blood albumin decreased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Blood creatine increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0002 affected4 at risk
EG0010 at risk
EG0022 affected5 at risk
EG003
Blood glucose increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Blood potassium increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Blood triglycerides increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Blood urea increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Blood uric acid increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
C-reactive protein increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Haemoglobin decreased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Lipase increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Protein total decreased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Weight decreased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Weight increased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
White blood cell count decreased
Investigations
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0002 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hyperlipasaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypophagia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypoproteinaemia
Metabolism and nutrition disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0002 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Joint stiffness
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Tendon pain
Musculoskeletal and connective tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Amnesia
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Dysaesthesia
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Epilepsy
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Headache
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Lethargy
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Post herpetic neuralgia
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Seizure
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Syncope
Nervous system disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Depression
Psychiatric disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Sleep disorder
Psychiatric disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Chronic kidney disease
Renal and urinary disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypertonic bladder
Renal and urinary disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pelvic pain
Reproductive system and breast disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Perineal pain
Reproductive system and breast disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Prostatomegaly
Reproductive system and breast disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Vulvovaginal pruritus
Reproductive system and breast disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0022 affected5 at risk
EG003
Dry throat
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Nasal discomfort
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Nasal dryness
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0002 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Throat irritation
Respiratory, thoracic and mediastinal disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Dermatitis acneiform
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Ingrowing nail
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Nail discolouration
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Palmar-plantar erythrodysaesthesia syndrome
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0021 affected5 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0022 affected5 at risk
EG003
Rash papular
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Rash pruritic
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Skin hyperpigmentation
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hot flush
Vascular disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Hypotension
Vascular disorders
MedDRA (25.0)
Systematic Assessment
EG0001 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Pallor
Vascular disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Thrombosis
Vascular disorders
MedDRA (25.0)
Systematic Assessment
EG0000 affected4 at risk
EG0010 at risk
EG0020 affected5 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG002
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
Units
Counts
Participants
OG00052
OG0013
OG00247
Title
Denominators
Categories
Title
Measurements
OG00028.8(17.1 to 43.10)
OG00133.3(0.8 to 90.6)
OG00261.7(46.4 to 75.5)
OG00042
Title
Denominators
Categories
AEs
Title
Measurements
OG00042
SAEs
Title
Measurements
OG00026
42
Title
Denominators
Categories
Dose Reduction of INC280
Title
Measurements
OG00030
Dose Interruption of INC280
Title
Measurements
OG00031
Dose Reduction of EGF816
Title
Measurements
OG00012
Dose Interruption of EGF816
Title
Measurements
OG00035
42
Title
Denominators
Categories
INC280
Title
Measurements
OG000666.2± 148.97
EGF816
Title
Measurements
OG00087.4± 14.82
Participants
OG0000
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0023
OG00316
OG0045
Title
Denominators
Categories
Dose Reduction of INC280
Title
Measurements
OG0002
OG0014
OG0022
OG00310
OG0045
Dose Interruption of INC280
Title
Measurements
OG0002
OG0012
OG0022
OG003
Dose Reduction of EGF816
Title
Measurements
OG0002
OG0011
OG0021
OG003
Dose Interruption of EGF816
Title
Measurements
OG0002
OG0012
OG0022
OG003
OG002
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
Units
Counts
Participants
OG00052
OG0013
OG00247
Title
Denominators
Categories
Dose Reduction of INC280
Title
Measurements
OG00033
OG0013
OG00234
Dose Interruption of INC280
Title
Measurements
OG00031
OG0013
OG00239
Dose Reduction of EGF816
Title
Measurements
OG00017
OG0012
OG00223
Dose Interruption of EGF816
Title
Measurements
OG00034
OG0013
OG00240
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0023
OG00316
OG0045
Title
Denominators
Categories
INC280
Title
Measurements
OG000319.1± 101.09
OG001356.9± 71.14
OG002596.3± 200.24
OG003658.2± 158.18
OG004463.4± 212.52
EGF816
Title
Measurements
OG00040.0± 12.60
OG00189.6± 17.93
OG00260.0± 13.36
OG003
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
Units
Counts
Participants
OG00052
OG0013
OG00247
Title
Denominators
Categories
INC280
Title
Measurements
OG000662.9± 160.73
OG001562.9± 38.36
OG002634.7± 172.33
EGF816
Title
Measurements
OG00085.2± 18.21
OG00176.3± 15.31
OG00284.8± 15.53
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0023
OG00316
OG0045
Title
Denominators
Categories
Title
Measurements
OG0000(0.0 to 60.2)
OG00140.0(5.3 to 85.3)
OG00233.3(0.8 to 90.6)
OG00350.0(24.7 to 75.3)
OG00460.0(14.7 to 94.7)
OG000
42
Title
Denominators
Categories
Title
Measurements
OG00042.9(27.7 to 59.0)
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0023
OG00316
OG0045
Title
Denominators
Categories
Title
Measurements
OG0005.6(3.5 to NA)NA: Not estimable due to insufficient number of participants with events.
OG0017.4(1.6 to NA)NA: Not estimable due to insufficient number of participants with events.
OG0023.5(0.8 to NA)NA: Not estimable due to insufficient number of participants with events.
OG0035.7(1.9 to 42.1)
OG00414.5(7.3 to NA)NA: Not estimable due to insufficient number of participants with events.
OG002
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG003
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Units
Counts
Participants
OG00052
OG0013
OG00247
OG00342
Title
Denominators
Categories
Title
Measurements
OG0005.6(3.7 to 7.4)
OG0013.8(3.7 to NA)NA: Not estimable due to insufficient number of participants with events.
OG00210.1(7.6 to 13.8)
OG00310.9(5.6 to 19.2)
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0023
OG00316
OG0045
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)NA: Not estimable due to insufficient number of participants with events.
OG001NA(1.8 to NA)NA: Not estimable due to insufficient number of participants with events.
OG002NA(1.7 to NA)NA: Not estimable due to insufficient number of participants with events.
OG0033.5(1.6 to NA)NA: Not estimable due to insufficient number of participants with events.
OG0044.5(1.9 to NA)NA: Not estimable due to insufficient number of participants with events.
Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG002
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG003
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Units
Counts
Participants
OG00052
OG0013
OG00247
OG00342
Title
Denominators
Categories
Title
Measurements
OG000NA(5.4 to NA)NA: Not estimable due to insufficient number of participants with events.
OG001NA(1.8 to NA)NA: Not estimable due to insufficient number of participants with events.
OG0021.9(1.8 to 5.9)
OG003NA(3.6 to NA)NA: Not estimable due to insufficient number of participants with events.
Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0000
OG0012
OG0021
OG0038
OG0043
Title
Denominators
Categories
Title
Measurements
OG0018.8(5.6 to NA)NA: Not estimable due to insufficient number of participants with events.
OG00214.8(NA to NA)NA: Not estimable due to insufficient number of participants with events.
OG00325.3(3.6 to 47.9)
OG0048.0(5.4 to NA)NA: Not estimable due to insufficient number of participants with events.
OG001
Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG002
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG003
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Units
Counts
Participants
OG00015
OG0011
OG00229
OG00318
Title
Denominators
Categories
Title
Measurements
OG0006.5(3.7 to 10.8)
OG00112.0(NA to NA)NA: Not estimable due to insufficient number of participants with events.
OG00211.6(6.6 to 17.5)
OG00314.5(9.2 to NA)NA: Not estimable due to insufficient number of participants with events.
OG002
Phase IB Part- INC280 400mg BID/ EGF816 75mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0023
OG00316
OG0045
Title
Denominators
Categories
Title
Measurements
OG000100(39.8 to 100)
OG00160.0(14.7 to 94.7)
OG00233.3(0.8 to 90.6)
OG00362.5(35.4 to 84.8)
OG00480.0(28.4 to 99.5)
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG002
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG003
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Units
Counts
Participants
OG00052
OG0013
OG00247
OG00342
Title
Denominators
Categories
Title
Measurements
OG00059.6(45.1 to 73.0)
OG001100(29.2 to 100)
OG00293.6(82.5 to 98.7)
OG00381.0(65.9 to 91.4)
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0023
OG00316
OG0045
Title
Denominators
Categories
Title
Measurements
OG00010.1(8.1 to NA)NA: Not estimable due to insufficient number of participants with events.
OG00156.5(6.5 to NA)NA: Not estimable due to insufficient number of participants with events.
OG0027.0(1.1 to NA)NA: Not estimable due to insufficient number of participants with events.
OG00317.2(5.7 to 58.7)
OG00431.5(16.6 to NA)NA: Not estimable due to insufficient number of participants with events.
OG002
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG003
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
Units
Counts
Participants
OG00052
OG0013
OG00247
OG00342
Title
Denominators
Categories
Title
Measurements
OG00018.8(14.9 to 26.0)
OG0015.6(3.7 to NA)NA: Not estimable due to insufficient number of participants with events.
OG00225.6(18.8 to 33.0)
OG00328.9(20.5 to NA)NA: Not estimable due to insufficient number of participants with events.
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0021
OG00312
OG0043
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0021
ParticipantsOG00312
ParticipantsOG0043
Title
Measurements
OG00012300± 4710
OG00110500± 4320
OG00238300
OG003
Cycle 1 Day 15
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0021
ParticipantsOG00311
Cycle 2 Day 1
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0020
ParticipantsOG0039
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0021
OG00312
OG0043
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0004
ParticipantsOG0015
ParticipantsOG0021
ParticipantsOG00312
ParticipantsOG0043
Title
Measurements
OG0003630± 588
OG0012530± 1080
OG0028000
OG003
Cycle 1 Day 15
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0021
ParticipantsOG00311
Cycle 2 Day 1
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0020
ParticipantsOG00310
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0021
OG00312
OG0043
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0004
ParticipantsOG0015
ParticipantsOG0021
ParticipantsOG00312
ParticipantsOG0043
Title
Measurements
OG0001.07(1.00 to 2.00)
OG0012.00(1.00 to 4.00)
OG0022.00(2.00 to 2.00)
OG003
Cycle 1 Day 15
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0021
ParticipantsOG00311
Cycle 2 Day 1
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0020
ParticipantsOG00310
Units
Counts
Participants
OG0009
OG00115
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0008
ParticipantsOG00112
Title
Measurements
OG00022000± 8000
OG00116900± 7360
Cycle 2 Day 1
ParticipantsOG0008
ParticipantsOG00115
Title
Measurements
OG00019700± 11200
OG001
Units
Counts
Participants
OG0009
OG00115
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0008
ParticipantsOG00112
Title
Measurements
OG0004770± 1460
OG0013420± 1550
Cycle 2 Day 1
ParticipantsOG0008
ParticipantsOG00115
Title
Measurements
OG0004360± 2060
OG001
Units
Counts
Participants
OG0009
OG00115
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0008
ParticipantsOG00112
Title
Measurements
OG0001.99(1.00 to 4.00)
OG0012.08(1.85 to 8.00)
Cycle 2 Day 1
ParticipantsOG0008
ParticipantsOG00115
Title
Measurements
OG0001.47(1.00 to 7.08)
OG001
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0023
OG00313
OG0043
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0022
ParticipantsOG00311
ParticipantsOG0042
Title
Measurements
OG0003920± 1450
OG0015850± 4380
OG0024010± 534
OG003
Cycle 1 Day 15
ParticipantsOG0004
ParticipantsOG0015
ParticipantsOG0022
ParticipantsOG00312
Cycle 2 Day 1
ParticipantsOG0003
ParticipantsOG0014
ParticipantsOG0020
ParticipantsOG00311
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0023
OG00313
OG0043
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0004
ParticipantsOG0015
ParticipantsOG0022
ParticipantsOG00313
ParticipantsOG0043
Title
Measurements
OG000258± 104
OG001465± 323
OG002302± 8.49
OG003
Cycle 1 Day 15
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0023
ParticipantsOG00312
Cycle 2 Day 1
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0020
ParticipantsOG00311
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
Units
Counts
Participants
OG0004
OG0015
OG0023
OG00313
OG0043
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0004
ParticipantsOG0015
ParticipantsOG0022
ParticipantsOG00313
ParticipantsOG0043
Title
Measurements
OG0003.03(1.08 to 4.02)
OG0013.90(2.00 to 4.00)
OG0023.00(2.00 to 4.00)
OG003
Cycle 1 Day 15
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0023
ParticipantsOG00312
Cycle 2 Day 1
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0020
ParticipantsOG00311
Units
Counts
Participants
OG0007
OG00115
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0006
ParticipantsOG00112
Title
Measurements
OG0006390± 2460
OG0013420± 1700
Cycle 2 Day 1
ParticipantsOG0005
ParticipantsOG00115
Title
Measurements
OG00011100± 2000
OG001
Units
Counts
Participants
OG0007
OG00115
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0006
ParticipantsOG00112
Title
Measurements
OG000448± 184
OG001239± 107
Cycle 2 Day 1
ParticipantsOG0006
ParticipantsOG00115
Title
Measurements
OG000658± 117
OG001
Units
Counts
Participants
OG0007
OG00115
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0006
ParticipantsOG00112
Title
Measurements
OG0004.00(1.12 to 8.00)
OG0014.00(1.85 to 8.00)
Cycle 2 Day 1
ParticipantsOG0006
ParticipantsOG00115
Title
Measurements
OG0004.00(2.00 to 4.13)
OG001
Units
Counts
Participants
OG0000
Units
Counts
Participants
OG0000
0
0
0
Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG003
Phase IB Part- INC280 400mg BID/ EGF816 100mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG004
Phase IB Part- INC280 400mg BID/ EGF816 150mg QD
Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment
OG005
Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG006
Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)
NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG007
Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state
OG008
Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)
NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state.
OG009
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant)
NSCLC participants with previously documented EGFR activating mutation, T790M negative, acquired MET amplification who have progressed on one prior line of therapy for advanced/metastatic NSCLC disease. Participants started with 400 mg twice daily for INC280 (monotherapy) (fasted or food state) and then had the opportunity to continue with the combination of 400 mg twice daily for INC280 and 100 mg once daily for EGF816 (fasted or food state)