Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT02323126
Collaborator
(none)
64
13
3
71.9
4.9
0.1
Study Details
Study Description
Brief Summary
To determine the efficacy and safety of nivolumab in combination with EGF816 and of nivolumab in combination with INC280 in previously treated NSCLC patients
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This was a phase II, multi-center, open-label study in patients with advanced non-small cell lung cancer (NSCLC). Patients were allocated based on their epidermal growth factor receptor (EGFR) status to one of the 2 groups: Group 1 - EGFR T790M NSCLC treated with EGF816 150 mg once daily (QD) + nivolumab 3 mg/kg every 2 weeks (Q2W), and Group 2 - EGFR wild type (wt) NSCLC treated with INC280 400 mg twice daily (BID) + nivolumab 3 mg/kg Q2W. Patients in Group 2 were subdivided into 2 subgroups based on c-Mesenchymal-epithelial transition (cMet) status: Subgroup A - high cMet (referred to as Group 2A) and Subgroup B- low cMet (referred to as Group 2B).
Patients could continue study treatment until patients experienced unacceptable toxicity that precluded any further treatment, disease progression and/or treatment was discontinued at the discretion of the investigator or withdrawal of consent, or the patient was transferred to a Novartis roll-over study or an alternative treatment option that could continue to provide study treatments. Following the approval of a protocol amendment, the maximum treatment duration for nivolumab could not exceed 2 years and patients who had received nivolumab beyond 2 years were discontinued from nivolumab treatment and continued on EGF816 or INC280 alone.
The primary objective of the trial was to estimate the clinical activity of nivolumab in combination with EGF816 or INC280.
Study Design
Study Type:
Interventional
Actual Enrollment
:
64 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Multicenter, Open-label Study of EGF816 in Combination With Nivolumab in Adult Patients With EGFR Mutated Non-small Cell Lung Cancer and of INC280 in Combination With Nivolumab in Adult Patients With cMet Positive Non-small Cell Lung Cancer
Actual Study Start Date
:
Feb 9, 2015
Actual Primary Completion Date
:
Sep 23, 2019
Actual Study Completion Date
:
Feb 5, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Nivolumab and EGF816 Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W |
Drug: EGF816
EGF816 150 mg once daily (QD) administered orally as a capsule
Drug: Nivolumab
Nivolumab 3 mg/kg every 2 weeks (Q2W) administered by intravenous infusion
|
| Experimental: Nivolumab and INC280, high cMet Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W |
Drug: INC280
INC280 400 mg twice daily (BID) administered orally as a tablet
Drug: Nivolumab
Nivolumab 3 mg/kg every 2 weeks (Q2W) administered by intravenous infusion
|
| Experimental: Nivolumab and INC280, low cMet Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
Drug: INC280
INC280 400 mg twice daily (BID) administered orally as a tablet
Drug: Nivolumab
Nivolumab 3 mg/kg every 2 weeks (Q2W) administered by intravenous infusion
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival (PFS) Rate at 6 Months Per RECIST v1.1 [6 months]
PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PFS was modeled using a Weibull distribution and the PFS rate at 6 months was estimated from the posterior distribution.
Secondary Outcome Measures
- Overall Response Rate (ORR) Per RECIST v1.1 [From start of treatment until end of treatment, assessed up to 4.7 years]
Tumor response was based on local investigator assessment as per RECIST v1.1. ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). For RECIST v1.1, 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 diameter of all target lesions, taking as reference the baseline sum of diameters.
- Disease Control Rate (DCR) Per RECIST v1.1 [From start of treatment until end of treatment, assessed up to 4.7 years]
Tumor response was based on local investigator assessment as per RECIST v1.1. DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD). For RECIST v1.1, 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.
- Median Progression-Free Survival (PFS) Per RECIST v1.1 [From start of treatment to first documented progression or death, assessed up to 5 years]
PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. The median PFS was estimated using the Kaplan-Meier method. Tumor response was based on local investigator assessment as per RECIST v1.1
- Progression-Free Survival (PFS) Rate at 3 Months Per RECIST v1.1 [3 months]
PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The PFS rate at 3 months was estimated using the Kaplan-Meier method.
- Overall Survival (OS) at 1 Year [1 year]
OS represents the percentage of participants who are alive after the start of study treatment. OS at 1 year was estimated using the Kaplan-Meier method.
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years]
Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. AE grades were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
- Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab [From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years]
Number of participants with at least one dose reduction of EGF816, INC280 or nivolumab and number of participants with at least one dose interruption of EGF816, INC280 or nivolumab. Dose reduction was not allowed for nivolumab in this study.
- Dose Intensity of EGF816 and INC280 [From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years]
Dose intensity (mg/day) of EGF816 and INC280 was calculated as actual cumulative dose in milligrams divided by duration of exposure in days.
- Dose Intensity of Nivolumab [From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years]
Dose intensity (mg/kg biweekly) of nivolumab was calculated as actual cumulative dose in mg/kg divided by duration of exposure in days and then multiplied by 14 days (2 weeks).
- Maximum Observed Plasma Concentration (Cmax) of EGF816 [pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.]
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
- Time to Reach Maximum Plasma Concentration (Tmax) of EGF816 [pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.]
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose.
- Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of EGF816 [pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.]
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
- Minimum Observed Plasma Concentration (Cmin) of EGF816 [pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.]
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Cmin is defined as the minimum observed plasma concentration following a dose.
- Maximum Observed Plasma Concentration (Cmax) of INC280 [pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.]
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
- Time to Reach Maximum Plasma Concentration (Tmax) of INC280 [pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.]
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
- Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of INC280 [pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.]
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
- Minimum Observed Plasma Concentration (Cmin) of INC280 [pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.]
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Cmin is defined as the minimum observed plasma concentration following a dose.
- Pre-dose Serum Concentration of Nivolumab [pre-dose on Cycle 1 Day 1 (groups 2A and 2B only) and pre-dose on Cycle 1 Day 15 and Cycle 2 Day 1 (all groups). The duration of one cycle was 28 days.]
Nivolumab serum concentrations were assessed in samples taken at pre-dose. Pre-dose samples were collected before the next dose administration.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Written informed consent must be obtained prior to any screening procedures
-
Presence of at least one measurable lesion according to RECIST v.1.1
-
ECOG performance status ≤ 2
-
Patients with histologically documented locally advanced, recurrent and/or metastatic NSCLC
-
Tumor tissue for determination and/or confirmation of genetic pre-requisites (i.e. EGFR T790M positivity post progression on EGFR TKI for Group 1; cMet status for Group
- must be provided for analysis
Group 1 patients:
-
Patients with EGFR T790M NSCLC (adenocarcinoma)
-
Documented progression of disease according to RECIST v1.1 following primary standard of care (e.g. erlotinib, gefitinib)
Group 2 patients:
-
Patients with EGFR wild-type NSCLC
-
Documented progression of disease according to RECIST v1.1 following standard of care (e.g. platinum doublet).
Exclusion Criteria:
-
Patients who have received more than one prior line of EGFR TKI therapy1 (applies only to Group 1)
-
Previous treatment with a c-MET inhibitor or HGF-targeting therapy (applies only to Group 2)
-
Patients with brain metastases. However, if radiation therapy and/or surgery has been completed and serial evaluation by CT (with contrast enhancement) or MRI over a minimum of one month demonstrates the disease to be stable and if the patient remains asymptomatic without the need for treatment with steroids
-
Patients who require emergent use of systemic steroids, chronic use of prednisone (greater than 10mg or an equivalent steroid dose daily) or emergent surgery and/or radiotherapy.
-
History of allergy or hypersensitivity to nivolumab components
-
Patients with any known or suspected, current or past history of, autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
-
Patients with a condition requiring chronic systemic treatment with either corticosteroids(> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of treatment start. Inhaled or topical steroids, and adrenal replacement steroid doses> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
-
Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
-
Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
-
Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
-
Patients who have been treated with prior PD-1 and PD-L1 agents
-
Patients who previously received agents targeting c-MET and/or EGFR T790M Note: Previous treatment with afatinib may be allowable after discussions between Novartis and Investigator.
-
Patients with the following laboratory abnormalities:
-
Absolute Neutrophil Count (ANC) <1.5 x 109/L
-
Hemoglobin (Hgb) <9 g/dL
-
Platelets <100 x 109/L
-
Total bilirubin >1.5 x upper limit of normal (ULN). For patients with Gilbert's syndrome total bilirubin >2.5 x upper limit of normal (ULN)
-
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN
-
Serum creatinine >1.5 x ULN and/or measured or calculated creatinine clearance <75% LLN
-
For patients being screened for Group 2, asymptomatic serum amylase > CTCAE Grade 2 (1.5-2.0 x ULN). Patients with Grade 1 or Grade 2 serum amylase at the beginning of the study must be confirmed to have no signs or symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging findings of pancreas, etc.)
-
For patients being screened for Group 2: Serum lipase > ULN
-
Female patients who are either pregnant or nursing.
-
Women of child bearing potential who refuse or are not able to use a highly effective method of contraception as defined in the study protocol.
-
Sexually active males unless they use a condom during intercourse while taking drug and for 31 weeks after the last dose of study treatment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Texas MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2) | Houston | Texas | United States | 77030 |
| 2 | Novartis Investigative Site | Camperdown | New South Wales | Australia | 2050 |
| 3 | Novartis Investigative Site | Chermside | Queensland | Australia | 4032 |
| 4 | Novartis Investigative Site | La Tronche | France | 38700 | |
| 5 | Novartis Investigative Site | Koeln | Nordrhein-Westfalen | Germany | 50937 |
| 6 | Novartis Investigative Site | Perugia | PG | Italy | 06129 |
| 7 | Novartis Investigative Site | Aviano | PN | Italy | 33081 |
| 8 | Novartis Investigative Site | Singapore | Singapore | 169610 | |
| 9 | Novartis Investigative Site | Malaga | Andalucia | Spain | 29010 |
| 10 | Novartis Investigative Site | Barcelona | Catalunya | Spain | 08035 |
| 11 | Novartis Investigative Site | Alicante | Comunidad Valenciana | Spain | 03010 |
| 12 | Novartis Investigative Site | Madrid | Spain | 28040 | |
| 13 | Novartis Investigative Site | Chur | Switzerland | 7000 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02323126
Other Study ID Numbers:
- CEGF816X2201C
- 2014-003731-20
First Posted:
Dec 23, 2014
Last Update Posted:
Feb 28, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in 13 investigative sites in 8 countries. |
|---|---|
| Pre-assignment Detail | All patients were required to sign the molecular pre-screening consent to allow for the collection and submission of tumor tissue for determination and/or confirmation of protocol specific pre-requisite genetic alterations. After the molecular pre-screening, the screening period began once patients had signed the study informed consent. Screening evaluations were performed within 28 days prior to the first dose of study medication. After screening, the treatment period started on Cycle 1 Day 1. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Period Title: Overall Study | |||
| STARTED | 18 | 16 | 30 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 18 | 16 | 30 |
Baseline Characteristics
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet | Total |
|---|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W | Total of all reporting groups |
| Overall Participants | 18 | 16 | 30 | 64 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
62.6
(8.77)
|
63.8
(13.05)
|
64.9
(8.45)
|
64.0
(9.75)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
12
66.7%
|
8
50%
|
15
50%
|
35
54.7%
|
| Male |
6
33.3%
|
8
50%
|
15
50%
|
29
45.3%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Asian |
4
22.2%
|
1
6.3%
|
2
6.7%
|
7
10.9%
|
| Caucasian |
14
77.8%
|
14
87.5%
|
26
86.7%
|
54
84.4%
|
| Other |
0
0%
|
0
0%
|
1
3.3%
|
1
1.6%
|
| Unknown |
0
0%
|
1
6.3%
|
1
3.3%
|
2
3.1%
|
Outcome Measures
| Title | Progression-Free Survival (PFS) Rate at 6 Months Per RECIST v1.1 |
|---|---|
| Description | PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PFS was modeled using a Weibull distribution and the PFS rate at 6 months was estimated from the posterior distribution. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had received at least 1 dose of INC280, EGF816 or nivolumab. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 18 | 16 | 30 |
| Number (95% Confidence Interval) [percentage of participants] |
63.4
352.2%
|
68.9
430.6%
|
50.9
169.7%
|
| Title | Overall Response Rate (ORR) Per RECIST v1.1 |
|---|---|
| Description | Tumor response was based on local investigator assessment as per RECIST v1.1. ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). For RECIST v1.1, 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 diameter of all target lesions, taking as reference the baseline sum of diameters. |
| Time Frame | From start of treatment until end of treatment, assessed up to 4.7 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had received at least 1 dose of INC280, EGF816 or nivolumab. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 18 | 16 | 30 |
| Count of Participants [Participants] |
7
38.9%
|
4
25%
|
5
16.7%
|
| Title | Disease Control Rate (DCR) Per RECIST v1.1 |
|---|---|
| Description | Tumor response was based on local investigator assessment as per RECIST v1.1. DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD). For RECIST v1.1, 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. |
| Time Frame | From start of treatment until end of treatment, assessed up to 4.7 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had received at least 1 dose of INC280, EGF816 or nivolumab. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 18 | 16 | 30 |
| Count of Participants [Participants] |
17
94.4%
|
13
81.3%
|
13
43.3%
|
| Title | Median Progression-Free Survival (PFS) Per RECIST v1.1 |
|---|---|
| Description | PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. The median PFS was estimated using the Kaplan-Meier method. Tumor response was based on local investigator assessment as per RECIST v1.1 |
| Time Frame | From start of treatment to first documented progression or death, assessed up to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had received at least 1 dose of INC280, EGF816 or nivolumab. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 18 | 16 | 30 |
| Median (95% Confidence Interval) [months] |
7.4
|
6.2
|
4.2
|
| Title | Progression-Free Survival (PFS) Rate at 3 Months Per RECIST v1.1 |
|---|---|
| Description | PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The PFS rate at 3 months was estimated using the Kaplan-Meier method. |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had received at least 1 dose of INC280, EGF816 or nivolumab. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 18 | 16 | 30 |
| Number (95% Confidence Interval) [percentage of participants] |
83.3
462.8%
|
86.7
541.9%
|
53.8
179.3%
|
| Title | Overall Survival (OS) at 1 Year |
|---|---|
| Description | OS represents the percentage of participants who are alive after the start of study treatment. OS at 1 year was estimated using the Kaplan-Meier method. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had received at least 1 dose of INC280, EGF816 or nivolumab. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 18 | 16 | 30 |
| Number (95% Confidence Interval) [percentage of participants] |
55.6
308.9%
|
72.3
451.9%
|
32.5
108.3%
|
| Title | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. AE grades were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. |
| Time Frame | From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had received at least 1 dose of INC280, EGF816 or nivolumab and had at least 1 valid post-baseline safety assessment. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 18 | 16 | 30 |
| AEs |
18
100%
|
16
100%
|
30
100%
|
| Treatment-related AEs |
17
94.4%
|
16
100%
|
27
90%
|
| AEs with grade 3/4 |
18
100%
|
14
87.5%
|
24
80%
|
| Treatment-related AEs with grade 3/4 |
13
72.2%
|
12
75%
|
16
53.3%
|
| SAEs |
14
77.8%
|
8
50%
|
18
60%
|
| Treatment-related SAEs |
6
33.3%
|
4
25%
|
7
23.3%
|
| Fatal SAEs |
4
22.2%
|
1
6.3%
|
4
13.3%
|
| Treatment related fatal SAEs |
2
11.1%
|
0
0%
|
0
0%
|
| AEs leading to discontinuation |
5
27.8%
|
7
43.8%
|
11
36.7%
|
| Treatment-related AEs leading to discontinuation |
5
27.8%
|
7
43.8%
|
9
30%
|
| AEs leading to dose adjustment/interruption |
15
83.3%
|
14
87.5%
|
23
76.7%
|
| Title | Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab |
|---|---|
| Description | Number of participants with at least one dose reduction of EGF816, INC280 or nivolumab and number of participants with at least one dose interruption of EGF816, INC280 or nivolumab. Dose reduction was not allowed for nivolumab in this study. |
| Time Frame | From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had received at least 1 dose of INC280, EGF816 or nivolumab and had at least 1 valid post-baseline safety assessment. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 18 | 16 | 30 |
| EGF816, dose reduction |
5
27.8%
|
||
| EGF816, dose interruption |
14
77.8%
|
||
| INC280, dose reduction |
7
38.9%
|
10
62.5%
|
|
| INC280, dose interruption |
14
77.8%
|
25
156.3%
|
|
| Nivolumab, dose reduction |
0
0%
|
0
0%
|
0
0%
|
| Nivolumab, dose interruption |
12
66.7%
|
10
62.5%
|
15
50%
|
| Title | Dose Intensity of EGF816 and INC280 |
|---|---|
| Description | Dose intensity (mg/day) of EGF816 and INC280 was calculated as actual cumulative dose in milligrams divided by duration of exposure in days. |
| Time Frame | From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had received at least 1 dose of INC280, EGF816 or nivolumab and had at least 1 valid post-baseline safety assessment. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 18 | 16 | 30 |
| EGF816 |
141.5
|
||
| INC280 |
609.4
|
636.7
|
| Title | Dose Intensity of Nivolumab |
|---|---|
| Description | Dose intensity (mg/kg biweekly) of nivolumab was calculated as actual cumulative dose in mg/kg divided by duration of exposure in days and then multiplied by 14 days (2 weeks). |
| Time Frame | From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had received at least 1 dose of INC280, EGF816 or nivolumab and had at least 1 valid post-baseline safety assessment. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 18 | 16 | 30 |
| Median (Full Range) [mg/kg/2-week] |
3.0
|
3.0
|
3.0
|
| Title | Maximum Observed Plasma Concentration (Cmax) of EGF816 |
|---|---|
| Description | Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose. |
| Time Frame | pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had extensive PK sampling and provided an EGF816 evaluable PK profile on Cycle 1 Day 15. The EGF816 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). |
| Arm/Group Title | Nivolumab and EGF816 |
|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 11 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
935
(40.8)
|
| Title | Time to Reach Maximum Plasma Concentration (Tmax) of EGF816 |
|---|---|
| Description | Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. |
| Time Frame | pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had extensive PK sampling and provided an EGF816 evaluable PK profile on Cycle 1 Day 15. The EGF816 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). |
| Arm/Group Title | Nivolumab and EGF816 |
|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 11 |
| Median (Full Range) [hours] |
3.00
|
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of EGF816 |
|---|---|
| Description | Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation. |
| Time Frame | pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had extensive PK sampling and provided an EGF816 evaluable PK profile on Cycle 1 Day 15. The EGF816 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). |
| Arm/Group Title | Nivolumab and EGF816 |
|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 11 |
| Geometric Mean (Geometric Coefficient of Variation) [hr*ng/mL] |
5560
(42.8)
|
| Title | Minimum Observed Plasma Concentration (Cmin) of EGF816 |
|---|---|
| Description | Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Cmin is defined as the minimum observed plasma concentration following a dose. |
| Time Frame | pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had extensive PK sampling and provided an EGF816 evaluable PK profile on Cycle 1 Day 15. The EGF816 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). |
| Arm/Group Title | Nivolumab and EGF816 |
|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 11 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
398
(48.8)
|
| Title | Maximum Observed Plasma Concentration (Cmax) of INC280 |
|---|---|
| Description | Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose. |
| Time Frame | pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had extensive PK sampling and provided an INC280 evaluable PK profile on Cycle 1 Day 15. The INC280 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). In the Group 2B, no patients provided an INC280 evaluable PK profile. |
| Arm/Group Title | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|
| Arm/Group Description | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 5 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
6190
(83.9)
|
| Title | Time to Reach Maximum Plasma Concentration (Tmax) of INC280 |
|---|---|
| Description | Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations. |
| Time Frame | pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had extensive PK sampling and provided an INC280 evaluable PK profile on Cycle 1 Day 15. The INC280 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). In the Group 2B, no patients provided an INC280 evaluable PK profile. |
| Arm/Group Title | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|
| Arm/Group Description | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 5 | 0 |
| Median (Full Range) [hours] |
0.983
|
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of INC280 |
|---|---|
| Description | Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation. |
| Time Frame | pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had extensive PK sampling and provided an INC280 evaluable PK profile on Cycle 1 Day 15. The INC280 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). In the Group 2B, no patients provided an INC280 evaluable PK profile. |
| Arm/Group Title | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|
| Arm/Group Description | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 5 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [hr*ng/mL] |
19300
(97.5)
|
| Title | Minimum Observed Plasma Concentration (Cmin) of INC280 |
|---|---|
| Description | Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Cmin is defined as the minimum observed plasma concentration following a dose. |
| Time Frame | pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had extensive PK sampling and provided an INC280 evaluable PK profile on Cycle 1 Day 15. The INC280 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). In the Group 2B, no patients provided an INC280 evaluable PK profile. |
| Arm/Group Title | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|
| Arm/Group Description | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 5 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
428
(105)
|
| Title | Pre-dose Serum Concentration of Nivolumab |
|---|---|
| Description | Nivolumab serum concentrations were assessed in samples taken at pre-dose. Pre-dose samples were collected before the next dose administration. |
| Time Frame | pre-dose on Cycle 1 Day 1 (groups 2A and 2B only) and pre-dose on Cycle 1 Day 15 and Cycle 2 Day 1 (all groups). The duration of one cycle was 28 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who had provided at least 1 evaluable nivolumab PK concentration. For a nivolumab PK concentration to be evaluable in pre-dose samples, a patient was required to have the sample collected before the next dose administration. Samples were not collected in Group 1 on Cycle 1 Day 1. |
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet |
|---|---|---|---|
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
| Measure Participants | 18 | 15 | 29 |
| Cycle 1 Day 1 |
NA
(NA)
|
NA
(NA)
|
|
| Cycle 1 Day 15 |
17.2
(28.6)
|
18.6
(45.3)
|
19.5
(35.6)
|
| Cycle 2 Day 1 |
21.3
(54.6)
|
35.7
(26.6)
|
26.4
(77.1)
|
Adverse Events
| Time Frame | From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Any sign or symptom that occurs during the study treatment plus 100 days after last dose. | |||||||
| Arm/Group Title | Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet | Nivolumab and INC280, High+Low cMet | ||||
| Arm/Group Description | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W | Group 2A+2B (low and high cMet): INC280 400 mg BID + Nivolumab 3 mg/kg Q2W | ||||
All Cause Mortality |
||||||||
| Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet | Nivolumab and INC280, High+Low cMet | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/18 (44.4%) | 4/16 (25%) | 10/30 (33.3%) | 14/46 (30.4%) | ||||
Serious Adverse Events |
||||||||
| Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet | Nivolumab and INC280, High+Low cMet | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/18 (77.8%) | 8/16 (50%) | 18/30 (60%) | 26/46 (56.5%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Disseminated intravascular coagulation | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Neutropenia | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Thrombocytopenia | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Cardiac disorders | ||||||||
| Acute myocardial infarction | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Angina pectoris | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Myocardial infarction | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Sinus tachycardia | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Endocrine disorders | ||||||||
| Adrenal insufficiency | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Eye disorders | ||||||||
| Diplopia | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Abdominal pain upper | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Colitis | 1/18 (5.6%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Diarrhoea | 0/18 (0%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Gastrooesophageal reflux disease | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Pancreatitis | 1/18 (5.6%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Vomiting | 0/18 (0%) | 1/16 (6.3%) | 2/30 (6.7%) | 3/46 (6.5%) | ||||
| General disorders | ||||||||
| Condition aggravated | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Fatigue | 1/18 (5.6%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Gait disturbance | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| General physical health deterioration | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Pyrexia | 4/18 (22.2%) | 1/16 (6.3%) | 3/30 (10%) | 4/46 (8.7%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatic function abnormal | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Immune system disorders | ||||||||
| Anaphylactic reaction | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Contrast media allergy | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Infections and infestations | ||||||||
| Abdominal wall abscess | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Bacterial infection | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Bronchitis | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Pneumonia | 1/18 (5.6%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Respiratory tract infection | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Upper respiratory tract infection | 1/18 (5.6%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Urinary tract infection | 1/18 (5.6%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Investigations | ||||||||
| Blood creatinine increased | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Diabetic ketoacidosis | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Hyperamylasaemia | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Back pain | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Bone pain | 1/18 (5.6%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Myositis | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Metastases to meninges | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Nervous system disorders | ||||||||
| Ataxia | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Cerebral ischaemia | 1/18 (5.6%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Cerebrovascular accident | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Dysaesthesia | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Dysarthria | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Headache | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Hemiparesis | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Ischaemic stroke | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Lethargy | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Somnolence | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Syncope | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Psychiatric disorders | ||||||||
| Confusional state | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Bronchospasm | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Dyspnoea | 2/18 (11.1%) | 2/16 (12.5%) | 2/30 (6.7%) | 4/46 (8.7%) | ||||
| Interstitial lung disease | 3/18 (16.7%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Pleural effusion | 2/18 (11.1%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Pneumonitis | 1/18 (5.6%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Pneumothorax | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Pulmonary embolism | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Pulmonary oedema | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Respiratory failure | 1/18 (5.6%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Tachypnoea | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Pruritus | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Rash macular | 0/18 (0%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Rash maculo-papular | 1/18 (5.6%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Stevens-Johnson syndrome | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Vascular disorders | ||||||||
| Giant cell arteritis | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Nivolumab and EGF816 | Nivolumab and INC280, High cMet | Nivolumab and INC280, Low cMet | Nivolumab and INC280, High+Low cMet | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/18 (100%) | 16/16 (100%) | 29/30 (96.7%) | 45/46 (97.8%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 4/18 (22.2%) | 4/16 (25%) | 7/30 (23.3%) | 11/46 (23.9%) | ||||
| Leukopenia | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Neutropenia | 1/18 (5.6%) | 1/16 (6.3%) | 2/30 (6.7%) | 3/46 (6.5%) | ||||
| Thrombocytopenia | 2/18 (11.1%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Cardiac disorders | ||||||||
| Extrasystoles | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Tachycardia | 0/18 (0%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Ear and labyrinth disorders | ||||||||
| Deafness | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Tinnitus | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Endocrine disorders | ||||||||
| Hyperthyroidism | 0/18 (0%) | 2/16 (12.5%) | 0/30 (0%) | 2/46 (4.3%) | ||||
| Hypophysitis | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Hypothyroidism | 1/18 (5.6%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Eye disorders | ||||||||
| Dry eye | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Uveitis | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Vision blurred | 1/18 (5.6%) | 2/16 (12.5%) | 0/30 (0%) | 2/46 (4.3%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 2/18 (11.1%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Abdominal pain upper | 2/18 (11.1%) | 1/16 (6.3%) | 3/30 (10%) | 4/46 (8.7%) | ||||
| Anal haemorrhage | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Aphthous ulcer | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Ascites | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Constipation | 3/18 (16.7%) | 5/16 (31.3%) | 2/30 (6.7%) | 7/46 (15.2%) | ||||
| Diarrhoea | 9/18 (50%) | 5/16 (31.3%) | 6/30 (20%) | 11/46 (23.9%) | ||||
| Dry mouth | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Dysphagia | 1/18 (5.6%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Faeces discoloured | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Gastrooesophageal reflux disease | 0/18 (0%) | 2/16 (12.5%) | 1/30 (3.3%) | 3/46 (6.5%) | ||||
| Nausea | 5/18 (27.8%) | 13/16 (81.3%) | 12/30 (40%) | 25/46 (54.3%) | ||||
| Oesophageal pain | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Stomatitis | 3/18 (16.7%) | 1/16 (6.3%) | 2/30 (6.7%) | 3/46 (6.5%) | ||||
| Toothache | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Vomiting | 5/18 (27.8%) | 9/16 (56.3%) | 7/30 (23.3%) | 16/46 (34.8%) | ||||
| General disorders | ||||||||
| Asthenia | 7/18 (38.9%) | 6/16 (37.5%) | 10/30 (33.3%) | 16/46 (34.8%) | ||||
| Catheter site swelling | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Chest discomfort | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Chills | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Face oedema | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Fatigue | 3/18 (16.7%) | 5/16 (31.3%) | 4/30 (13.3%) | 9/46 (19.6%) | ||||
| Gait disturbance | 2/18 (11.1%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Influenza like illness | 0/18 (0%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Non-cardiac chest pain | 0/18 (0%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Oedema | 0/18 (0%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Oedema peripheral | 1/18 (5.6%) | 8/16 (50%) | 8/30 (26.7%) | 16/46 (34.8%) | ||||
| Pain | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Peripheral swelling | 1/18 (5.6%) | 2/16 (12.5%) | 0/30 (0%) | 2/46 (4.3%) | ||||
| Pyrexia | 10/18 (55.6%) | 6/16 (37.5%) | 3/30 (10%) | 9/46 (19.6%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholecystitis | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Hepatic pain | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Infections and infestations | ||||||||
| Abdominal wall abscess | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Bronchitis | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Candida infection | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Cellulitis | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Conjunctivitis | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Cystitis bacterial | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Dermatitis infected | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Herpes simplex | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Herpes zoster | 0/18 (0%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Influenza | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Lower respiratory tract infection | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Nasopharyngitis | 1/18 (5.6%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Oesophageal candidiasis | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Oral candidiasis | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Paronychia | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Pneumonia | 2/18 (11.1%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Pulpitis dental | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Respiratory tract infection viral | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Sinusitis | 0/18 (0%) | 2/16 (12.5%) | 0/30 (0%) | 2/46 (4.3%) | ||||
| Upper respiratory tract infection | 2/18 (11.1%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Urinary tract infection | 1/18 (5.6%) | 2/16 (12.5%) | 1/30 (3.3%) | 3/46 (6.5%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Femur fracture | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Limb injury | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Lumbar vertebral fracture | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Muscle injury | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Procedural pain | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/18 (0%) | 2/16 (12.5%) | 5/30 (16.7%) | 7/46 (15.2%) | ||||
| Amylase increased | 6/18 (33.3%) | 9/16 (56.3%) | 6/30 (20%) | 15/46 (32.6%) | ||||
| Aspartate aminotransferase increased | 0/18 (0%) | 1/16 (6.3%) | 5/30 (16.7%) | 6/46 (13%) | ||||
| Bilirubin conjugated increased | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Blood albumin decreased | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Blood alkaline phosphatase increased | 0/18 (0%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Blood bilirubin increased | 0/18 (0%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Blood creatine phosphokinase increased | 0/18 (0%) | 0/16 (0%) | 6/30 (20%) | 6/46 (13%) | ||||
| Blood creatinine increased | 0/18 (0%) | 6/16 (37.5%) | 9/30 (30%) | 15/46 (32.6%) | ||||
| Blood glucose increased | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Blood triglycerides increased | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| C-reactive protein increased | 0/18 (0%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Gamma-glutamyltransferase increased | 0/18 (0%) | 3/16 (18.8%) | 0/30 (0%) | 3/46 (6.5%) | ||||
| Lipase increased | 4/18 (22.2%) | 7/16 (43.8%) | 6/30 (20%) | 13/46 (28.3%) | ||||
| Lymphocyte count decreased | 0/18 (0%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Platelet count decreased | 0/18 (0%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Transaminases increased | 0/18 (0%) | 1/16 (6.3%) | 2/30 (6.7%) | 3/46 (6.5%) | ||||
| Weight decreased | 3/18 (16.7%) | 2/16 (12.5%) | 2/30 (6.7%) | 4/46 (8.7%) | ||||
| White blood cell count decreased | 0/18 (0%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Cell death | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Decreased appetite | 6/18 (33.3%) | 2/16 (12.5%) | 9/30 (30%) | 11/46 (23.9%) | ||||
| Hypercalcaemia | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Hyperkalaemia | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Hyperuricaemia | 2/18 (11.1%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Hypoalbuminaemia | 0/18 (0%) | 2/16 (12.5%) | 9/30 (30%) | 11/46 (23.9%) | ||||
| Hypocalcaemia | 2/18 (11.1%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Hypochloraemia | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Hypokalaemia | 3/18 (16.7%) | 2/16 (12.5%) | 7/30 (23.3%) | 9/46 (19.6%) | ||||
| Hypomagnesaemia | 1/18 (5.6%) | 2/16 (12.5%) | 3/30 (10%) | 5/46 (10.9%) | ||||
| Hyponatraemia | 1/18 (5.6%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Hypophosphataemia | 0/18 (0%) | 2/16 (12.5%) | 0/30 (0%) | 2/46 (4.3%) | ||||
| Hypoproteinaemia | 0/18 (0%) | 2/16 (12.5%) | 0/30 (0%) | 2/46 (4.3%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 4/18 (22.2%) | 5/16 (31.3%) | 4/30 (13.3%) | 9/46 (19.6%) | ||||
| Arthritis | 0/18 (0%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Back pain | 1/18 (5.6%) | 3/16 (18.8%) | 3/30 (10%) | 6/46 (13%) | ||||
| Bone pain | 1/18 (5.6%) | 1/16 (6.3%) | 2/30 (6.7%) | 3/46 (6.5%) | ||||
| Muscle contracture | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Muscle spasms | 2/18 (11.1%) | 2/16 (12.5%) | 1/30 (3.3%) | 3/46 (6.5%) | ||||
| Muscular weakness | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Musculoskeletal chest pain | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Musculoskeletal pain | 1/18 (5.6%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Musculoskeletal stiffness | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Myalgia | 0/18 (0%) | 3/16 (18.8%) | 3/30 (10%) | 6/46 (13%) | ||||
| Pain in extremity | 1/18 (5.6%) | 1/16 (6.3%) | 3/30 (10%) | 4/46 (8.7%) | ||||
| Spinal pain | 1/18 (5.6%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Benign neoplasm | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Cancer pain | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Infected naevus | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Metastases to meninges | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Nervous system disorders | ||||||||
| Balance disorder | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Cerebral ischaemia | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Dizziness | 3/18 (16.7%) | 1/16 (6.3%) | 3/30 (10%) | 4/46 (8.7%) | ||||
| Dysaesthesia | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Dysgeusia | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Essential tremor | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Headache | 4/18 (22.2%) | 5/16 (31.3%) | 0/30 (0%) | 5/46 (10.9%) | ||||
| Hydrocephalus | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Lethargy | 0/18 (0%) | 0/16 (0%) | 2/30 (6.7%) | 2/46 (4.3%) | ||||
| Nervous system disorder | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Paraesthesia | 2/18 (11.1%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Peripheral sensory neuropathy | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Presyncope | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Sciatica | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Seizure | 1/18 (5.6%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Somnolence | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Speech disorder | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Spinal cord compression | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Tremor | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Product Issues | ||||||||
| Device occlusion | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Thrombosis in device | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 0/18 (0%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Insomnia | 2/18 (11.1%) | 2/16 (12.5%) | 1/30 (3.3%) | 3/46 (6.5%) | ||||
| Suicidal ideation | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Renal and urinary disorders | ||||||||
| Dysuria | 2/18 (11.1%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Pollakiuria | 3/18 (16.7%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Renal failure | 1/18 (5.6%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Renal impairment | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Urinary incontinence | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Breast haematoma | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Cystocele | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Genital ulceration | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Pelvic pain | 2/18 (11.1%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Perineal fistula | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Vulvovaginal discomfort | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Vulvovaginal pruritus | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 4/18 (22.2%) | 3/16 (18.8%) | 4/30 (13.3%) | 7/46 (15.2%) | ||||
| Dysphonia | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Dyspnoea | 4/18 (22.2%) | 2/16 (12.5%) | 7/30 (23.3%) | 9/46 (19.6%) | ||||
| Dyspnoea exertional | 1/18 (5.6%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Epistaxis | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Haemoptysis | 1/18 (5.6%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Nasal dryness | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Pleural effusion | 0/18 (0%) | 2/16 (12.5%) | 2/30 (6.7%) | 4/46 (8.7%) | ||||
| Pneumonitis | 0/18 (0%) | 1/16 (6.3%) | 1/30 (3.3%) | 2/46 (4.3%) | ||||
| Sleep apnoea syndrome | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Actinic keratosis | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Alopecia | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Dermatitis acneiform | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Dermatitis exfoliative | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Dry skin | 4/18 (22.2%) | 2/16 (12.5%) | 2/30 (6.7%) | 4/46 (8.7%) | ||||
| Ecchymosis | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Eczema | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Erythema | 2/18 (11.1%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Hyperhidrosis | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Lichenoid keratosis | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Nail disorder | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Nail dystrophy | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Onychoclasis | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Pain of skin | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Palmar erythema | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Pruritus | 6/18 (33.3%) | 2/16 (12.5%) | 4/30 (13.3%) | 6/46 (13%) | ||||
| Rash | 12/18 (66.7%) | 3/16 (18.8%) | 4/30 (13.3%) | 7/46 (15.2%) | ||||
| Rash erythematous | 2/18 (11.1%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Rash maculo-papular | 3/18 (16.7%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Rash pruritic | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Skin exfoliation | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Skin fissures | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Urticaria | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Vascular disorders | ||||||||
| Giant cell arteritis | 0/18 (0%) | 1/16 (6.3%) | 0/30 (0%) | 1/46 (2.2%) | ||||
| Haematoma | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
| Hypertension | 1/18 (5.6%) | 0/16 (0%) | 1/30 (3.3%) | 1/46 (2.2%) | ||||
| Peripheral ischaemia | 1/18 (5.6%) | 0/16 (0%) | 0/30 (0%) | 0/46 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 (ie, data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02323126
Other Study ID Numbers:
- CEGF816X2201C
- 2014-003731-20
First Posted:
Dec 23, 2014
Last Update Posted:
Feb 28, 2022
Last Verified:
Jan 1, 2022