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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02323126




Registration number
NCT02323126
Ethics application status
Date submitted
18/12/2014
Date registered
23/12/2014

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2014-003731-20
Secondary ID [2] 0 0
CEGF816X2201C
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EGF816
Treatment: Drugs - INC280
Treatment: Drugs - Nivolumab

Experimental: Nivolumab and EGF816 - Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W

Experimental: Nivolumab and INC280, high cMet - Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W

Experimental: Nivolumab and INC280, low cMet - Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W


Treatment: Drugs: EGF816
EGF816 150 mg once daily (QD) administered orally as a capsule

Treatment: Drugs: INC280
INC280 400 mg twice daily (BID) administered orally as a tablet

Treatment: Drugs: Nivolumab
Nivolumab 3 mg/kg every 2 weeks (Q2W) administered by intravenous infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) Rate at 6 Months Per RECIST v1.1
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Overall Response Rate (ORR) Per RECIST v1.1
Timepoint [1] 0 0
From start of treatment until end of treatment, assessed up to 4.7 years
Secondary outcome [2] 0 0
Disease Control Rate (DCR) Per RECIST v1.1
Timepoint [2] 0 0
From start of treatment until end of treatment, assessed up to 4.7 years
Secondary outcome [3] 0 0
Median Progression-Free Survival (PFS) Per RECIST v1.1
Timepoint [3] 0 0
From start of treatment to first documented progression or death, assessed up to 5 years
Secondary outcome [4] 0 0
Progression-Free Survival (PFS) Rate at 3 Months Per RECIST v1.1
Timepoint [4] 0 0
3 months
Secondary outcome [5] 0 0
Overall Survival (OS) at 1 Year
Timepoint [5] 0 0
1 year
Secondary outcome [6] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [6] 0 0
From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years
Secondary outcome [7] 0 0
Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab
Timepoint [7] 0 0
From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years
Secondary outcome [8] 0 0
Dose Intensity of EGF816 and INC280
Timepoint [8] 0 0
From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years
Secondary outcome [9] 0 0
Dose Intensity of Nivolumab
Timepoint [9] 0 0
From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years
Secondary outcome [10] 0 0
Maximum Observed Plasma Concentration (Cmax) of EGF816
Timepoint [10] 0 0
pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Secondary outcome [11] 0 0
Time to Reach Maximum Plasma Concentration (Tmax) of EGF816
Timepoint [11] 0 0
pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Secondary outcome [12] 0 0
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of EGF816
Timepoint [12] 0 0
pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Secondary outcome [13] 0 0
Minimum Observed Plasma Concentration (Cmin) of EGF816
Timepoint [13] 0 0
pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Secondary outcome [14] 0 0
Maximum Observed Plasma Concentration (Cmax) of INC280
Timepoint [14] 0 0
pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Secondary outcome [15] 0 0
Time to Reach Maximum Plasma Concentration (Tmax) of INC280
Timepoint [15] 0 0
pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Secondary outcome [16] 0 0
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of INC280
Timepoint [16] 0 0
pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Secondary outcome [17] 0 0
Minimum Observed Plasma Concentration (Cmin) of INC280
Timepoint [17] 0 0
pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Secondary outcome [18] 0 0
Pre-dose Serum Concentration of Nivolumab
Timepoint [18] 0 0
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.

Eligibility
Key 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 2) 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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/02/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/02/2021
Sample size
Target
Accrual to date
Final
64
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Novartis Investigative Site - Camperdown
Recruitment hospital [2] 0 0
Novartis Investigative Site - Chermside
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
France
State/province [2] 0 0
La Tronche
Country [3] 0 0
Germany
State/province [3] 0 0
Nordrhein-Westfalen
Country [4] 0 0
Italy
State/province [4] 0 0
PG
Country [5] 0 0
Italy
State/province [5] 0 0
PN
Country [6] 0 0
Singapore
State/province [6] 0 0
Singapore
Country [7] 0 0
Spain
State/province [7] 0 0
Andalucia
Country [8] 0 0
Spain
State/province [8] 0 0
Catalunya
Country [9] 0 0
Spain
State/province [9] 0 0
Comunidad Valenciana
Country [10] 0 0
Spain
State/province [10] 0 0
Madrid
Country [11] 0 0
Switzerland
State/province [11] 0 0
Chur

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02323126