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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02323126
Ethics application status
Date submitted
18/12/2014
Date registered
23/12/2014
Date last updated
7/02/2020

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
EGF816
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 - Arm 1 (EGF816 + nivolumab) is currently closed to new enrollment.

Experimental: Nivolumab and INC280 - Arm 2 (INC280 + nivolumab) is open and enrolling as planned.


Treatment: Drugs: EGF816


Treatment: Drugs: INC280


Treatment: Drugs: Nivolumab


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) rate using RECIST version1.1
Timepoint [1] 0 0
6 month
Secondary outcome [1] 0 0
Number of participants with Adverse Events (AEs) - Safety of EGF816 and Nivolumab and INC280 and Nivolumab by looking at hematology and chemistry laboratory parameters, vital signs, and electrocardiograms (ECGs)
Timepoint [1] 0 0
Continuously during study until 100 days after post study treatment
Secondary outcome [2] 0 0
Objective response rate (ORR)
Timepoint [2] 0 0
baseline, every 8 weeks up to cycle 12, then every 12 weeks from cycle 13 until disease progression, consent withdrawal or death up to 1 year
Secondary outcome [3] 0 0
Disease control rate
Timepoint [3] 0 0
baseline, every 8 weeks upto cycle 12, then every 12 weeks from cycle 13 until disease progression, consent withdrawal or death up to 1 year
Secondary outcome [4] 0 0
Progression free survival
Timepoint [4] 0 0
baseline, every 8 weeks upto cycle 12, then every 12 weeks from cycle 13 until disease progression, consent withdrawal or death up to 1 year
Secondary outcome [5] 0 0
Overall Survival
Timepoint [5] 0 0
Start of treatment until death, average 1 year
Secondary outcome [6] 0 0
Plasma pharmacokinetic parameters (AUClast, AUC0-t,AUCtau,Cmax, Tmax)
Timepoint [6] 0 0
Cycle 1: Day1, Day 8, Day 15 and Cycle 2: Day 1, Cycle 4: Day 1 Cycle 6: Day 1 and Cycle 8: Day 1 Subsequent cycles (nivolumab only): every 8th cycle until discontinuation of study treatment

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
Gender
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
must have no 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 with interstitial lung disease that is symptomatic or may interfere with the
detection or management of suspected drug-related pulmonary toxicity

Prior therapy:

- 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.

Other protocol-related inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Camperdown
Recruitment hospital [2] 0 0
Novartis Investigative Site - Chermside
Recruitment hospital [3] 0 0
Novartis Investigative Site - Adelaide
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
France
State/province [5] 0 0
Caen Cedex
Country [6] 0 0
France
State/province [6] 0 0
La Tronche
Country [7] 0 0
Germany
State/province [7] 0 0
Nordrhein-Westfalen
Country [8] 0 0
Germany
State/province [8] 0 0
Wuerzburg
Country [9] 0 0
Italy
State/province [9] 0 0
PG
Country [10] 0 0
Italy
State/province [10] 0 0
PI
Country [11] 0 0
Italy
State/province [11] 0 0
PN
Country [12] 0 0
Netherlands
State/province [12] 0 0
Amsterdam
Country [13] 0 0
Singapore
State/province [13] 0 0
Singapore
Country [14] 0 0
Spain
State/province [14] 0 0
Andalucia
Country [15] 0 0
Spain
State/province [15] 0 0
Catalunya
Country [16] 0 0
Spain
State/province [16] 0 0
Comunidad Valenciana
Country [17] 0 0
Spain
State/province [17] 0 0
Madrid
Country [18] 0 0
Switzerland
State/province [18] 0 0
Chur
Country [19] 0 0
Switzerland
State/province [19] 0 0
Geneve

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

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT02323126
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
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
Novartis.email@novartis.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02323126