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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 (EGF816)

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02323126
First received: December 18, 2014
Last updated: June 30, 2017
Last verified: June 2017
  Purpose
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 Intervention Phase
Non Small Cell Lung Cancer Drug: EGF816 Drug: INC280 Drug: Nivolumab Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Progression Free Survival (PFS) rate using RECIST version1.1 [ Time Frame: 6 month ]

Secondary Outcome Measures:
  • Number of participants with Adverse Events (AEs) [ Time Frame: Continuously during study until 100 days after post study treatment ]
    Safety of EGF816 and Nivolumab and INC280 and Nivolumab by looking at hematology and chemistry laboratory parameters, vital signs, and electrocardiograms (ECGs)

  • Objective response rate (ORR) [ Time Frame: 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 ]
  • Disease control rate [ Time Frame: 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 ]
  • Progression free survival [ Time Frame: 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 ]
  • Overall Survival [ Time Frame: Start of treatment until death, average 1 year ]
  • Plasma pharmacokinetic parameters (AUClast, AUC0-t,AUCtau,Cmax, Tmax) [ Time Frame: 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 ]

Estimated Enrollment: 68
Actual Study Start Date: February 9, 2015
Estimated Study Completion Date: April 10, 2022
Estimated Primary Completion Date: June 17, 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nivolumab and EGF816
Arm 1 (EGF816 + nivolumab) is currently closed to new enrollment.
Drug: EGF816 Drug: Nivolumab
Experimental: Nivolumab and INC280
Arm 2 (INC280 + nivolumab) is open and enrolling as planned.
Drug: INC280 Drug: Nivolumab

Detailed Description:

This study has two arms:

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

Arm 2 (INC280 + nivolumab) is open and enrolling as planned.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02323126

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
United States, Alabama
University of Alabama at Birmingham Onc Department Recruiting
Birmingham, Alabama, United States, 35294
Contact: Jolane Gable    205-934-5092    jgable@uab.edu   
Principal Investigator: Francisco Robert         
United States, Massachusetts
Massachusetts General Hospital Mass General Completed
Boston, Massachusetts, United States, 02114
United States, North Carolina
Levine Cancer Institute Oncology Dept Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Tia Riley    980-442-2383    tia.riley@carolinashealthcare.org   
Principal Investigator: Kathryn Mileham         
United States, Texas
University of Texas/MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2) Recruiting
Houston, Texas, United States, 77030-4009
Contact: Justina M. Price    713-794-5325    jusprice@mdanderson.org   
Principal Investigator: Vassiliki A Papadimitrakopoulou         
Australia, New South Wales
Novartis Investigative Site Recruiting
Camperdown, New South Wales, Australia, 2050
Australia, Queensland
Novartis Investigative Site Recruiting
Chermside, Queensland, Australia, 4032
Australia, South Australia
Novartis Investigative Site Recruiting
Adelaide, South Australia, Australia, 5000
France
Novartis Investigative Site Recruiting
Caen Cedex, France, 14021
Novartis Investigative Site Recruiting
La Tronche, France, 38700
Germany
Novartis Investigative Site Recruiting
Koeln, Nordrhein-Westfalen, Germany, 50937
Novartis Investigative Site Recruiting
Würzburg, Germany, 97080
Italy
Novartis Investigative Site Recruiting
Perugia, PG, Italy, 06129
Novartis Investigative Site Recruiting
Pisa, PI, Italy, 56124
Novartis Investigative Site Recruiting
Aviano, PN, Italy, 33081
Netherlands
NKI-AVL, Department of Thoracic-Oncology Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: E.F. Smit, Prof.    0031-20-5122958    e.smit@nki.nl   
Principal Investigator: E.F. Smit, Prof.         
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Spain
Novartis Investigative Site Recruiting
Malaga, Andalucia, Spain, 29010
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Alicante, Comunidad Valenciana, Spain, 03010
Novartis Investigative Site Recruiting
Madrid, Spain, 28040
Switzerland
Novartis Investigative Site Recruiting
Chur, Switzerland, 7000
Novartis Investigative Site Recruiting
Genève, Switzerland, 1211
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02323126     History of Changes
Other Study ID Numbers: CEGF816X2201C
2014-003731-20 ( EudraCT Number )
Study First Received: December 18, 2014
Last Updated: June 30, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

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


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Non small cell lung cancer,
NSCLC,
EGFR-mutated,
EGF816,
INC280,
Nivolumab,
EGFR-T790M NSCLC,
EGFR wild-type (wt),
cMET positive NSCLC,
cMET negative NSCLC

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2017