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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02323126
Recruitment Status : Active, not recruiting
First Posted : December 23, 2014
Last Update Posted : February 24, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE December 18, 2014
First Posted Date  ICMJE December 23, 2014
Last Update Posted Date February 24, 2021
Actual Study Start Date  ICMJE February 9, 2015
Estimated Primary Completion Date December 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2014)
Progression Free Survival (PFS) rate using RECIST version1.1 [ Time Frame: 6 month ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2014)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: EGF816
  • Drug: INC280
  • Drug: Nivolumab
Study Arms  ICMJE
  • Experimental: Nivolumab and EGF816
    Arm 1 (EGF816 + nivolumab) is currently closed to new enrollment.
    Interventions:
    • Drug: EGF816
    • Drug: Nivolumab
  • Experimental: Nivolumab and INC280
    Arm 2 (INC280 + nivolumab) is open and enrolling as planned.
    Interventions:
    • Drug: INC280
    • Drug: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 8, 2020)
64
Original Estimated Enrollment  ICMJE
 (submitted: December 18, 2014)
100
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Germany,   Italy,   Netherlands,   Singapore,   Spain,   Switzerland,   United States
Removed Location Countries Canada,   Norway
 
Administrative Information
NCT Number  ICMJE NCT02323126
Other Study ID Numbers  ICMJE CEGF816X2201C
2014-003731-20 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP