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Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC

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ClinicalTrials.gov Identifier: NCT03333343
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : August 27, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE October 31, 2017
First Posted Date  ICMJE November 6, 2017
Last Update Posted Date August 27, 2018
Actual Study Start Date  ICMJE January 29, 2018
Estimated Primary Completion Date May 21, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 2, 2017)
  • Number of patients with adverse events and serious adverse events [ Time Frame: Every day until study end, approximately 4 years ]
    Assess safety and tolerability including incidence of dose limiting toxicities, adverse events, and serious adverse events.
  • ORR2 [ Time Frame: Every 8-12 weeks until study ends, approximately 4 years ]
    Modified objective response rate (ORR2) per RECIST v1.1 (taking as baseline the most recent assessment prior to initiating combination)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03333343 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2017)
  • ORR [ Time Frame: Every 8-12 weeks until study ends, approximately 4 years ]
    Overall response rate (ORR) per RECIST v1.1
  • PFS [ Time Frame: Every 8-12 weeks until study ends, approximately 4 years ]
    Time from the date of first dose of study treatment to the date of first documented disease progression (per RECIST v1.1) or death due to any cause
  • DCR [ Time Frame: Every 8-12 weeks until study ends, approximately 4 years ]
    Proportion of patients with best overall response of CR, PR, or SD
  • DOR [ Time Frame: Every 8-12 weeks until study ends, approximately 4 years ]
    Time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause
  • Time to response [ Time Frame: Every 8-12 weeks until study ends, approximately 4 years ]
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 EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC
Official Title  ICMJE A Phase Ib, Open Label, Multi-center Study to Characterize the Safety, Tolerability and Preliminary Efficacy of EGF816 in Combination With Selected Targeted Agents in EGFR Mutant NSCLC
Brief Summary The study purpose is to evaluate the safety, tolerability, and preliminary efficacy of the addition of INC280, trametinib, ribociclib, gefitinib, or LXH254 to EGF816 in adult patients with advanced EGFR-mutant NSCLC.
Detailed Description

This is a Phase Ib, open label, non-randomized dose escalation study of EGF816 in combination with ribociclib, trametinib, or LXH254, followed by dose expansion of EGF816 in combination with ribociclib, trametinib, LXH254, INC280, or gefitinib in adult patients with advanced EGFR-mutant NSCLC.

During the dose escalation part, patients will be assigned to the addition of trametinib, ribociclib, or LXH254 to EGF816.

Following determination of the recommended dose for the combination of EGF816 + trametinib, EGF816 + ribociclib, and EGF816 + LXH254, patients may be enrolled to the dose expansion arms of each of these combinations. Patients may also be assigned to EGF816 + INC280 or EGF816 + gefitinib in dose expansion.

Efficacy assessments will be performed at baseline and every 2 cycles during treatment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE EGFR-mutant Non-small Cell Lung Cancer
Intervention  ICMJE
  • Drug: EGF816
    Study Drug
  • Drug: trametinib
    Study Drug
  • Drug: ribociclib
    Study Drug
  • Drug: LXH254
    Study Drug
  • Drug: INC280
    Study Drug
  • Drug: gefitinib
    Study Drug
Study Arms  ICMJE
  • Experimental: Arm 1
    EGF816+ trametinib in escalation phase
    Interventions:
    • Drug: EGF816
    • Drug: trametinib
  • Experimental: Arm 2
    EGF816 + ribociclib in escalation phase
    Interventions:
    • Drug: EGF816
    • Drug: ribociclib
  • Experimental: Arm 3
    EGF816 + LXH254 in escalation phase
    Interventions:
    • Drug: EGF816
    • Drug: LXH254
  • Experimental: Arm A
    EGF816 + INC280 in expansion phase (patients with no known resistance mechanism)
    Interventions:
    • Drug: EGF816
    • Drug: INC280
  • Experimental: Arm B
    EGF816 + trametinib in expansion phase
    Interventions:
    • Drug: EGF816
    • Drug: trametinib
  • Experimental: Arm C
    EGF816 + ribociclib in expansion phase
    Interventions:
    • Drug: EGF816
    • Drug: ribociclib
  • Experimental: Arm D
    EGF816 + LXH254 in expansion phase (patients with no known resistance mechanism)
    Interventions:
    • Drug: EGF816
    • Drug: LXH254
  • Experimental: Arm E
    EGF816 + LXH254 in expansion phase (patients with known resistance mechanism)
    Interventions:
    • Drug: EGF816
    • Drug: LXH254
  • Experimental: Arm F
    EGF816 + gefitinib in expansion phase
    Interventions:
    • Drug: EGF816
    • Drug: gefitinib
  • Experimental: Arm G
    EGF816 + INC280 in expansion phase (patients with known resistance mechanism)
    Interventions:
    • Drug: EGF816
    • Drug: INC280
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 2, 2017)
157
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 21, 2021
Estimated Primary Completion Date May 21, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed locally advanced (stage IIIB) or metastatic (stage IV) EGFR mutant (ex19del, L858R) NSCLC.
  • Requirements of EGFR mutation status and prior lines of treatment:
  • Treatment naive patients, who have locally advanced or metastatic NSCLC with EGFR sensitizing mutation (e.g., L858R and/or ex19del), have not received any systemic antineoplastic therapy for advanced NSCLC and are eligible to receive EGFR TKI treatment. Patients with EGFR exon 20 insertion/duplication are not eligible. Note: patients who have received only one cycle of chemotherapy in the advanced setting are allowed.
  • Patients who have locally advanced or metastatic NSCLC with EGFR sensitizing mutation AND an acquired T790M mutation (e.g., L858R and/or ex19del, T790M+) following progression on prior treatment with a 1st-generation EGFR TKI or 2nd-generation EGFR TKI. These patients may not have received more than 4 prior lines of antineoplastic therapy in the advanced setting, including EGFR TKI, and may not have received any agent targeting EGFR T790M mutation (i.e., 3rd-generation EGFR TKI).
  • Patients who have locally advanced or metastatic NSCLC with EGFR sensitizing mutation and a "de novo" T790M mutation (i.e., no prior treatment with any agent known to inhibit EGFR including EGFR TKI). These patients may not have received more than 3 prior lines of antineoplastic therapy in the advanced setting, and may not have received any prior 3rd generation EGFR TKI.
  • Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patients must be willing to undergo a new tumor biopsy during therapy on this study, and at screening if an archival tumor sample obtained since the diagnosis of advanced disease (1L patients) or since last treatment failure (2L+ patients) is not available.

Exclusion Criteria:

  • Patients with a history or presence of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis.
  • Patients with unstable brain metastases.
  • Patients with a history of another malignancy.
  • Patients with a known history of human immunodeficiency virus (HIV) seropositivity.
  • Patients with clinically significant, uncontrolled heart disease.
  • Patients participating in additional parallel investigational drug or medical device studies.
  • Prior therapies:
  • Patients who have been treated with EGFR TKI in the adjuvant setting within 6 months, unless acquired EGFR T790M is present in a tumor or blood sample obtained since the discontinuation of the EGFR TKI.
  • Patients who have been treated with prior EGFR TKI targeting T790M (3rd generation).
  • Patients who have been treated with systemic anti-neoplastic therapy within:

    • 2 weeks for fluoropyrimidine monotherapy
    • 6 weeks for nitrosoureas and mitomycin
    • 4 weeks or ≤ 5 half-lives (whichever is shorter) for biological therapy (including monoclonal antibodies) and continuous or intermittent small molecule therapeutics or any other investigational agent
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: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Canada,   Germany,   Italy,   Singapore,   Taiwan
Removed Location Countries Spain,   United States
 
Administrative Information
NCT Number  ICMJE NCT03333343
Other Study ID Numbers  ICMJE CEGF816X2102
2017-002496-25 ( 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: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Novartis Pharmaceuticals Novartis
PRS Account Novartis
Verification Date August 2018

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