Clinical Trials /

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

NCT03333343

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: CEGF816X2102
  • SECONDARY ID: 2017-002496-25
  • NCT ID: NCT03333343

Conditions

  • EGFR-mutant Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
EGF816Arm 1
trametinibArm 1
ribociclibArm 2
LXH254Arm 3
INC280Arm A
gefitinibArm F

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalEGF816+ trametinib in escalation phase
  • EGF816
  • trametinib
Arm 2ExperimentalEGF816 + ribociclib in escalation phase
  • EGF816
  • ribociclib
Arm 3ExperimentalEGF816 + LXH254 in escalation phase
  • EGF816
  • LXH254
Arm AExperimentalEGF816 + INC280 in expansion phase (patients with no known resistance mechanism)
  • EGF816
  • INC280
Arm BExperimentalEGF816 + trametinib in expansion phase
  • EGF816
  • trametinib
Arm CExperimentalEGF816 + ribociclib in expansion phase
  • EGF816
  • ribociclib
Arm DExperimentalEGF816 + LXH254 in expansion phase (patients with no known resistance mechanism)
  • EGF816
  • LXH254
Arm EExperimentalEGF816 + LXH254 in expansion phase (patients with known resistance mechanism)
  • EGF816
  • LXH254
Arm FExperimentalEGF816 + gefitinib in expansion phase
  • EGF816
  • gefitinib
Arm GExperimentalEGF816 + INC280 in expansion phase (patients with known resistance mechanism)
  • EGF816
  • INC280

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with adverse events and serious adverse events
Time Frame:Every day until study end, approximately 4 years
Safety Issue:
Description:Assess safety and tolerability including incidence of dose limiting toxicities, adverse events, and serious adverse events.

Secondary Outcome Measures

Measure:ORR
Time Frame:Every 8-12 weeks until study ends, approximately 4 years
Safety Issue:
Description:Overall response rate (ORR) per RECIST v1.1
Measure:PFS
Time Frame:Every 8-12 weeks until study ends, approximately 4 years
Safety Issue:
Description: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
Measure:DCR
Time Frame:Every 8-12 weeks until study ends, approximately 4 years
Safety Issue:
Description:Proportion of patients with best overall response of CR, PR, or SD
Measure:DOR
Time Frame:Every 8-12 weeks until study ends, approximately 4 years
Safety Issue:
Description:Time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause
Measure:Time to response
Time Frame:Every 8-12 weeks until study ends, approximately 4 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • EGFR-mutant NSCLC
  • EGF816
  • LXH254
  • INC280
  • ribociclib
  • trametinib
  • gefitinib
  • EGFR T790M
  • BRAF mutation
  • BRAF fusion
  • BRAF rearrangement
  • MET amplification

Last Updated

November 2, 2017