Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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 )

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.

Condition or disease Intervention/treatment Phase
EGFR-mutant Non-small Cell Lung Cancer Drug: EGF816 Drug: trametinib Drug: ribociclib Drug: LXH254 Drug: INC280 Drug: gefitinib Phase 1

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 157 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 29, 2018
Estimated Primary Completion Date : May 21, 2021
Estimated Study Completion Date : May 21, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1
EGF816+ trametinib in escalation phase
Drug: EGF816
Study Drug

Drug: trametinib
Study Drug

Experimental: Arm 2
EGF816 + ribociclib in escalation phase
Drug: EGF816
Study Drug

Drug: ribociclib
Study Drug

Experimental: Arm 3
EGF816 + LXH254 in escalation phase
Drug: EGF816
Study Drug

Drug: LXH254
Study Drug

Experimental: Arm A
EGF816 + INC280 in expansion phase (patients with no known resistance mechanism)
Drug: EGF816
Study Drug

Drug: INC280
Study Drug

Experimental: Arm B
EGF816 + trametinib in expansion phase
Drug: EGF816
Study Drug

Drug: trametinib
Study Drug

Experimental: Arm C
EGF816 + ribociclib in expansion phase
Drug: EGF816
Study Drug

Drug: ribociclib
Study Drug

Experimental: Arm D
EGF816 + LXH254 in expansion phase (patients with no known resistance mechanism)
Drug: EGF816
Study Drug

Drug: LXH254
Study Drug

Experimental: Arm E
EGF816 + LXH254 in expansion phase (patients with known resistance mechanism)
Drug: EGF816
Study Drug

Drug: LXH254
Study Drug

Experimental: Arm F
EGF816 + gefitinib in expansion phase
Drug: EGF816
Study Drug

Drug: gefitinib
Study Drug

Experimental: Arm G
EGF816 + INC280 in expansion phase (patients with known resistance mechanism)
Drug: EGF816
Study Drug

Drug: INC280
Study Drug




Primary Outcome Measures :
  1. 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.

  2. 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)


Secondary Outcome Measures :
  1. ORR [ Time Frame: Every 8-12 weeks until study ends, approximately 4 years ]
    Overall response rate (ORR) per RECIST v1.1

  2. 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

  3. 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

  4. 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

  5. Time to response [ Time Frame: Every 8-12 weeks until study ends, approximately 4 years ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03333343


Contacts
Layout table for location contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
Layout table for location information
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Germany
Novartis Investigative Site Recruiting
Koeln, Germany, 50937
Italy
Novartis Investigative Site Recruiting
Ancona, AN, Italy, 60126
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20162
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Taiwan
Novartis Investigative Site Recruiting
Tainan, Taiwan, 70421
Novartis Investigative Site Recruiting
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Chair: Novartis Pharmaceuticals Novartis

Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03333343     History of Changes
Other Study ID Numbers: CEGF816X2102
2017-002496-25 ( EudraCT Number )
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: August 27, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
EGFR-mutant NSCLC
EGF816
LXH254
INC280
ribociclib
trametinib
gefitinib
EGFR T790M
BRAF mutation
BRAF fusion
BRAF rearrangement
MET amplification
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gefitinib
Trametinib
(R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo(d)imidazol-2-yl)-2-methylisonicotinamide
Nicotine
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents