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

NCT ID: NCT03333343

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

105 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-29

Study Completion Date

2026-03-09

Brief Summary

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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 Epidermal growth factor receptor- mutant (EGFR-mutant) non-small cell lung cancer (NSCLC).

Detailed Description

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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 were 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 could be enrolled to the dose expansion arms of each of these combinations. Patients could also be assigned to EGF816 + INC280. The planned arm EGF816 + gefitinib in dose expansion was not opened for enrollment.

Conditions

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EGFR-mutant Non-small Cell Lung Cancer

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

EGF816+ trametinib in escalation phase

Group Type EXPERIMENTAL

EGF816

Intervention Type DRUG

Study Drug

trametinib

Intervention Type DRUG

Study Drug

Arm 2

EGF816 + ribociclib in escalation phase

Group Type EXPERIMENTAL

EGF816

Intervention Type DRUG

Study Drug

ribociclib

Intervention Type DRUG

Study Drug

Arm 3

EGF816 + LXH254 in escalation phase

Group Type EXPERIMENTAL

EGF816

Intervention Type DRUG

Study Drug

LXH254

Intervention Type DRUG

Study Drug

Arm A

EGF816 + INC280 in expansion phase (patients with no known resistance mechanism)

Group Type EXPERIMENTAL

EGF816

Intervention Type DRUG

Study Drug

INC280

Intervention Type DRUG

Study Drug

Arm B

EGF816 + trametinib in expansion phase

Group Type EXPERIMENTAL

EGF816

Intervention Type DRUG

Study Drug

trametinib

Intervention Type DRUG

Study Drug

Arm C

EGF816 + ribociclib in expansion phase

Group Type EXPERIMENTAL

EGF816

Intervention Type DRUG

Study Drug

ribociclib

Intervention Type DRUG

Study Drug

Arm D

EGF816 + LXH254 in expansion phase (patients with no known resistance mechanism)

Group Type EXPERIMENTAL

EGF816

Intervention Type DRUG

Study Drug

LXH254

Intervention Type DRUG

Study Drug

Arm E

EGF816 + LXH254 in expansion phase (patients with known resistance mechanism)

Group Type EXPERIMENTAL

EGF816

Intervention Type DRUG

Study Drug

LXH254

Intervention Type DRUG

Study Drug

Arm F

EGF816 + gefitinib in expansion phase

Group Type EXPERIMENTAL

EGF816

Intervention Type DRUG

Study Drug

gefitinib

Intervention Type DRUG

Study Drug

Arm G

EGF816 + INC280 in expansion phase (patients with known resistance mechanism)

Group Type EXPERIMENTAL

EGF816

Intervention Type DRUG

Study Drug

INC280

Intervention Type DRUG

Study Drug

Interventions

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EGF816

Study Drug

Intervention Type DRUG

trametinib

Study Drug

Intervention Type DRUG

ribociclib

Study Drug

Intervention Type DRUG

LXH254

Study Drug

Intervention Type DRUG

INC280

Study Drug

Intervention Type DRUG

gefitinib

Study Drug

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_CHAIR

Novartis

Locations

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Novartis Investigative Site

Toronto, Ontario, Canada

Site Status

Novartis Investigative Site

Cologne, North Rhine-Westphalia, Germany

Site Status

Novartis Investigative Site

Essen, , Germany

Site Status

Novartis Investigative Site

Hong Kong, , Hong Kong

Site Status

Novartis Investigative Site

Ancona, AN, Italy

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Rozzano, MI, Italy

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Tainan, , Taiwan

Site Status

Novartis Investigative Site

Taipei, , Taiwan

Site Status

Countries

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Spain United States Canada Germany Hong Kong Italy Singapore Taiwan

Other Identifiers

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2024-511757-21-00

Identifier Type: OTHER

Identifier Source: secondary_id

CEGF816X2102

Identifier Type: -

Identifier Source: org_study_id