EGFR-mutant Non-small Cell Lung CancerPhase 1NCT03333343
Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC
A Phase 1 study testing EGF816, trametinib and ribociclib in people with EGFR-mutant Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 11 sites in 6 countries.
Trial 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 Epidermal growth factor receptor- mutant (EGFR-mutant) non-small cell lung cancer (NSCLC). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- EGFR-mutant Non-small Cell Lung Cancer
- What is being tested?
- EGF816, trametinib and ribociclib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 11 sitesin 6 countries
- Study dates
- 29 Jan 2018to 12 Jul 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
11 sites in 6 countries.
11 sites in 6 countries
Italy3 sites
Novartis Investigative Site
Ancona, AN, 60020
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Rozzano, MI, 20089
Germany2 sites
Novartis Investigative Site
Cologne, North Rhine-Westphalia, 50937
Novartis Investigative Site
Essen, 45147
Singapore2 sites
Novartis Investigative Site
Singapore, 119074
Novartis Investigative Site
Singapore, 168583
Taiwan2 sites
Novartis Investigative Site
Tainan, 704302
Novartis Investigative Site
Taipei, 10002
About this study
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
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).
Read the 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 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
- EGFR-mutant Non-small Cell Lung Cancer
- Being tested
- EGF816, trametinib, ribociclib, LXH254, INC280
- Keywords
- EGFR-mutant NSCLC, EGF816, LXH254, INC280, ribociclib, trametinib, gefitinib, EGFR T790M, BRAF mutation, BRAF fusion, BRAF rearrangement, MET amplification
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EGF816Drug
Study Drug
trametinibDrug
Study Drug
ribociclibDrug
Study Drug
LXH254Drug
Study Drug
INC280Drug
Study Drug
gefitinibDrug
Study Drug
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | EGF816+ trametinib in escalation phase Receives: Drug: EGF816; Drug: trametinib |
| Arm 2 | Experimental | EGF816 + ribociclib in escalation phase Receives: Drug: EGF816; Drug: ribociclib |
| Arm 3 | Experimental | EGF816 + LXH254 in escalation phase Receives: Drug: EGF816; Drug: LXH254 |
| Arm A | Experimental | EGF816 + INC280 in expansion phase (patients with no known resistance mechanism) Receives: Drug: EGF816; Drug: INC280 |
| Arm B | Experimental | EGF816 + trametinib in expansion phase Receives: Drug: EGF816; Drug: trametinib |
| Arm C | Experimental | EGF816 + ribociclib in expansion phase Receives: Drug: EGF816; Drug: ribociclib |
| Arm D | Experimental | EGF816 + LXH254 in expansion phase (patients with no known resistance mechanism) Receives: Drug: EGF816; Drug: LXH254 |
| Arm E | Experimental | EGF816 + LXH254 in expansion phase (patients with known resistance mechanism) Receives: Drug: EGF816; Drug: LXH254 |
| Arm F | Experimental | EGF816 + gefitinib in expansion phase Receives: Drug: EGF816; Drug: gefitinib |
| Arm G | Experimental | EGF816 + INC280 in expansion phase (patients with known resistance mechanism) Receives: Drug: EGF816; Drug: INC280 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with adverse events and serious adverse events
Assess safety and tolerability including incidence of dose limiting toxicities, adverse events, and serious adverse events.
Measured: Every day until study end, approximately 4 years
Number of participants with DLTs in the first cycle of combination (Dose escalation only)
A Dose-Limiting Toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications that occurs within the first 28 days of combination treatment during the dose escalation part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Measured: 28 days
Number of participants with dose interruptions and reductions
Assessment of tolerability. For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments may be permitted in order to allow patients to continue the study treatment.
Measured: From first dose until study ends, approximately 4 years
Dose intensity of study drugs
Dose intensity is computed as the ratio of actual cumulative dose received to actual duration of exposure.
Measured: From first dose until study ends, approximately 4 years
ORR2
Modified objective response rate (ORR2) per RECIST v1.1 (taking as baseline the most recent assessment prior to initiating combination)
Measured: Every 8-12 weeks until study ends, approximately 4 years
Secondary outcomes (7)
ORR
Overall response rate (ORR) per RECIST v1.1
Measured: Every 8-12 weeks until study ends, approximately 4 years
PFS
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
Measured: Every 8-12 weeks until study ends, approximately 4 years
DCR
Proportion of patients with best overall response of CR, PR, or SD
Measured: Every 8-12 weeks until study ends, approximately 4 years
DOR
Time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause
Measured: Every 8-12 weeks until study ends, approximately 4 years
Time to response
Time to response is the time between start of treatment until first documented response per RECIST v1.1.
Measured: Every 8-12 weeks until study ends, approximately 4 years
Area under the plasma concentration-time curve (AUC) of study drugs
Pharmacokinetic (PK) parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods.
Measured: From pre-dose up to 8 hours post-dose on Day 15 of Cycle 1. One cycle=28 days.
Maximum observed plasma concentration (Cmax) of study drugs
PK parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods.
Measured: From pre-dose up to 8 hours post-dose on Day 15 of Cycle 1. One cycle=28 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start29 Jan 2018
- Primary completion12 Jul 2027 (estimated)
- Study completion12 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EGFR-mutant Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study chair, Novartis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03333343
- Sponsor's protocol ID
- CEGF816X2102
- Other IDs
- 2024-511757-21-00
- Status last verified
- Nov 2026
- First submitted
- 31 Oct 2017
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03333343
- Acronym / sponsor ID
- CEGF816X2102
- Conditions
- EGFR-mutant Non-small Cell Lung Cancer
- Keywords
- EGFR-mutant NSCLC, EGF816, LXH254, INC280, ribociclib, trametinib, gefitinib, EGFR T790M
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 29 Jan 2018 (actual)
- Primary completion
- 12 Jul 2027 (estimated)
- Study completion
- 12 Jul 2027 (estimated)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: EGF816, Drug: trametinibEGF816+ trametinib in escalation phase |
| Arm 2 | Experimental | Drug: EGF816, Drug: ribociclibEGF816 + ribociclib in escalation phase |
| Arm 3 | Experimental | Drug: EGF816, Drug: LXH254EGF816 + LXH254 in escalation phase |
| Arm A | Experimental | Drug: EGF816, Drug: INC280EGF816 + INC280 in expansion phase (patients with no known resistance mechanism) |
| Arm B | Experimental | Drug: EGF816, Drug: trametinibEGF816 + trametinib in expansion phase |
| Arm C | Experimental | Drug: EGF816, Drug: ribociclibEGF816 + ribociclib in expansion phase |
| Arm D | Experimental | Drug: EGF816, Drug: LXH254EGF816 + LXH254 in expansion phase (patients with no known resistance mechanism) |
| Arm E | Experimental | Drug: EGF816, Drug: LXH254EGF816 + LXH254 in expansion phase (patients with known resistance mechanism) |
| Arm F | Experimental | Drug: EGF816, Drug: gefitinibEGF816 + gefitinib in expansion phase |
| Arm G | Experimental | Drug: EGF816, Drug: INC280EGF816 + INC280 in expansion phase (patients with known resistance mechanism) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EGF816Study Drug | Drug | Arm 1, Arm 2, Arm 3, Arm A, Arm B, Arm C, Arm D, Arm E, Arm F, Arm G |
| trametinibStudy Drug | Drug | Arm 1, Arm B |
| ribociclibStudy Drug | Drug | Arm 2, Arm C |
| LXH254Study Drug | Drug | Arm 3, Arm D, Arm E |
| INC280Study Drug | Drug | Arm A, Arm G |
| gefitinibStudy Drug | Drug | Arm F |
Primary outcome
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.
Number of participants with DLTs in the first cycle of combination (Dose escalation only)
Time frame: 28 days
A Dose-Limiting Toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications that occurs within the first 28 days of combination treatment during the dose escalation part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Number of participants with dose interruptions and reductions
Time frame: From first dose until study ends, approximately 4 years
Assessment of tolerability. For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments may be permitted in order to allow patients to continue the study treatment.
Dose intensity of study drugs
Time frame: From first dose until study ends, approximately 4 years
Dose intensity is computed as the ratio of actual cumulative dose received to actual duration of exposure.
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)
7 secondary outcomes
ORR
Time frame: Every 8-12 weeks until study ends, approximately 4 years
PFS
Time frame: Every 8-12 weeks until study ends, approximately 4 years
DCR
Time frame: Every 8-12 weeks until study ends, approximately 4 years
DOR
Time frame: Every 8-12 weeks until study ends, approximately 4 years
Time to response
Time frame: Every 8-12 weeks until study ends, approximately 4 years
Area under the plasma concentration-time curve (AUC) of study drugs
Time frame: From pre-dose up to 8 hours post-dose on Day 15 of Cycle 1. One cycle=28 days.
Maximum observed plasma concentration (Cmax) of study drugs
Time frame: From pre-dose up to 8 hours post-dose on Day 15 of Cycle 1. One cycle=28 days.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study chair
Novartis
11 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EGF816, trametinib and ribociclib in people with EGFR-mutant Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 11 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Italy, Germany, Singapore, Taiwan, Canada and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with adverse events and serious adverse events (time frame: Every day until study end, approximately 4 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.