Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC
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ClinicalTrials.gov Identifier: NCT03333343 |
Recruitment Status :
Active, not recruiting
First Posted : November 6, 2017
Last Update Posted : June 30, 2022
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Condition or disease | Intervention/treatment | Phase |
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EGFR-mutant Non-small Cell Lung Cancer | Drug: EGF816 Drug: trametinib Drug: ribociclib Drug: LXH254 Drug: INC280 Drug: gefitinib | Phase 1 |
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 : | Interventional (Clinical Trial) |
Actual Enrollment : | 105 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 : | September 8, 2023 |
Estimated Study Completion Date : | September 10, 2023 |

Arm | Intervention/treatment |
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Experimental: Arm 1
EGF816+ trametinib in escalation phase
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Drug: EGF816
Study Drug Drug: trametinib Study Drug |
Experimental: Arm 2
EGF816 + ribociclib in escalation phase
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Drug: EGF816
Study Drug Drug: ribociclib Study Drug |
Experimental: Arm 3
EGF816 + LXH254 in escalation phase
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Drug: EGF816
Study Drug Drug: LXH254 Study Drug |
Experimental: Arm A
EGF816 + INC280 in expansion phase (patients with no known resistance mechanism)
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Drug: EGF816
Study Drug Drug: INC280 Study Drug |
Experimental: Arm B
EGF816 + trametinib in expansion phase
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Drug: EGF816
Study Drug Drug: trametinib Study Drug |
Experimental: Arm C
EGF816 + ribociclib in expansion phase
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Drug: EGF816
Study Drug Drug: ribociclib Study Drug |
Experimental: Arm D
EGF816 + LXH254 in expansion phase (patients with no known resistance mechanism)
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Drug: EGF816
Study Drug Drug: LXH254 Study Drug |
Experimental: Arm E
EGF816 + LXH254 in expansion phase (patients with known resistance mechanism)
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Drug: EGF816
Study Drug Drug: LXH254 Study Drug |
Experimental: Arm F
EGF816 + gefitinib in expansion phase
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Drug: EGF816
Study Drug Drug: gefitinib Study Drug |
Experimental: Arm G
EGF816 + INC280 in expansion phase (patients with known resistance mechanism)
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Drug: EGF816
Study Drug Drug: INC280 Study Drug |
- 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)
- 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 ]

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.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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).
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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

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
Canada, Ontario | |
Novartis Investigative Site | |
Toronto, Ontario, Canada, M5G 2M9 | |
Germany | |
Novartis Investigative Site | |
Essen, Germany, 45147 | |
Novartis Investigative Site | |
Koeln, Germany, 50937 | |
Hong Kong | |
Novartis Investigative Site | |
Shatin, New Territories, Hong Kong | |
Italy | |
Novartis Investigative Site | |
Ancona, AN, Italy, 60126 | |
Novartis Investigative Site | |
Milano, MI, Italy, 20162 | |
Novartis Investigative Site | |
Rozzano, MI, Italy, 20089 | |
Singapore | |
Novartis Investigative Site | |
Singapore, Singapore, 119228 | |
Novartis Investigative Site | |
Singapore, Singapore, 169610 | |
Taiwan | |
Novartis Investigative Site | |
Tainan, Taiwan, 70403 | |
Novartis Investigative Site | |
Taipei, Taiwan, 10002 |
Study Chair: | Novartis Pharmaceuticals | Novartis |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT03333343 |
Other Study ID Numbers: |
CEGF816X2102 2017-002496-25 ( EudraCT Number ) |
First Posted: | November 6, 2017 Key Record Dates |
Last Update Posted: | June 30, 2022 |
Last Verified: | June 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
EGFR-mutant NSCLC EGF816 LXH254 INC280 ribociclib trametinib |
gefitinib EGFR T790M BRAF mutation BRAF fusion BRAF rearrangement MET amplification |
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 Nazartinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |