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.
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
Drug | Synonyms | Arms |
---|
EGF816 | | Arm 1 |
trametinib | | Arm 1 |
ribociclib | | Arm 2 |
LXH254 | | Arm 3 |
INC280 | | Arm A |
gefitinib | | Arm 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
Name | Type | Description | Interventions |
---|
Arm 1 | Experimental | EGF816+ trametinib in escalation phase | |
Arm 2 | Experimental | EGF816 + ribociclib in escalation phase | |
Arm 3 | Experimental | EGF816 + LXH254 in escalation phase | |
Arm A | Experimental | EGF816 + INC280 in expansion phase (patients with no known resistance mechanism) | |
Arm B | Experimental | EGF816 + trametinib in expansion phase | |
Arm C | Experimental | EGF816 + ribociclib in expansion phase | |
Arm D | Experimental | EGF816 + LXH254 in expansion phase (patients with no known resistance mechanism) | |
Arm E | Experimental | EGF816 + LXH254 in expansion phase (patients with known resistance mechanism) | |
Arm F | Experimental | EGF816 + gefitinib in expansion phase | |
Arm G | Experimental | EGF816 + INC280 in expansion phase (patients with known resistance mechanism) | |
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: | Active, not 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
June 23, 2021