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.
Name: EGF816
Description: Study DrugType: DrugArm 1 Arm 2 Arm 3 Arm A Arm B Arm C Arm D Arm E Arm F Arm G
Name: trametinib
Description: Study DrugType: DrugArm 1 Arm B
Name: ribociclib
Description: Study DrugType: DrugArm 2 Arm C
Name: LXH254
Description: Study DrugType: DrugArm 3 Arm D Arm E
Name: INC280
Description: Study DrugType: DrugArm A Arm G
Name: gefitinib
Description: Study DrugType: DrugArm F
Description: Assess safety and tolerability including incidence of dose limiting toxicities, adverse events, and serious adverse events.
Measure: Number of patients with adverse events and serious adverse events Time: Every day until study end, approximately 4 yearsDescription: Modified objective response rate (ORR2) per RECIST v1.1 (taking as baseline the most recent assessment prior to initiating combination)
Measure: ORR2 Time: Every 8-12 weeks until study ends, approximately 4 yearsDescription: Overall response rate (ORR) per RECIST v1.1
Measure: ORR Time: Every 8-12 weeks until study ends, approximately 4 yearsDescription: 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: PFS Time: Every 8-12 weeks until study ends, approximately 4 yearsDescription: Proportion of patients with best overall response of CR, PR, or SD
Measure: DCR Time: Every 8-12 weeks until study ends, approximately 4 yearsDescription: Time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause
Measure: DOR Time: Every 8-12 weeks until study ends, approximately 4 yearsAllocation: Non-Randomized
Parallel Assignment
There are 2 SNPs
Inclusion Criteria: - Patients must have histologically or cytologically confirmed locally advanced (stage IIIB) or metastatic (stage IV) EGFR mutant (ex19del, L858R) NSCLC. --- L858R ---
- 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. --- L858R ---
- 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. --- T790M --- --- L858R ---
- 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 Inclusion Criteria: - Patients must have histologically or cytologically confirmed locally advanced (stage IIIB) or metastatic (stage IV) EGFR mutant (ex19del, L858R) NSCLC. --- L858R ---
- 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. --- T790M ---
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). --- T790M ---
- 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). --- T790M ---
- 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). --- T790M ---
- 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). --- T790M --- --- T790M ---