EGFR Gene Mutation, Lung Cancer, Lung Cancer Metastatic
Conditions
Keywords
EGFR C797S, EGFR mutant lung cancer, dacomitinib, osimertinib, 18-341, Memorial Sloan Kettering Cancer Center
Brief summary
The purpose of this study is to assess whether dacomitinib after osimertinib is effective in participants with metastatic EGR-mutant lung cancers.
Interventions
DRUGDacomitinib
Cohort 1 Dacomitinib Dosing: Dose level 1: Dacomitinib 45mg daily Dose level -1: Dacomitinib 30mg daily Dose level -2: Dacomitinib 15mg daily Cohort 2 Dacomitinib Dosing: Dose level 1: Dacomitinib 30 mg daily Dose level -1: Dacomitinib 15 mg daily
DRUGOsimertinib
In cohort 2, participants will begin on dacomitinib orally daily in combination with Osimertinib Dose level Osimertinib Dosing: Dose level 1: Osimertinib 80 mg daily Dose level -1: Osimertinib 40 mg daily
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Advanced biopsy-proven metastatic non-small cell lung cancer * Somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy * Prior treatment with osimertinib with response followed by disease progression * No prior first or second generation EGFR inhibitor treatment (gefitinib, afatinib, erlotinib) * Archival tissue available from a tumor biopsy done after disease progression on osimertinib or willing to undergo a tumor biopsy or liquid biopsy after disease progression on osimertinib prior to study initiation * Measurable (RECIST 1.1) indicator lesion not previously irradiated * Karnofsky performance status (KPS) \>/= 70% * Age \>/= 18 years old * Ability to swallow oral medication * Adequate organ function * AST, ALT \</= 3 x ULN * Total bilirubin \</= 1.5x ULN * Creatinine \</= 1.5x ULN OR calculated creatinine clearance \>/= 60ml/min * Absolute neutrophil count (ANC) \>/= 1000 cells/mm3 * Hemoglobin\>/=8.0 g/dL * Platelets \>/=75,000/mm3
Exclusion criteria
* Pregnant or lactating women * Any radiotherapy within 1 week of starting treatment on protocol. * Any major surgery within 1 weeks of starting treatment on protocol. * Any evidence of active clinically significant interstitial lung disease * Continue to have unresolved \> grade 1 toxicity from any previous treatment Treatment * Patients with a known mechanism of resistance to osimertinib that will clearly not respond to dacomitinib therapy (i.e. known MET amplification, ALK fusion, RET fusion). * Symptomatic brain metastases or leptomeningeal disease requiring escalating doses of steroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 1 year | Overall response rate (partial and complete responses) of dacomitinib in participants with EGFR-mutant lung cancers and disease progression on osimertinib |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival | 1 year |
| Overall survival | 1 year |
Countries
United States
Outcome results
None listed