A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progression on Osimertinib.

Study Overview
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Brief Summary
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The purpose of this study is to assess whether dacomitinib after osimertinib is effective in participants with metastatic EGR-mutant lung cancers.

Official Title
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A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progressionon Osimertinib.

Conditions
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EGFR Gene Mutation, Lung Cancer, Lung Cancer Metastatic

Intervention / Treatment
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* Drug: Dacomitinib
* Drug: Osimertinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Participants treated with dacomitinib alone<br>Participants in this cohort have a somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy. | Drug: Dacomitinib<br>* 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<br>|
| Experimental: Cohort 2: Participants treated with dacomitinib in combination with osimertinib<br>Participants in this cohort have a secondary acquired EGFR mutation in addition to the sensitizing mutation | Drug: Dacomitinib<br>* 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<br>Drug: Osimertinib<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall response rate (partial and complete responses) of dacomitinib in participants with EGFR-mutant lung cancers and disease progression on osimertinib | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 1 year | 
| Overall survival |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EGFR C797S, EGFR mutant lung cancer, dacomitinib, osimertinib, 18-341, Memorial Sloan Kettering Cancer Center