Dacomitinib and Osimertinib in Treating Patients with Metastatic EGFR Mutant Non-small Cell Lung Cancer
This phase I trial studies the side effects and best dose of dacomitinib and osimertinib in treating patients with EGFR mutant non-small cell lung cancer that has spread to other places in the body. Dacomitinib and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Inclusion Criteria
- Written informed consent
- Advanced biopsy-proven metastatic non-small cell lung cancer
- Somatic activating mutation in EGFR in a tumor biopsy
- No prior EGFR inhibitor treatment (gefitinib, afatinib, erlotinib, dacomitinib, osimertinib) however, prior treatment with other chemotherapies are allowed
- Archival tissue available from a pre-treatment tumor biopsy or willing to undergo a tumor biopsy prior to study initiation
- Measurable (RECIST 1.1) indicator lesion not previously irradiated
- Karnofsky performance status (KPS) >= 70%
- Ability to swallow oral medication
- Agree to use effective methods of contraception from the time of screening until 3 months after treatment discontinuation (for males and females of child-bearing potential)
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 x upper limits of normal (ULN)
- Total bilirubin =< 1.5 x ULN
- Creatinine =< 1.5 x ULN OR calculated creatinine clearance >= 60 ml/min
- Absolute neutrophil count (ANC) >= 1000 cells/mm^3
- Hemoglobin >= 9.0 g/dL
- Platelets >= 100,000/mm^3
Exclusion Criteria
- Pregnant or lactating women
- Any radiotherapy within 1 week of starting treatment on protocol
- Any major surgery within 1 week of starting treatment on protocol
- Any evidence of active clinically significant interstitial lung disease
- A mean corrected QT (QTc) > 470 ms (Fridericia's correction), clinically important arrhythmia, conduction or morphology of resting electrocardiography (ECG) (e.g. complete left bundle branch block [LBBB], 1st-3rd degree heart block, any factors that increase the risk of QTc prolongation or risk of arrhythmia)
- Cardiovascular disease or cerebrovascular disease, cerebrovascular accident (CVA) or myocardial infarction (MI) < 6 months prior to study enrollment, unstable angina, NYHA > grade II congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or with the potential to interfere with protocol treatment
- History of pneumonitis or interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis that required steroid treatment, and any evidence of clinically active ILD
- Serious chronic gastrointestinal (GI) conditions associated with diarrhea
- Symptomatic, unstable brain metastases requiring escalating doses of steroids
- Continue to have unresolved > Common Terminology Criteria for Adverse Events (CTCAE) grade 1 toxicity from any previous treatment
Additional locations may be listed on ClinicalTrials.gov for NCT03810807.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To determine maximum tolerated dose of the combination of dacomitinib and osimertinib in patients with EGFR mutated advanced non-small cell lung cancer (NSCLC). (Phase 1 Escalation Cohort)
II. To further establish the toxicity profile of the combination of combination dacomitinib and osimertinib. (Phase 1 Expansion Cohort)
SECONDARY OBJECTIVES:
I. Measure best overall response. (Phase 1 Escalation Cohort)
II. Measure progression-free survival (PFS). (Phase 1 Escalation Cohort)
III. Measure overall survival (OS). (Phase 1 Escalation Cohort)
IV. Determine the frequency of EGFR T790M and C797S emergence on this combination regimen. (Phase 1 Escalation Cohort)
V. To obtain preliminary efficacy data by measuring the objective response rate (sum of complete responses and partial responses according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1), progression free survival and overall survival. (Phase 1 Expansion Cohort)
CORRELATIVE STUDIES OBJECTIVES:
I. Identify any pre-treatment biomarkers that predict response to combination osimertinib/dacomitinib in this setting.
II. Identify molecular biomarkers within plasma (sensitizing EGFR mutation, EGFR C797S, EGFR T790M), quantify and follow serially over time.
III. Determine the mechanisms of resistance to osimertinib/dacomitinib treatment.
OUTLINE: This is a dose-escalation study of dacomitinib and osimertinib.
Patients receive dacomitinib orally (PO) once daily (QD) and osimertinib PO QD or twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorHelena A. Yu
- Primary ID18-411
- Secondary IDsNCI-2019-00499
- ClinicalTrials.gov IDNCT03810807