This phase I trial tests the safety, side effects, and best dose of osimertinib, cetuximab, and tucatinib in treating patients with EFGR-mutant non-small cell lung cancer that is stage IV or has come back (recurrent). Osimertinib and tucatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Cetuximab is a chimeric human/mouse IgG1 monoclonal antibody that targets epidermal growth factor receptor (EGFR), a receptor overexpressed in many types of cancer, and may interfere with the ability of tumor cells to grow and spread. Giving osimertinib, cetuximab, and tucatinib may work better in treating patients with non-small cell lung cancer.
Participants with Stage IV or recurrent/metastatic histologically confirmed non-small cell lung cancer (NSCLC).
NSCLC must harbor at least one of the following EGFR activating mutations: Exon 21 L858R, Exon 19 deletion, Exon 18 G719X, Exon 21 L861Q, Exon 20 S768I.
For patients in the dose escalation cohort, patients must have progressed on any prior EGFR-Tyrosine Kinase Inhibitor (TKI) and if T790M positive must have also progressed on osimertinib. Participants in the dose expansion cohort must have had progressive disease as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version (v)1.1 criteria on osimertinib as first-line therapy.
4. Participants in the dose expansion cohort must be negative for clinically significant non-ERBB bypass tract resistance such as MET amplification, BRAF mutation, RAS-RAF-MAPK alteration, ALK fusion, RET fusion by a Clinical Laboratory Improvement Amendments (CLIA) (performed after progression on prior EGFR-TKI; if any questions please consult with the Principal Investigator). A defined subset of patients in the expansion cohort will have human epidermal growth factor receptor (HER2) aberrant signaling as putative resistance to osimertinib with overexpression/amplification (or more rarely HER2 Exon 20 insertion mutation) as determined by IHC (3+ IHC) or FISH (HER2/CEP17 > 2.2 or HER2 copy number > 6) or NGS for HER2 mutation.
History of pneumonitis requiring steroids, including history of radiation-induced pneumonitis.
Known or suspected leptomeningeal disease as documented by the investigator. Stable asymptomatic brain metastases not requiring steroids is allowed; radiation for brain metastases is allowed as long as there is a two-week washout period prior to starting study treatment.
Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases notwithstanding central nervous system (CNS)-directed therapy.
The participant has a known allergy / history of hypersensitivity reaction to any of the treatment components (including any ingredient or similar ingredient used in the product formulations) or red meat.
Single group
Cetuximab
Biological/VaccineGiven IV
Osimertinib
DrugGiven PO
Tucatinib
DrugGiven PO
Dose-limiting toxicity
The occurrence of a dose-limiting toxicity in participants receiving the combination of osimertinib, cetuximab, and tucatinib.
Incidence of adverse events
Number of participants experiencing adverse events (AEs), both non treatment related and treatment related, classified by severity and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
Objective response rate (ORR)
Objective response rate (ORR), assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria.
Progression-free survival (PFS)
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Jonathan Riess
Lead sponsor
University of California, Davis
Sponsor institution
National Cancer Institute (NCI)
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
