NCT06067776

Osimertinib, Cetuximab, and Tucatinib for the Treatment of EGFR-Mutant Stage IV or Recurrent Non-small Lung Cell Cancer

A Phase I Study of Osimertinib, Cetuximab, and Tucatinib in Advanced EGFR-Mutant NSCLC With Acquired Resistance to Osimertinib

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Jonathan Riess · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVE : I. To estimate the maximum tolerated dose (MTD) of osimertinib, cetuximab, and tucatinib in participants with EGFR-mutant non-small cell lung cancer (NSCLC) who have acquired resistance to EGFR-tyrosine kinase inhibitor (TKI). SECONDARY OBJECTIVES: I. To evaluate the toxicities of osimertinib, cetuximab, and tucatinib in participants with EGFR-mutant NSCLC who have acquired resistance to EGFR-TKI. II. To obtain preliminary assessment of anti-tumor activity of osimertinib, cetuximab, and tucatinib in participants with EGFR-mutant NSCLC who have acquired resistance to EGFR-TKI (osimertinib). III. To obtain preliminary assessment of anti-tumor activity of osimertinib, cetuximab, and tucatinib in the dose expansion cohort of participants with EGFR-mutant NSCLC who progressed on first-line osimertinib and do not have non-ERBB bypass tract mechanisms of resistance, including a subset of participants positive for HER2 aberrant signaling as determined by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and/or next generation sequencing (NGS). OUTLINE: This is a dose-escalation study of tucatinib and cetuximab. Patients receive tucatinib 200mg orally BID, osimertinib 80mg orally daily, and cetuximab 250mg/m\^2 IV every 2 weeks of a 28-day cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and every 12 weeks for up to 2 years.

Conditions

• Metastatic Lung Non-Small Cell Carcinoma
• Recurrent Lung Non-Small Cell Carcinoma
• Stage IV Lung Cancer AJCC v8

Interventions

Type	Name	Description
BIOLOGICAL	Cetuximab	Given IV
DRUG	Osimertinib	Given PO
DRUG	Tucatinib	Given PO

Timeline

• Start date: 2024-01-01
• Primary completion: 2025-01-01
• Completion: 2026-11-01
• First posted: 2023-10-05
• Last updated: 2023-10-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study