Trials / Recruiting
RecruitingNCT04780568
Osimertinib and Tegavivint as First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer
A Phase Ib Study of AZD9291 (Osimertinib) and BC2059 (Tegavivint) as First-Line Therapy in Patients With Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)
- Status
- Recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Enrollment
- 24 (estimated)
- Sponsor
- Ohio State University Comprehensive Cancer Center · Academic / Other
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This phase Ib trial is to find out the best dose, possible benefits and/or side effects of osimertinib and tegavivint as first-line therapy in treating patients with EGFR-mutant non-small cell lung cancer that has spread to other places in the body (metastatic). Osimertinib and tegavivint may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVE: I. Assess the safety and tolerability of osimertinib (AZD9291) in combination with tegavivint (BC2059) in patients with metastatic EGFR-mutant non-small lung cancer (NSCLC) and determine the recommended phase 2 dose (RP2D). SECONDARY OBJECTIVES: I. Determine the objective response rate (ORR) in patients with metastatic EGFR-mutant NSCLC treated with the combination of AZD9291 and BC2059. II. Determine the progression free survival (PFS) in patients with metastatic EGFR-mutant NSCLC treated with the combination of AZD9291 and BC2059. III. Determine the duration of response (DOR) in patients with metastatic EGFR-mutant NSCLC treated with the combination of AZD9291 and BC2059. IV. Determine the overall survival (OS) in patients with metastatic EGFR-mutant NSCLC treated with the combination of AZD9291 and BC2059. CORRELATIVE/EXPLORATORY OBJECTIVES: I. Evaluate biomarkers of EGFR, Notch3, and beta-catenin pathway activity in tumor biopsies and blood samples. II. Assess the pharmacokinetics (PK) of AZD9291 and BC2059 in patients with metastatic EGFR-mutant NSCLC. III. Assess circulating tumor deoxyribonucleic acid (DNA) (ctDNA) at baseline, following 2 and 4 weeks of treatment to evaluate for clearance, and at time of progression to assess for changes in EGFR mutation status. IV. Measure response using computed tomography (CT) tumor volumetry and dynamic positron emission tomography (PET)/CT. V. Identify a gene signature that may be predictive of treatment response or resistance using ribonucleic acid (RNA) sequencing of tumor tissue. OUTLINE: Patients receive osimertinib orally (PO) once daily (QD) on days 1-28 of each cycle and tegavivint intravenously (IV) over 4 hours on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive osimertinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition (MUGA) scan, CT, fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET), and blood sample collection throughout the trial. Patients may also undergo tissue sample collection on study. After completion of study treatment, patients are followed up for 30 or 90 days and then every 12 weeks for 4 years.
Conditions
- Metastatic Lung Non-Small Cell Carcinoma
- Stage IV Lung Cancer AJCC v8
- Stage IVA Lung Cancer AJCC v8
- Stage IVB Lung Cancer AJCC v8
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Osimertinib | Given PO |
| DRUG | Tegavivint | Given IV |
| PROCEDURE | Echocardiography Test | Undergo ECHO |
| PROCEDURE | Multigated Acquisition Scan | Undergo MUGA scan |
| PROCEDURE | Computed Tomography | Undergo CT |
| PROCEDURE | FDG-Positron Emission Tomography | Undergo 18F-FDG PET |
| PROCEDURE | Biospecimen Collection | Undergo blood and/or tissue sample collection |
Timeline
- Start date
- 2022-01-18
- Primary completion
- 2026-07-31
- Completion
- 2029-07-31
- First posted
- 2021-03-03
- Last updated
- 2025-12-09
Locations
1 site across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT04780568. Inclusion in this directory is not an endorsement.