Osimertinib and Tegavivint as First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer

NCT04780568 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-20298NCI-2021-01360
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Metastatic Lung Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  Up to 28 days

Secondary Outcomes (4)

• Overall response rate (ORR)

  Up to 4 years

• Progression free survival

  From initiation of therapy to disease progression or death, assessed up to 4 years

• Duration of response

  From objective response to disease progression or death, assessed up to 4 years

• Overall survival

  From start of treatment until death of any cause, assessed up to 4 years

Other Outcomes (5)

• Tegavivint (BC2059) pharmacokinetics (PK)

  On days 1, 2, 5, 8, 15, 16, 19, and 22 of cycle 1 (each cycle is 28 days)

• Osimertinib (AZD9291) PK

  On days 1, 2, 8, 15, 16, and 22 of cycle 1 (each cycle is 28 days)

• Β-catenin pathway activity

  Up to 4 years

Study Arms (1)

Treatment (osimertinib, tegavivint)

EXPERIMENTAL

Patients receive osimertinib PO QD on days 1-28 and tegavivint IV on day 1. Treatment repeats 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. Treatment repeats every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Osimertinib; Drug: Tegavivint; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Computed Tomography; Procedure: FDG-Positron Emission Tomography; Procedure: Biospecimen Collection

Interventions

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography, ECHO

Treatment (osimertinib, tegavivint)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide ventriculography, RNV

Treatment (osimertinib, tegavivint)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT scan, Computed Axial Tomography, computerized axial tomography, Computerized Tomography, CT, CT scan, Diagnostic CAT scan

Treatment (osimertinib, tegavivint)

FDG-Positron Emission Tomography PROCEDURE

Undergo 18F-FDG PET

Also known as: FDG, FDG-PET, FDG-PET Imaging

Treatment (osimertinib, tegavivint)

Biospecimen Collection PROCEDURE

Undergo blood and/or tissue sample collection

Also known as: Biological sample collection, Biospecimen collected, Specimen Collection

Treatment (osimertinib, tegavivint)

Tegavivint DRUG

Given IV

Also known as: BC 2059, BC-2059, BC2059, Tegatrabetan

Treatment (osimertinib, tegavivint)

Osimertinib DRUG

Given PO

Also known as: AZD-9291, AZD9291, Mereletinib, Tagrisso

Treatment (osimertinib, tegavivint)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years. Children are excluded from this study because neither dosing nor safety data are currently available for AZD9291 or BC2059 in patients \< 18 years of age
• Pathology-confirmed metastatic NSCLC
• A common activating mutation must be present in the EGFR gene, i.e., exon 19 deletion or L858R. The presence of uncommon EGFR mutations, e.g., G719X, S768I, or L861Q are also permitted if they co-occur with a common activating mutation. Mutation status must be determined using a tumor biopsy by local Clinical Laboratory Improvement Act (CLIA)-certified assessment. Mutations identified by blood-based testing can be provided, but must be verified by tumor biopsy
• The presence of a concurrent T790M mutation, while uncommon in patients who are naïve to treatment with EGFR TKIs, is also permitted
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• The patient must be able to swallow pills
• Life expectancy \> 3 months
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 90 g/L
• Total bilirubin =\< 1.5 x institutional upper limit normal (ULN) and up to 3 mg/dL for patients with Gilbert's
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase ALT (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN and =\< 5 x institutional ULN for patients with liver metastases
• Creatinine within 1.5 x ULN OR glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2 (measured or calculated by Cockcroft and Gault equation) -confirmation of creatinine clearance is only required for patients with creatinine levels above institutional upper limit of normal

You may not qualify if:

• Prior treatment with an EGFR TKI in any setting
• Patients who have not recovered from adverse events (AEs) due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1), with the exception of alopecia
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease
• Patients who are receiving any other investigational agent or immunotherapy within five half-lives of the compound or 3 months, whichever is greater
• Patients with an uncontrolled intercurrent illness
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• History of allergic reactions attributed to compounds of similar chemical or biologic composition as BC2059 or AZD9291. Patients with hypersensitivity to any of the inactive excipients should also be excluded
• Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (wash-out periods vary. All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4
• Pregnant women are excluded from this study because BC2059 has the potential for teratogenic or abortifacient effects. There is also an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with AZD9291 or BC2059. Breastfeeding patients will be excluded
• Patients with a significant history of cardiovascular disease (e.g., myocardial infarction \[MI\], thrombotic or thromboembolic event in the last 6 months)
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (corrected QT \[QTc\] using Fredericia's formula \[QTcF\]) \> 470 msec. RR is the time from the interval of 1 QRS complex to the next measured in seconds and is commonly calculated as (60/HR)
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as decompensated heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to prolong the QT interval
• Left ventricular ejection fraction (LVEF) \< lower limit of normal (LLN) as assessed by either multigated acquisition (MUGA) scan or echocardiogram (ECHO)

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

osimertinib; Specimen Handling

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Regan M Memmott, M.D., Ph.D

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 28, 2021
• First Posted: March 3, 2021
• Study Start: January 18, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2029
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)