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AzTrials

Metastatic Lung Non-Small Cell CarcinomaPhase 1NCT04780568

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

A Phase 1 study testing Osimertinib, Tegavivint and Echocardiography Test in people with Metastatic Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Osimertinib, Tegavivint and Echocardiography Test
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
18 Jan 2022to 31 Jul 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%)
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  • 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
  • If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
  • If history of hepatitis C virus (HCV) infection, it must be treated and have an undetectable viral load
  • Patients with treated brain metastases are asymptomatic and not requiring ongoing treatment
  • Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS)-specific treatment is not required and is unlikely to be required during the first cycle of therapy. Clinical stability on a stable dose of decadron is permitted
  • Patients with a prior or concurrent malignancy whose natural history or treatment will not interfere with the safety or efficacy assessment of the investigational drugs are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better
  • Ability to understand and sign a written informed consent document

Who cannot join

  • 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
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  • 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)
  • Patients with active malignancies other than NSCLC or patients with prior curatively treated malignancy at high risk of relapse during the study period with the exception of localized squamous or basal cell skin cancers, ductal carcinoma in-situ (DCIS), or indolent cancer currently on observation (i.e. chronic lymphocytic leukemia [CLL] or low-risk prostate cancer)
  • Any evidence of severe or uncontrolled systemic disease, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection with human immunodeficiency virus (HIV). Screening for chronic conditions is not required
  • Patients who are at risk for impaired absorption of oral medication including, but not limited to, refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9291
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, or requirements
  • Involvement in the planning and/or conduct of the study (applies to both investigator staff and/or staff at the study site)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

The Ohio State University Comprehensive Cancer Center contact

800-293-5066

OSUCCCClinicaltrials@osumc.edu

United States1 site, 1 recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Regan M. Memmott, M.D., Ph.D, 614-366-1618, regan.memmott@osumc.edu

    Regan M. Memmott, M.D., Ph.D

    Recruiting

Other trials in United States

About this study

Official title: 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)

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

  1. 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.

Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OsimertinibDrug

    Also called AZD-9291, AZD9291, Mereletinib, Tagrisso

    Given PO

  • TegavivintDrug

    Also called BC 2059, BC-2059, BC2059, Tegatrabetan

    Given IV

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography, ECHO

    Undergo ECHO

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA scan

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT scan, Computed Axial Tomography, computerized axial tomography

    Undergo CT

  • FDG-Positron Emission TomographyProcedure or surgery

    Also called FDG, FDG-PET, FDG-PET Imaging

    Undergo 18F-FDG PET

  • Biospecimen CollectionProcedure or surgery

    Also called Biological sample collection, Biospecimen collected, Specimen Collection

    Undergo blood and/or tissue sample collection

Study groups in NCT04780568
Study groupRoleWhat they receive
Treatment (osimertinib, tegavivint)ExperimentalPatients 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.
Receives: Drug: Osimertinib; Drug: Tegavivint; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Computed Tomography; Procedure: FDG-Positron Emission Tomography; Procedure: Biospecimen Collection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose

    Measured: Up to 28 days

Secondary outcomes (4)

  1. Overall response rate (ORR)

    Defined as patients with complete or partial response using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. will be calculated as the proportion of patients who achieve a response to therapy divided by the total number of evaluable patients. An evaluable patient is defined as an eligible patient who has received at least one dose of therapy. All evaluable patients will be included in calculating the ORR for the study along with corresponding 95% binomial confidence intervals (CIs) (assuming that the number of patients who respond is binomially distributed).

    Measured: Up to 4 years

  2. Progression free survival

    Survival will initially be modeled using Kaplan-Meier methods, resulting in median survival times with 95% CI, assuming sufficient events have occurred.

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

  3. Duration of response

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

  4. Overall survival

    Survival will initially be modeled using Kaplan-Meier methods, resulting in median survival times with 95% CI, assuming sufficient events have occurred.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2021
  2. Study start18 Jan 2022
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Jul 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04780568
Sponsor's protocol ID
OSU-20298
Other IDs
NCI-2021-01360
Status last verified
Sep 2026
First submitted
28 Feb 2021
Last updated
15 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Osimertinib, Tegavivint and Echocardiography Test in people with Metastatic Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact The Ohio State University Comprehensive Cancer Center (800-293-5066, OSUCCCClinicaltrials@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04780568.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.

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