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Advanced Lung Non-Small Cell CarcinomaPhase 1/2NCT03831932

Telaglenastat Hydrochloride and Osimertinib in Treating Patients With EGFR-Mutated Stage IV Non-small Cell Lung Cancer

A Phase 1/2 study testing Biospecimen Collection, Computed Tomography and Magnetic Resonance Elastography in people with Advanced Lung Non-Small Cell Carcinoma and Metastatic Lung Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 11 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase Ib trial studies the side effects and best dose of telaglenastat hydrochloride when given together with osimertinib in treating patients with stage IV non-small cell lung cancer and a mutation in the EGFR gene. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Computed Tomography and Magnetic Resonance Elastography
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
11 sitesUnited States
Study dates
16 Mar 2020to 13 Mar 2027
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically confirmed, stage IV NSCLC, with advanced or metastatic disease
  • Activating mutation present in the EGFR gene (L858R or exon 19 deletion, alone or in combination with other EGFR mutations) as per local assessment of a tissue biopsy/cytology specimen. The tissue biopsy must have been obtained since the time of disease progression on most recent targeted therapy. "Liquid" biopsies (i.e. blood based) biopsies cannot be used for eligibility determination
  • Patients must have had progressive disease on prior EGFR inhibitor therapy (gefitinib, erlotinib, afatinib, or osimertinib). There is no limit to lines of prior tyrosine kinase inhibitor (TKI) therapy. Prior osimertinib (AZD9291) therapy is permitted
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Age > 18 years. NSCLC is exceedingly rare in patients < 18 years of age. Because no dosing or adverse event (AE) data are currently available on the use of telaglenastat (CB-839) HCl in combination with osimertinib (AZD9291) in patients < 18 years of age, children are excluded from this study
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
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  • 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 of normal (ULN) and up to 3 mg/dL for patients with Gilbert's disease
  • 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
  • Should participants with hepatitis B virus (HBV) infection be included, patients are only eligible if they meet all the following criteria:
  • Demonstrated absence of hepatitis C virus (HCV) co-infection or history of HCV co-infection
  • Demonstrated absence of human immunodeficiency virus (HIV) infection
  • Participants with active HBV infection are eligible if they are:
  • Receiving anti-viral treatment for at least 6 weeks prior to study treatment, HBV DNA is suppressed to <100 IU/mL and transaminase levels are below ULN. Participants with a resolved or chronic infection HBV are eligible if they are:
  • Negative for hepatitis B surface antigen (HBsAg) and positive for hepatitis B core antibody [anti-HBc IgG]. In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment and 6-12 months (To be determined [TBD] by hepatologist) post treatment OR
  • Positive for HBsAg, but for > 6 months have had transaminases levels below ULN and HBV DNA levels below <100 IU/mL (i.e., are in an inactive carrier state). In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment and 6-12 months (TBD by hepatologist) post treatment
  • If history of hepatitis C virus (HCV) infection, must be treated and have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS) - directed therapy shows no evidence of progression
  • Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy. Patients on corticosteroids for the treatment of brain metastases will be permitted as long as the dose is =< 10 mg of prednisone-equivalent and has not been increased within 2 weeks of screening
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen 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 should be class 2B or better
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
  • EXPANSION COHORT: Patients must have had progressive disease on prior first line EGFR inhibitor therapy with osimertinib

Who cannot join

  • Patients who have not recovered from AEs due to prior systemic anti-cancer therapy (i.e., have residual toxicities > grade 1), with the exception of alopecia. Note: Subjects with irreversible toxicity that in the opinion of the treating physician is not reasonably expected to be exacerbated by the investigational treatment may be included (e.g., hearing loss, hormone deficiency requiring replacement therapy)
  • Previous enrollment in the present study
  • 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 within five half-lives of the compound or 3 months, whichever is greater. Patients who have received prior immunotherapy may be included only if time from last immunotherapy is at least 3 months (i.e. 90 days)
  • Spinal cord compression, symptomatic and unstable brain metastases except for those patients who have completed definitive therapy, and have had a stable neurological status for at least 2 weeks after completion of definitive therapy. Patients may be on corticosteroids (=< 10 mg of prednisone-equivalent) to control brain metastases if they have been on a stable dose for 2 weeks (14 days) prior to the start of study treatment and are clinically asymptomatic
  • Patients with an uncontrolled intercurrent illness
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  • 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 to telaglenastat (CB-839) HCl, osimertinib (AZD9291), or other agents used in study. Patients with hypersensitivity to to any of the inactive excipients thereof 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 telaglenastat (CB-839) HCl is a glutaminase inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with telaglenastat (CB-839) HCl and osimertinib (AZD9291), breastfeeding should be discontinued if the mother is treated with telaglenastat (CB-839) HCl and osimertinib (AZD9291). Breastfeeding patients will be excluded. These potential risks may also apply to other agents used in this study
  • 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 (QTc using Fridericia's formula [QTcF]) > 470 msec (Fridericia's Criteria for Corrected QT interval [QTc] Calculation: Fridericia's formula QTcF = (QT/RR 0.33). 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 electrocardiogram (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 heart failure, electrolyte abnormalities (including: Serum/plasma potassium < lower limit of normal (LLN); serum/plasma magnesium < LLN; serum/plasma calcium < LLN , 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 and cause Torsades de Pointes
  • 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 diseases, 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 with symptomatic CNS metastases who are neurologically unstable
  • 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 telaglenastat (CB-839) HCl and osimertinib (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 and 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

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

Other trials in United States

About this study

Official title: A Phase Ib Study of Osimertinib (AZD9291) and Telaglenastat (CB-839) HCl in Patients With EGFR Mutant Non-Small Cell Lung Cancer

This phase Ib trial studies the side effects and best dose of telaglenastat hydrochloride when given together with osimertinib in treating patients with stage IV non-small cell lung cancer and a mutation in the EGFR gene. Telaglenastat hydrochloride and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVE:

I.To assess the safety and tolerability of osimertinib (AZD9291) and telaglenastat (CB-839) hydrochloride (HCl) and determine the recommended phase II dose (RP2D) in patients with metastatic, EGFR activating mutation-positive non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

  1. To determine toxicity profile of the combination of osimertinib (AZD9291) and telaglenastat (CB-839) HCl in patients with metastatic EGFR activating mutation positive NSCLC.

II. To assess the pharmacokinetics (PK) of telaglenastat (CB-839) HCl and osimertinib (AZD9291) in patients with metastatic EGFR activating mutation positive NSCLC.

EXPLORATORY/CORRELATIVE OBJECTIVES:

  1. To determine the progression free survival (PFS) of osimertinib (AZD9291) and telaglenastat (CB-839) HCl in patients with EGFR mutation positive NSCLC who have developed progressive disease (PD) on front-line EGFR inhibitor therapy.

II. To determine the overall survival (OS) of osimertinib (AZD9291) and telaglenastat (CB-839) HCl in patients with EGFR mutation positive NSCLC who have developed PD on front-line EGFR inhibitor therapy.

III. To assess cell-free deoxyribonucleic acid (DNA) (cfDNA) and measure changes with response to treatment as well as disease progression (EGFR sensitizing mutations, T790M resistance mutation, recognized bypass mechanisms).

IV. To assess circulating levels of glutamine, glutamate, aspartate and asparagine, and measure changes with response to treatment as well as disease progression.

  1. To assess 18F-fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET) parameters at baseline and after treatment to evaluate changes with response to treatment as well as emergence of disease resistance or progression. (Expansion cohort, select patients only)

VI. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES) and ribonucleic acid (RNA) sequencing (RNAseq), in order to:

VIa. To identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned.

VIb. To identify resistance mechanisms using genomic DNA- and RNA-based assessment platforms.

OUTLINE: This is a phase I, dose-escalation study of telaglenastat hydrochloride followed by a dose-expansion study.

Patients receive telaglenastat hydrochloride orally (PO) twice daily (BID) and osimertinib PO once daily (QD) (starting cycle 1 day 16 of phase I). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and may undergo x-ray imaging, computed tomography (CT) scan, magnetic resonance imaging (MRI), or positron emission tomography (PET) scan throughout the study.

After completion of study treatment, patients are followed up at 30 days.

Being tested
Biospecimen Collection, Computed Tomography, Magnetic Resonance Elastography, Osimertinib, Positron Emission Tomography
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.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Magnetic Resonance ElastographyProcedure or surgery

    Also called MRE

    Undergo MRI

  • OsimertinibDrug

    Also called AZD 9291, AZD-9291, AZD9291, Mereletinib

    Given PO

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET scan

  • Telaglenastat HydrochlorideDrug

    Also called CB-839 HCl, Glutaminase Inhibitor CB-839 Hydrochloride

    Given PO

  • X-Ray ImagingProcedure or surgery

    Also called Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs

    Undergo x-ray imaging

Study groups in NCT03831932
Study groupRoleWhat they receive
Treatment (telaglenastat HCl, osimertinib)ExperimentalPatients receive telaglenastat hydrochloride PO BID and osimertinib PO QD (starting cycle 1 day 16 of phase I). Patients undergo blood sample collection and may undergo x-ray imaging, CT scan, MRI, or PET scan throughout the study. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Elastography; Drug: Osimertinib; Procedure: Positron Emission Tomography; Drug: Telaglenastat Hydrochloride; Procedure: X-Ray Imaging

What is being measured

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

  1. Recommended Phase II Dose (RP2D)

    Measured: Up to 28 days

Secondary outcomes (3)

  1. Dose Limiting Toxicities (DLT)

    Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

    Measured: Up to 28 days

  2. Progression-free Survival (PFS)

    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 documented progression or death without progression, assessed up to 30 days after completion of therapy

  3. Overall Survival (OS)

    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 death from any cause, assessed up to 30 days after completion of therapy

Timeline

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

  1. First posted6 Feb 2019
  2. Study start16 Mar 2020
  3. Primary completion12 Jun 2024
  4. Study completion13 Mar 2027 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03831932
Sponsor's protocol ID
NCI-2019-00572
Other IDs
NCI-2019-00572, OSU 19016, 10216, 10216, UM1CA186712
Status last verified
Sep 2026
First submitted
5 Feb 2019
Last updated
16 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Biospecimen Collection, Computed Tomography and Magnetic Resonance Elastography in people with Advanced Lung Non-Small Cell Carcinoma and Metastatic Lung Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 11 sites 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 30 inclusion and 22 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: under way, not looking for participants, as of the sponsor's last update on 16 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 11 sites 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended Phase II Dose (RP2D) (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 NCT03831932.

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 16 Sep 2026.

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