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

NCT03831932 | Active Not Recruiting Phase 1 Results FDA Drug

• 4 other identifiers: NCI-2019-00572OSU 1901610216UM1CA186712
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 11

Brief 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. Telaglenastat hydrochloride and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Recommended Phase II Dose (RP2D)

  Up to 28 days

Secondary Outcomes (3)

• Dose Limiting Toxicities (DLT)

  Up to 28 days

• Progression-free Survival (PFS)

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

• Overall Survival (OS)

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

Other Outcomes (5)

• Post-glutaminase Inhibitor CB-839 Hydrochloride Pharmacokinetics (PK) (CB-839 HCl)

  Day 15 of cycle 1, day 2 of cycle 2 and day 1 of each subsequent cycle (each cycle = 28 days)

• Post-AZD9291 Pharmacokinetics

  Day 2 of cycle 2 and day 1 of each subsequent cycle (each cycle = 28 days)

• Change in EGFR Mutational Status

  Baseline up to disease progression, assessed up to 30 days after completion of therapy

Study Arms (1)

Treatment (telaglenastat HCl, osimertinib)

EXPERIMENTAL

Patients 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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Elastography; Drug: Osimertinib; Procedure: Positron Emission Tomography; Drug: Telaglenastat Hydrochloride; Procedure: X-Ray Imaging

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (telaglenastat HCl, osimertinib)

Magnetic Resonance Elastography PROCEDURE

Undergo MRI

Also known as: MRE

Treatment (telaglenastat HCl, osimertinib)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (telaglenastat HCl, osimertinib)

Telaglenastat Hydrochloride DRUG

Given PO

Also known as: CB-839 HCl, Glutaminase Inhibitor CB-839 Hydrochloride

Treatment (telaglenastat HCl, osimertinib)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (telaglenastat HCl, osimertinib)

Osimertinib DRUG

Given PO

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

Treatment (telaglenastat HCl, osimertinib)

X-Ray Imaging PROCEDURE

Undergo x-ray imaging

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray, X-Ray

Treatment (telaglenastat HCl, osimertinib)

Eligibility Criteria

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

You may qualify if:

• 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%)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

Location

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Specimen Handling; osimertinib; Magnetic Resonance Spectroscopy; X-Rays; Phantoms, Imaging

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; Spectrum Analysis; Chemistry Techniques, Analytical; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies

Results Point of Contact

• Title: Dr. Dwight Owen
• Organization: The Ohio State University Comprehensive Cancer Center

Dwight.Owen@osumc.edu

614-685-2039

Study Officials

• Dwight H Owen

  Ohio State University Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2019
• First Posted: February 6, 2019
• Study Start: March 16, 2020
• Primary Completion: June 12, 2024
• Study Completion (Estimated): March 13, 2027
• Last Updated: April 13, 2026
• Results First Posted: June 19, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (11)