Ignite Creation Date:
2025-12-24 @ 9:57 PM
Ignite Modification Date:
2026-01-02 @ 6:45 AM
Study NCT ID:
NCT03831932
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-09-19
First Post:
2019-02-05
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Telaglenastat Hydrochloride and Osimertinib in Treating Patients With EGFR-Mutated Stage IV Non-small Cell Lung Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase Ib Study of Osimertinib (AZD9291) and Telaglenastat (CB-839) HCl in Patients With EGFR Mutant Non-Small Cell Lung Cancer
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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:
I. 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:
I. 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.
V. 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.
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:
I. 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:
I. 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.
V. 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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: