NCT03872427

Testing Whether Cancers With Specific Mutations Respond Better to Glutaminase Inhibitor, Telaglenastat Hydrochloride, Anti-Cancer Treatment, BeGIN Study

A Phase II Basket Trial of Glutaminase Inhibitor (BEGIN) Telaglenastat (CB-839) HCL in Patients With NF1 Aberrations, NF1 Mutant Malignant Peripheral Nerve Sheath Tumors (MPNST), KEAP1/NRF2 and LKB1 Aberrant Tumors

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well glutaminase inhibitor telaglenastat hydrochloride (CB-839 HCl) works in treating patients with specific genetic mutations and solid tumors or malignant peripheral nerve sheath tumors that have spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Glutaminase converts an amino acid (building block of proteins) called glutamine to glutamate, which can support several cellular pathways. Telaglenastat hydrochloride works by blocking glutamine activity needed for the growth of cells. When this activity is blocked, the growth of cancer cells may stop and the cancer cells may then die. Cancer is caused by changes (mutations) to genes that control the way cells function and uncontrolled cell growth may result in tumor formation. Specific genetic mutations studied in this clinical trial are NF1 mutation for malignant peripheral nerve sheath tumors, and NF1, KEAP1/NRF2, or STK11/LKB1 mutation for other solid tumors. Telaglenastat hydrochloride 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 best overall response rate (BORR) achieved by 6 months of telaglenastat (CB-839) hydrochloride (HCl) treatment in specific pathway aberrant tumors (MPNST, NF1, KEAP1/NRF2 \& STK11/ LKB1). SECONDARY OBJECTIVES: I. To determine the safety, progression-free survival (PFS), time to progression (TTP) and overall survival (OS). II. To determine the overall response rate (ORR) (highest objective response achieved between start of therapy and progression), time to response (TTR) and clinical benefit rate (CBR) of telaglenastat (CB-839)HCl. III. To assess pharmacodynamic changes and adaptive responses and correlate with response to treatment as well as disease progression (correlative objective). EXPLORATORY OBJECTIVES: I. Correlate fludeoxyglucose F-18 (18-F FDG) positron emission tomography (PET)/computed tomography (CT) pre-therapy and 8-weeks post-therapy response to telaglenastat (CB-839) HCl therapy. II. Evaluate changes in level of circulating tumor deoxyribonucleic acid (DNA) at baseline, one month on-treatment and time of progression (Molecular Characterization Laboratory \[MoCHA Labs\]) to treatment response. III. Quantify the peripheral blood concentrations of the metabolites: aspartate, glutamate, glutamine and arginine (@Mayo clinic Oncometabolomics core) and correlate with response. IV. Evaluate the pharmacodynamic (PD) effect of telaglenastat (CB-839) HCl on systemic levels of the tricarboxylic acid (TCA) cycle metabolites in peripheral blood (baseline and one month) as part of the protocol. V. Evaluate tumor by reverse phase protein array (@core facility at MD Anderson) and ribonucleic acid (RNA) sequencing (seq) to evaluate changes from pre-treatment, during treatment and post treatment specimens. VI. Perform patient-derived tumor xenograft (PDX) modelling-co-clinical trials (@Dr. Funda Meric-Bernstam's lab MD Anderson) to understand response/resistance mechanisms and also evaluate combination therapies for future development. OUTLINE: Patients receive telaglenastat hydrochloride orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, magnetic resonance imaging (MRI), or PET/CT during screening and on study, and collection of blood samples during screening and on study. After completion of study treatment, patients are followed up every 3 months thereafter.

Conditions

• Advanced Malignant Solid Neoplasm
• Metastatic Malignant Solid Neoplasm
• NF1 Mutation Positive Malignant Peripheral Nerve Sheath Tumor
• Unresectable Malignant Solid Neoplasm

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood
PROCEDURE	Computed Tomography	Undergo CT or PET/CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
OTHER	Pharmacodynamic Study	Correlative studies
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
DRUG	Telaglenastat Hydrochloride	Given PO

Timeline

• Start date: 2019-12-14
• Primary completion: 2023-10-30
• Completion: 2026-04-16
• First posted: 2019-03-13
• Last updated: 2025-11-14
• Results posted: 2025-07-01

Locations

31 sites across 1 country: United States

Regulatory

• FDA-regulated drug study