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

Plain English Summary

Telaglenastat Hydrochloride and Osimertinib in Treating Patients With EGFR-Mutated Stage IV Non-small Cell Lung Cancer is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8. This trial tests a combination of two drugs, osimertinib and telaglenastat, to see if they are safe and effective for treating a specific type of advanced lung cancer. It is for patients with stage IV non-small cell lung cancer (NSCLC) that has a specific genetic mutation (EGFR). Participation involves taking both drugs and undergoing regular medical check-ups, including scans and blood tests. Alternative treatments may include other targeted therapies or chemotherapy, depending on the patient's specific situation and prior treatments. The trial aims to enroll 22 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults (over 18 years old) with stage IV NSCLC that has progressed after prior EGFR inhibitor treatment. Patients must have a confirmed EGFR gene mutation (L858R or exon 19 deletion) and measurable disease. Individuals with certain pre-existing conditions, such as uncontrolled hepatitis B or active brain metastases, may not be eligible. Patients must have adequate blood counts and organ function (kidney, liver). This trial is studying Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will help determine the safest dose of the new drug combination for future studies. The specific primary outcome measures are: Recommended Phase II Dose (RP2D) (Up to 28 days). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a need for new treatment options for patients with EGFR-mutated lung cancer whose disease has progressed on existing therapies. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

This trial explores a novel combination therapy for a significant subset of lung cancer patients, potentially expanding treatment options and market share for EGFR-targeted therapies. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of participating in this trial. Understand what the study involves, including the schedule of visits, tests, and potential side effects. Be prepared for regular appointments for drug administration, monitoring, and assessments of your cancer's response. The trial is being conducted at 11 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 22 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• PROCEDURE: Computed Tomography — Undergo CT scan
• PROCEDURE: Magnetic Resonance Elastography — Undergo MRI
• DRUG: Osimertinib — Given PO
• PROCEDURE: Positron Emission Tomography — Undergo PET scan

Primary Outcomes

• Recommended Phase II Dose (RP2D) (Up to 28 days)

Secondary Outcomes

• 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)

Full Eligibility Criteria

Inclusion Criteria:

* 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
* 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 impa

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• UM Sylvester Comprehensive Cancer Center at Coral Gables, Coral Gables, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Deerfield Beach, Deerfield Beach, Florida, United States
• University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Plantation, Plantation, Florida, United States
• University of Kentucky/Markey Cancer Center, Lexington, Kentucky, United States
• Case Western Reserve University, Cleveland, Ohio, United States
• Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States
• University of Pittsburgh Cancer Institute (UPCI), Pittsburgh, Pennsylvania, United States
• Huntsman Cancer Institute/University of Utah, Salt Lake City, Utah, United States
• ...and 1 more locations

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer
• EGFR-mutated Lung Cancer
• Stage IV Lung Cancer
• Metastatic Lung Cancer
• Tyrosine Kinase Inhibitor Resistance
• Oncology
• Thoracic Oncology
• Targeted Cancer Therapy
• Lung Adenocarcinoma
• Cancer Genomics

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