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Testing of the Anti Cancer Drugs CB-839 HCl (Telaglenastat) and MLN0128 (Sapanisertib) in Advanced Stage Non-small Cell Lung Cancer

Study Purpose

This phase I/Ib trial studies the side effects and best dose of CB-839 HCl when given together with sapanisertib in treating patients with non-small cell lung cancer that has spread to other places in the body (advanced). CB-839 HCl and sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Patients must have stage IV or recurrent/metastatic NSCLC and have progressed on or after platinum-based chemotherapy and/or PD-(L)1 immune checkpoint inhibitor.
Patients with autoimmune or other conditions where PD-(L)1 checkpoint inhibitors are contraindicated are eligible with progression on or after platinum-based chemotherapy or immunotherapy.
  • - Dose escalation: patients with NSCLC known to harbor EGFR, ALK, ROS1, BRAF V600E/K activating mutations must have also progressed on appropriate Food and Drug Administration (FDA)-approved targeted therapies to be eligible for dose escalation.
  • - Dose expansion: patients must have stage IV or recurrent/metastatic NSCLC harboring 1) NFE2L2 mutations (LSCC); 2) KEAP1 mutations (LSCC); KRAS/KEAP1 or KRAS/NFE2L2 co-mutations (non-squamous NSCLC); or 3) LSCC WT for NFE2L2 or KEAP1 who have progressed on or after platinum-based chemotherapy and/or PD (L)1 immune checkpoint inhibitors or immunotherapy.
Acceptable molecular testing includes Foundation ACT circulating tumor deoxyribonucleic acid (ctDNA) or Guardant 360 ctDNA in plasma or Foundation One or Memorial Sloan Kettering Cancer Center (MSK)-Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) in tumor tissue. Patients with autoimmune or other conditions where PD-(L)1 checkpoint inhibitors are contraindicated are eligible with progression on or after platinum-based chemotherapy or immunotherapy.
  • - Eastern Cooperative Oncology Group (ECOG) - American College of Radiology Imaging Network (ACRIN) performance status 0-2.
  • - Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • - Fasting blood glucose (FBS) =< 130 and hemoglobin A1C (HGBA1C) =< 8.0% and fasting triglycerides =< 300 mg/dL.
  • - Tissue accessible for fine needle and/or core needle biopsy for molecular testing (for expansion cohorts only) - Absolute neutrophil count >= 1,500/mcL.
  • - Platelets >= 100,000/mcL.
  • - Total bilirubin =< 1.5 x upper limit of normal (ULN) - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (=< 5 x ULN if liver metastases are present) - Creatinine =< 1.3 mg/dL OR.
  • - Glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2.
  • - Hemoglobin >= 9 g/dL (without transfusion within 1 week preceding study drug administration) - For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • - Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured.
For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • - Because no dosing or adverse event data are currently available on the use of CB-839 HCl (telaglenastat) in combination with MLN0128 (sapanisertib) in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
  • - 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 stable, treated, asymptomatic 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 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.
  • - Females of childbearing potential must have a negative pregnancy test (=< 14 days) prior to start of trial treatment.
  • - Females who: - Are postmenopausal for at least 1 year before the screening visit, OR.
  • - Are surgically sterile, OR.
  • - If they are of childbearing potential, agree to practice 1 effective method of contraception and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer as mandated by local labeling [e.g. USPI, SmPC, etc]) after the last dose of study drug, OR.
  • - Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient (Periodic abstinence [e.g. calendar, ovulation, symptothermal postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.
Female and male condoms should not be used together)
  • - Agree not to donate egg(s) during the course of this study or within 90 days after receiving their last dose of study drug.
  • - Male patients, even if surgically sterilized (i.e. status post vasectomy), must agree to the following contraceptive requirements: - Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR.
  • - Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient (Periodic abstinence [e.g. calendar, ovulation, symptothermal postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.
Female and male condoms should not be used together)
  • - Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug.
  • - The effects of CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib) on the developing human fetus are unknown.
For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CB-839 HCl (telaglenastat) administration.
  • - 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.

Exclusion Criteria:

  • - Patients who have had chemotherapy within 3 weeks or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
  • - Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia.
  • - Patients who are receiving any other investigational agents.
  • - History of allergic reactions attributed to compounds of similar chemical or biologic composition to CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib) - CB-839 HCl (telaglenastat) is a weak in vitro inhibitor of CYP2C9.
Therefore, patients receiving any medications or substances that are substrates of CYP2C9 are eligible, but should use caution with substrates that have a narrow therapeutic index. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
  • - Patients with uncontrolled intercurrent illness.
  • - Patients with psychiatric illness/social situations that would limit compliance with study requirements.
  • - Pregnant women are excluded from this study because CB-839 HCl (telaglenastat) is an agent with the potential for teratogenic or abortifacient effects.
Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with CB-839 HCl (telaglenastat), breastfeeding should be discontinued if the mother is treated with CB-839 HCl (telaglenastat). These potential risks may also apply to MLN0128 (sapanisertib)
  • - Patients who are unable to swallow tablets.
  • - Human immunodeficiency virus (HIV)-infected patients.
  • - Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128 (sapanisertib).
In addition, patients with enteric stomata are also excluded.
  • - Significant active cardiovascular or pulmonary disease including: - Uncontrolled hypertension (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg).
Use of anti-hypertensive agents to control hypertension before cycle 1 day 1 is allowed.
  • - Pulmonary hypertension.
  • - Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas analysis or pulse oximetry on room air.
  • - Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement.
  • - Medically significant (symptomatic) bradycardia.
  • - History of arrhythmia requiring an implantable cardiac defibrillator.
  • - Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes) - Patients receiving systemic corticosteroids (either IV or oral steroids, excluding inhalers or low-dose hormone replacement therapy) within 1 week before administration of the first dose of study drugs.
  • - Patients who are taking proton pump inhibitors (PPIs) within 7 days of the first dose of study drug or who require treatment with PPIs throughout the trial or those who are taking H2 receptor antagonists within 24 hours of the first dose of study drug.
  • - Previous treatment with PI3K, AKT, dual PI3K/mTOR inhibitors, TORC1/2 inhibitors or TORC1 inhibitors.
  • - 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04250545
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

National Cancer Institute (NCI)
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Jonathan W Riess
Principal Investigator Affiliation City of Hope Comprehensive Cancer Center LAO
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

NIH
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Leptomeningeal Neoplasm, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Recurrent Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
Additional Details

PRIMARY OBJECTIVE:

  • I. To determine the safety and tolerability of glutaminase inhibitor CB-839 hydrochloride (CB-839 HCl) (telaglenastat) in combination with MLN0128 (sapanisertib) and determine the recommended phase 2 dose (RP2D) of the combination.
SECONDARY OBJECTIVES:
  • I. To observe and record anti-tumor activity.
  • II. To examine preliminary efficacy of CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib) in squamous cell lung cancers (LSCC) and in select, molecularly-defined non-small cell lung cancer (NSCLC) cohorts.
IIa. To evaluate the objective response rate (ORR), progression-free survival (PFS), and disease control rate (DCR) of patients treated with CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib). EXPLORATORY OBJECTIVES:
  • I. To correlate genomic and metabolomic signatures with response.
  • II. To evaluate metabolic response (18Glutamine [GLN]-positron emission tomography [PET]/computed tomography [CT]; 18Fluorodeoxyglucose [FDG]-PET/CT) in NSCLC tumors treated with CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib) in the dose expansion.
OUTLINE: This is a dose-escalation study of glutaminase inhibitor CB-839 hydrochloride. Patients receive glutaminase inhibitor CB-839 hydrochloride orally (PO) twice daily (BID) and sapanisertib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up quarterly.

Arms & Interventions

Arms

Experimental: Treatment (CB-839 HCl, sapanisertib)

Patients receive glutaminase inhibitor CB-839 hydrochloride PO BID and sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Interventions

Drug: - Sapanisertib

Given PO

Drug: - Telaglenastat Hydrochloride

Given PO

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

City of Hope Comprehensive Cancer Center, Duarte, California

Status

Recruiting

Address

City of Hope Comprehensive Cancer Center

Duarte, California, 91010

Site Contact

Site Public Contact

[email protected]

800-826-4673

City of Hope at Irvine Lennar, Irvine, California

Status

Recruiting

Address

City of Hope at Irvine Lennar

Irvine, California, 92618

Site Contact

Site Public Contact

877-467-3411

Keck Medicine of USC Koreatown, Los Angeles, California

Status

Recruiting

Address

Keck Medicine of USC Koreatown

Los Angeles, California, 90020

Site Contact

Site Public Contact

213-388-0908

Los Angeles General Medical Center, Los Angeles, California

Status

Recruiting

Address

Los Angeles General Medical Center

Los Angeles, California, 90033

Site Contact

Site Public Contact

[email protected]

323-865-0451

USC / Norris Comprehensive Cancer Center, Los Angeles, California

Status

Recruiting

Address

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033

Site Contact

Site Public Contact

323-865-0451

Sacramento, California

Status

Recruiting

Address

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817

Site Contact

Site Public Contact

916-734-3089

Memorial Sloan Kettering Cancer Center, New York, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Site Contact

Site Public Contact

212-639-7592