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Leptomeningeal NeoplasmPhase 1NCT04250545

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

A Phase 1 study testing Sapanisertib and Telaglenastat Hydrochloride in people with Leptomeningeal Neoplasm and Metastatic Lung Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 7 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sapanisertib and Telaglenastat Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
7 sitesUnited States
Study dates
26 Oct 2020to 21 Nov 2026
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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 locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

  • Keck Medicine of USC Koreatown

    Los Angeles, California, 90020

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: A Phase 1 Trial of MLN0128 (Sapanisertib) and CB-839 HCl (Telaglenastat) in Advanced NSCLC Patients

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Sapanisertib, Telaglenastat Hydrochloride
Medical subject headings
Meningeal Neoplasms, Carcinoma, Non-Small-Cell Lung, Brain Neoplasms, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SapanisertibDrug

    Also called INK-128, INK128, MLN-0128, MLN0128

    Given PO

  • Telaglenastat HydrochlorideDrug

    Also called CB-839 HCl, Glutaminase Inhibitor CB-839 Hydrochloride

    Given PO

Study groups in NCT04250545
Study groupRoleWhat they receive
Treatment (CB-839 HCl, sapanisertib)ExperimentalPatients 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.
Receives: Drug: Sapanisertib; Drug: Telaglenastat Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose/Recommended Phase II Dose of MLN0128 (Sapanisertib) and CB-839 HCl (Telaglenastat) in Combination (Dose-escalation)

    Will be evaluated according to dose-limiting toxicities during cycle 1 graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 28 days

  2. Number of Subjects With Overall Response

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions or Disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Up to 27 months

  3. Median Progression Free Survival (PFS) (Dose-expansion)

    Median PFS will be determined using the Kaplan-Meier method. PFS is defined as the duration of time from the start of treatment to the time of progression or death, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions, or appearance of one or more new non-target lesions and/or unequivocal progression of existing non-target lesions.

    Measured: Up to 27 months

Secondary outcomes (3)

  1. Objective Response Rate (ORR)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions or Disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Up to 27 months

  2. Progression Free Survival (PFS)

    Will be evaluated by Kaplan-Meier estimates. PFS is defined as the duration of time from the start of treatment to the time of progression or death, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions, or appearance of one or more new non-target lesions and/or unequivocal progression of existing non-target lesions.

    Measured: Up to 27 months

  3. Disease Control Rate (DCR)

    DCR will be assessed by RECIST 1.1 criteria. DCR is defined as the proportion of patients who achieved either a complete response, partial response, or stable disease at any point during the treatment period. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions or Disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study; DCR = CR + PR + SD.

    Measured: Up to 27 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2020
  2. Study start26 Oct 2020
  3. Primary completion21 Nov 2025
  4. Study completion21 Nov 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04250545
Sponsor's protocol ID
NCI-2020-00478
Other IDs
NCI-2020-00478, PHI-113, 10327, 10327, UM1CA186717
Status last verified
May 2026
First submitted
30 Jan 2020
Last updated
26 May 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sapanisertib and Telaglenastat Hydrochloride in people with Leptomeningeal Neoplasm and Metastatic Lung Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose/Recommended Phase II Dose of MLN0128 (Sapanisertib) and CB-839 HCl (Telaglenastat) in Combination (Dose-escalation) (time frame: Up to 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04250545.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2026.

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