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

NCT04250545 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 4 other identifiers: NCI-2020-00478PHI-11310327UM1CA186717
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 7

Brief 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). CB-839 HCl and sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 28 days

• 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.

  Up to 27 months

• 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.

  Up to 27 months

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to 27 months

• Progression Free Survival (PFS)

  Up to 27 months

• Disease Control Rate (DCR)

  Up to 27 months

Other Outcomes (2)

• Metabolic Response (18Glutamine [GLN]-Positron Emission Tomography [PET]/Computed Tomography [CT]; 18Fluorodeoxyglucose [FDG]-PET/CT)

  Up to 27 months

• Genomic and Metabolic Signatures

  Up to 27 months

Study Arms (1)

Treatment (CB-839 HCl, sapanisertib)

EXPERIMENTAL

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.

Drug: Sapanisertib; Drug: Telaglenastat Hydrochloride

Interventions

Sapanisertib DRUG

Given PO

Also known as: INK-128, INK128, MLN-0128, MLN0128, TAK-228

Treatment (CB-839 HCl, sapanisertib)

Telaglenastat Hydrochloride DRUG

Given PO

Also known as: CB-839 HCl, Glutaminase Inhibitor CB-839 Hydrochloride

Treatment (CB-839 HCl, sapanisertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

Location

Keck Medicine of USC Koreatown

Los Angeles, California, 90020, United States

Location

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Meningeal Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Lung Neoplasms

Interventions

sapanisertib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Brain Diseases; Central Nervous System Diseases

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

6262185265

Study Officials

• Jonathan W Riess

  City of Hope Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2020
• First Posted: January 31, 2020
• Study Start: October 26, 2020
• Primary Completion: November 21, 2025
• Study Completion (Estimated): November 21, 2026
• Last Updated: May 1, 2026
• Results First Posted: April 30, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (7)