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Phase 1/2 Study of Silevertinib (BDTX-1535) in Patients With Glioblastoma or Non-Small Cell Lung Cancer With EGFR Mutations

Study Purpose

BDTX-1535-101 is an open-label, Phase 1 dose escalation and Phase 2 multiple cohort study designed to evaluate the safety, pharmacokinetics (PK), optimal dosage, central nervous system (CNS) activity, and antitumor activity of silevertinib (BDTX-1535). The study population comprises adults with either advanced/metastatic non-small cell lung cancer (NSCLC) with non-classical or acquired epidermal growth factor receptor (EGFR) resistance (EGFR C797S) mutations with or without CNS disease (in Phase 1 and Phase 2), or glioblastoma (GBM) expressing EGFR alterations (Phase 1 only). All patients will self-administer silevertinib (BDTX-1535) monotherapy by mouth in 21-day cycles. Phase 1 enrollment is now complete. Phase 2 is currently ongoing.

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

Phase 2 Eligibility: Key Inclusion Criteria Required for locally advanced or metastatic NSCLC:

  • - Measurable disease by RECIST 1.1 criteria.
  • - Adequate bone marrow or organ function.
  • - Life expectancy of ≥ 3 months.
  • - Sufficient performance status.
  • - Confirmed NSCLC, without small cell lung cancer transformation with or without brain metastases.
  • - Disease progression following or intolerance of standard of care (excluding patients in the treatment-naïve non-classical driver cohort): - Cohort 1 (Non-Classical driver cohort): Advanced/metastatic NSCLC with a non-classical driver EGFR mutation (eg, G719X) following up to 2 lines of therapy with only 1 prior EGFR TKI regimen (third-generation preferred; other approved EGFR TKI acceptable).
  • - Cohort 2 (Acquired resistance C797S cohort): Advanced/metastatic NSCLC with the acquired resistance C797S EGFR mutation following up to 2 lines of therapy, including only one EGFR TKI, which must be a third generation EGFR TKI (eg, osimertinib).
  • - Cohort 3 (First-line non-classical driver cohort): Treatment-naïve advanced/metastatic NSCLC with a non-classical driver EGFR mutation (1 cycle of chemotherapy or immune checkpoint inhibitor are permitted).
Patients with co-occurring L858R mutations and a non-classical mutation are eligible for inclusion.
  • - Identification of one (or more) of the following EGFR mutations by Next Generation Sequencing (NGS) as determined by a local assay performed in a validated laboratory in the absence of other known resistance mutations (eg, T790M, MET): - Non-classical driver EGFR mutations (eg, L861R, S768I, G719X).
  • - EGFR acquired resistance mutation (eg, C797S) to a 3rd generation EGFR TKI.
  • - For Phase 2, dose expansion, patients in Cohort 1 who received 3rd generation EGFR TKI (eg, osimertinib), the NGS report within 6 months prior to the start of Screening is acceptable.
For patients in Cohort 2, the NGS report must be from the last disease progression on the immediate prior therapy. For patients in Cohort 3, the NGS report must be at the time of diagnosis. Key

Exclusion Criteria:

  • - Known resistant mutations in tumor tissue or by liquid biopsy (eg, T790M, MET).
  • - Received more than 1 EGFR TKI therapy (ie, erlotinib or gefitinib) for the treatment of metastatic or recurrent EGFR NSCLC.
  • - Any history of interstitial lung disease related to EGFR TKI use.
  • - Symptomatic or radiographic leptomeningeal disease.
  • - Symptomatic brain metastases or spinal cord compression requiring urgent clinical intervention.
  • - Unresolved toxicity from prior therapy.
  • - Significant cardiovascular disease.
  • - Major surgery within 4 weeks of study entry or planned during study.
  • - Ongoing or recent anticancer therapy or radiation therapy.
  • - Evidence of malignancy (other than study-specific malignancies) requiring active therapy within the next 2 years.
  • - Active hepatitis B or C infection and/or known human immunodeficiency virus (HIV) carrier.
  • - Poorly controlled gastrointestinal disorders.

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.

 NCT05256290
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/Phase 2
Lead Sponsor

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

 Black Diamond Therapeutics, Inc.
Principal Investigator

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

 Black Diamond Therapeutics
Principal Investigator Affiliation Black Diamond Therapeutics
Agency Class

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

 Industry
Overall Status Active, not recruiting
Countries Canada, United States
Conditions

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

 Non-Small Cell Lung Cancer, Advanced Non-Small Cell Squamous Lung Cancer, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Lung Cancer, NSCLC, Advanced Lung Carcinoma, Epidermal Growth Factor Receptor C797S, Epidermal Growth Factor Receptor G719X, EGF-R Positive Non-Small Cell Lung Cancer, EGFR-TKI Resistant Mutation
Arms & Interventions

Arms

Experimental: Phase 1 Dose Escalation - Monotherapy (Recruitment Closed)

- Advanced/metastatic NSCLC with acquired resistance EGFR mutation (eg, C797S), following a 3rd generation EGFR inhibitor in the 1st line setting (in the absence of concurrent T790M). - Advanced/metastatic NSCLC with non-classical EGFR mutation (eg, G719X) following standard-of-care therapy with an EGFR inhibitor - Recurrent GBM with confirmed EGFR alterations (including amplification, mutation, and/or variant)

Experimental: Phase 2 Cohort 1: NSCLC EGFR Non-Classical Driver Mutations

Advanced/metastatic NSCLC with a non-classical driver EGFR mutation following up to 2 lines of therapy with only 1 prior EGFR targeted regimen (third-generation preferred; other approved EGFR inhibitors acceptable)

Experimental: Phase 2 Cohort 2: NSCLC EGFR Acquired Resistance (C797S) Mutation

Advanced/metastatic NSCLC with the acquired resistance C797S EGFR mutation following up to 2 lines of therapy, including only 1 EGFR targeted regimen, which must be a third generation EGFR TKI (eg, osimertinib)

Experimental: Phase 2 Cohort 3: Treatment Naive NSCLC EGFR Non-Classical Driver Mutations

Treatment-naïve (first-line) advanced/metastatic NSCLC with a non-classical driver EGFR mutation (1 cycle of chemotherapy or immune checkpoint inhibitor are permitted). Patients with co-occurring L858R mutations and a non-classical mutation are eligible for inclusion.

Interventions

Drug: - silevertinib (BDTX-1535) monotherapy

Silevertinib (BDTX-1535) is a 4th generation irreversible brain penetrant EGFR MasterKey inhibitor, which targets a family of oncogenic EGFR classical and non-classical driver and resistance mutations in NSCLC.

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.

University of Alabama, Birmingham, Alabama

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University of Alabama

Birmingham, Alabama, 35294

Banner MD Anderson Cancer Center, Gilbert, Arizona

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Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234

Duarte, California

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City of Hope Comprehensive Cancer Center (Duarte Campus)

Duarte, California, 91010

City of Hope Huntington Beach, Huntington Beach, California

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City of Hope Huntington Beach

Huntington Beach, California, 92648

Irvine, California

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City of Hope Orange County Lennar Foundation Cancer Center

Irvine, California, 92618

Cedars Sinai Medical Center, Los Angeles, California

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Cedars Sinai Medical Center

Los Angeles, California, 90048

Valkyrie Clinical Trials, Los Angeles, California

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Valkyrie Clinical Trials

Los Angeles, California, 90067

Rocky Mountain Cancer Center, Lone Tree, Colorado

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Rocky Mountain Cancer Center

Lone Tree, Colorado, 80124

Washington, District of Columbia

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Sibley Memorial Hospital Johns Hopkins Medicine

Washington, District of Columbia, 20016

Mayo Clinic- Jacksonville, Jacksonville, Florida

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Mayo Clinic- Jacksonville

Jacksonville, Florida, 32224

Miami, Florida

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Miami Cancer Institute - Baptist Health South Florida

Miami, Florida, 33176

Orlando Health Cancer Institute, Orlando, Florida

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Orlando Health Cancer Institute

Orlando, Florida, 32806

Emory Winship Cancer Center, Atlanta, Georgia

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Emory Winship Cancer Center

Atlanta, Georgia, 30322

UHP- University of Hawaii Cancer Center, Honolulu, Hawaii

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UHP- University of Hawaii Cancer Center

Honolulu, Hawaii, 96813

Chicago, Illinois

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Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611

Indiana University, Indianapolis, Indiana

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Indiana University

Indianapolis, Indiana, 46202

University of Kansas Cancer Center, Fairway, Kansas

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University of Kansas Cancer Center

Fairway, Kansas, 66205

Johns Hopkins Bayview Medical Center, Baltimore, Maryland

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Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224

Bethesda, Maryland

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The Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817

Dana-Farber Cancer Institute, Boston, Massachusetts

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Address

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115

Mayo Clinic- Rochester, Rochester, Minnesota

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Address

Mayo Clinic- Rochester

Rochester, Minnesota, 55905

Siteman Cancer Center, Saint Louis, Missouri

Status

Address

Siteman Cancer Center

Saint Louis, Missouri, 63110

Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire

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Address

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756

Montefiore Medical Center, Bronx, New York

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Address

Montefiore Medical Center

Bronx, New York, 10461

Memorial Sloan Kettering Cancer Center, New York, New York

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Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10021

New York, New York

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Columbia University Irving Medical Center

New York, New York, 10032

Chapel Hill, North Carolina

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UNC Hospitals - Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27514

Durham VA Medical Center, Durham, North Carolina

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Durham VA Medical Center

Durham, North Carolina, 27705

Cleveland Clinic, Cleveland, Ohio

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Cleveland Clinic

Cleveland, Ohio, 44195

Ohio State Comprehensive Cancer Center, Columbus, Ohio

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Address

Ohio State Comprehensive Cancer Center

Columbus, Ohio, 43210

Philadelphia, Pennsylvania

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Thomas Jefferson University/Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107

Pittsburgh, Pennsylvania

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University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

Germantown, Tennessee

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Address

The West Clinic PLLC, dba West Cancer Center

Germantown, Tennessee, 38138

Tennessee Oncology, Nashville, Tennessee

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Address

Tennessee Oncology

Nashville, Tennessee, 37203

Mary Crowley Cancer Research, Dallas, Texas

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Mary Crowley Cancer Research

Dallas, Texas, 75230

Dallas, Texas

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Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246

Houston, Texas

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The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Inova Schar Cancer Institute, Fairfax, Virginia

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Address

Inova Schar Cancer Institute

Fairfax, Virginia, 22031

Next Ocology, Fairfax, Virginia

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Address

Next Ocology

Fairfax, Virginia, 22031

Seattle, Washington

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Address

Fred Hutchinson Cancer Center/University of Washington

Seattle, Washington, 98109

International Sites

Toronto, Ontario, Canada

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Address

Princess Margaret Cancer Center- University Health Network

Toronto, Ontario, M5G 2M9

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