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

NCT ID: NCT05256290

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-31
• Study Completion Date: 2026-06-30

Brief Summary

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

silevertinib (BDTX-1535) monotherapy

Intervention Type: DRUG

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.

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)

Group Type: EXPERIMENTAL

silevertinib (BDTX-1535) monotherapy

Intervention Type: DRUG

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.

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)

Group Type: EXPERIMENTAL

silevertinib (BDTX-1535) monotherapy

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Black Diamond Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Black Diamond Therapeutics

Role: STUDY_DIRECTOR

Black Diamond Therapeutics

Locations

University of Alabama

Birmingham, Alabama, United States

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

City of Hope Huntington Beach

Huntington Beach, California, United States

City of Hope Orange County Lennar Foundation Cancer Center

Irvine, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Sibley Memorial Hospital Johns Hopkins Medicine

Washington D.C., District of Columbia, United States

Mayo Clinic- Jacksonville

Jacksonville, Florida, United States

Miami Cancer Institute - Baptist Health South Florida

Miami, Florida, United States

UHP- University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

University of Kansas Cancer Center

Fairway, Kansas, United States

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic- Rochester

Rochester, Minnesota, United States

Siteman Cancer Center

St Louis, Missouri, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Columbia University Irving Medical Center

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

UNC Hospitals - Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Tennessee Oncology

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Inova Schar Cancer Institute

Fairfax, Virginia, United States

Next Ocology

Fairfax, Virginia, United States

Fred Hutchinson Cancer Center/University of Washington

Seattle, Washington, United States

Countries

United States

Other Identifiers

BDTX-1535-101

Identifier Type: -

Identifier Source: org_study_id