A Phase 1/2 Study to Assess BDTX-1535, an Oral EGFR Inhibitor, in Patients With Glioblastoma or Non-Small Cell Lung Cancer

Who is this study for? Patients with glioblastoma or non-small cell lung cancer
What treatments are being studied? BDTX-1535
Status: Active_not_recruiting
Location: See all (41) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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.

Locations
United States
Alabama
University of Alabama
Birmingham
Arizona
Banner MD Anderson Cancer Center
Gilbert
California
City of Hope Comprehensive Cancer Center (Duarte Campus)
Duarte
City of Hope Huntington Beach
Huntington Beach
City of Hope Orange County Lennar Foundation Cancer Center
Irvine
Cedars Sinai Medical Center
Los Angeles
Valkyrie Clinical Trials
Los Angeles
Colorado
Rocky Mountain Cancer Center
Lone Tree
Washington, D.c.
Sibley Memorial Hospital Johns Hopkins Medicine
Washington D.c.
Florida
Mayo Clinic- Jacksonville
Jacksonville
Miami Cancer Institute - Baptist Health South Florida
Miami
Orlando Health Cancer Institute
Orlando
Georgia
Emory Winship Cancer Center
Atlanta
Hawaii
UHP- University of Hawaii Cancer Center
Honolulu
Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago
Indiana
Indiana University
Indianapolis
Kansas
University of Kansas Cancer Center
Fairway
Massachusetts
Dana-Farber Cancer Institute
Boston
Maryland
Johns Hopkins Bayview Medical Center
Baltimore
The Center for Cancer and Blood Disorders
Bethesda
Minnesota
Mayo Clinic- Rochester
Rochester
Missouri
Siteman Cancer Center
St Louis
North Carolina
UNC Hospitals - Lineberger Comprehensive Cancer Center
Chapel Hill
Durham VA Medical Center
Durham
New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon
New York
Columbia University Irving Medical Center
New York
Memorial Sloan Kettering Cancer Center
New York
Montefiore Medical Center
The Bronx
Ohio
Cleveland Clinic
Cleveland
Ohio State Comprehensive Cancer Center
Columbus
Pennsylvania
Thomas Jefferson University/Sidney Kimmel Cancer Center
Philadelphia
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburgh
Tennessee
The West Clinic PLLC, dba West Cancer Center
Germantown
Tennessee Oncology
Nashville
Texas
Mary Crowley Cancer Research
Dallas
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas
The University of Texas MD Anderson Cancer Center
Houston
Virginia
Inova Schar Cancer Institute
Fairfax
Next Ocology
Fairfax
Washington
Fred Hutchinson Cancer Center/University of Washington
Seattle
Other Locations
Canada
Princess Margaret Cancer Center- University Health Network
Toronto
Time Frame
Start Date: 2022-03-31
Completion Date: 2026-06
Participants
Target number of participants: 200
Treatments
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.
Sponsors
Leads: Black Diamond Therapeutics, Inc.

This content was sourced from clinicaltrials.gov

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