Phase 1/2 Study of BDTX-1535 in Patients With Glioblastoma or Non-Small Cell Lung Cancer With EGFR Mutations
- Conditions
- Non-Small Cell Lung CancerMetastatic Lung Non-Small Cell CarcinomaEGFR-TKI Resistant MutationAdvanced Non-Small Cell Squamous Lung CancerMetastatic Lung CancerNSCLCAdvanced Lung CarcinomaEpidermal Growth Factor Receptor C797SEpidermal Growth Factor Receptor G719XEGF-R Positive Non-Small Cell Lung Cancer
- Interventions
- Drug: BDTX-1535 monotherapy
- Registration Number
- NCT05256290
- Lead Sponsor
- Black Diamond Therapeutics, Inc.
- 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 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 BDTX-1535 monotherapy by mouth in 21-day cycles.
Phase 1 enrollment is now complete. Phase 2 is currently enrolling.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
Not provided
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2 Cohort 1: NSCLC EGFR Non-Classical Driver Mutations BDTX-1535 monotherapy 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) Phase 2 Cohort 2: NSCLC EGFR Acquired Resistance (C797S) Mutation BDTX-1535 monotherapy 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) Phase 2 Cohort 3: Treatment Naive NSCLC EGFR Non-Classical Driver Mutations BDTX-1535 monotherapy 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. Phase 1 Dose Escalation - Monotherapy (Recruitment Closed) BDTX-1535 monotherapy * 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)
- Primary Outcome Measures
Name Time Method Phase 1 Dose Escalation: To determine the maximum tolerated dose (MTD), if one exists, and the preliminary recommended Phase 2 dose(s) (RP2D[s]) of BDTX-1535 The first treatment 21-day cycle (Cycle 1) Dose-limiting toxicities (DLTs) in Cycle 1
Phase 2: To assess antitumor efficacy of BDTX-1535 Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) Objective response rate (ORR) as assessed by Investigator using RECIST version 1.1
- Secondary Outcome Measures
Name Time Method Phase 1 and Phase 2: Incidence and severity of treatment-emergent adverse events (TEAEs) Through study completion, approximately 1 year Phase 1 and Phase 2: To characterize the plasma concentration of BDTX-1535 following single and multiple dosing Cycle 1 Days 1, 2, 15, and 16, Cycles 2 to 5 Day 1, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 21 days) Phase 1: To assess the preliminary antitumor activity of BDTX-1535 by objective response as assessed by RECIST version 1.1 (for patients with NSCLC) or Response Assessment in Neuro-oncology (RANO) (for patients with GBM) Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) Phase 1: To assess the effect of tablet formulation on the plasma concentration of BDTX-1535 Two timepoints during the first cycle: Cycle 0 (7 days prior to Cycle 1 Day 1) and Cycle 1 Day 1 only (each cycle is 21 days) Phase 1: To assess the effect of food on the plasma concentration of BDTX-1535 Two timepoints during the first cycle: Cycle 0 (7 days prior to Cycle 1 Day 1) and Cycle 1 Day 1 only (each cycle is 21 days) Phase 2: To assess duration of tumor response by RECIST version 1.1 Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) Phase 2: To assess progression free survival by RECIST version 1.1 Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) Phase 2: To evaluate CNS ORR by RANO for brain metastases criteria (RANO-BM) Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) Phase 2: To assess NSCLC disease-related symptoms and change of symptoms with BDTX-1535 treatment At select timepoints: Cycle 1 Day, Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1, and at study completion, approximately 1 year (each cycle is 21 days) Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ); Verbal rating scale used (for example: Never/Rarely/Sometimes/Often/Always)
Phase 2: To assess treatment related side effects with BDTX-1535 At select timepoints: Cycle 1 Day, Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1, and at study completion, approximately 1 year (each cycle is 21 days) National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (NCI-PRO-CTCAE) Survey: Rating scale used (for example never/rarely/occasionally/frequently/almost constantly)
Phase 2: To determine the optimal dosage of BDTX-1535 (100 mg or 200 mg daily dose) At least the first treatment 21-day cycle (Cycle 1) for select patients enrolled into the Phase 2
Trial Locations
- Locations (42)
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, 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
University of Alabama
🇺🇸Birmingham, Alabama, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
City of Hope Comprehensive Cancer Center (Duarte Campus)
🇺🇸Duarte, California, 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
City of Hope- Long Beach
🇺🇸Long Beach, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
Rocky Mountain Cancer Center
🇺🇸Lone Tree, Colorado, United States
Sibley Memorial Hospital Johns Hopkins Medicine
🇺🇸Washington, District of Columbia, United States
Miami Cancer Institute - Baptist Health South Florida
🇺🇸Miami, Florida, United States
Emory Winship Cancer Center
🇺🇸Atlanta, Georgia, United States
Mayo Clinic- Jacksonville
🇺🇸Jacksonville, Florida, United States
Orlando Health Cancer Institute
🇺🇸Orlando, 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
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of Kansas Cancer Center
🇺🇸Fairway, Kansas, United States
Johns Hopkins Bayview Medical Center
🇺🇸Baltimore, Maryland, United States
The Center for Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Mayo Clinic- Rochester
🇺🇸Rochester, Minnesota, United States
Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
UNC Hospitals - Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Durham VA Medical Center
🇺🇸Durham, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Ohio State Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Thomas Jefferson University/Sidney Kimmel Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center - Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Prisma Health
🇺🇸Greenville, South Carolina, United States
The West Clinic PLLC, dba West Cancer Center
🇺🇸Germantown, Tennessee, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States