Clinical trial NCT05256290: Phase 1/2 Study of BDTX-1535 in Patients With Glioblastoma or Non-Small Cell Lung Cancer With EGFR Mutations
Official title: A Phase 1/2 Study to Assess BDTX-1535, an Oral EGFR Inhibitor, in Patients With Glioblastoma or Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Keywords: EGFR alterations
EGFR L858R
EGFR Exon 19 del
EGFR inhibitor
intrinsic resistance NSCLC EGFR
acquired resistance NSCLC EGFR
intracranial disease
brain metastases
central nervous system metastases
CNS metastases
uncommon NSCLC EGFR mutations
C797S acquired resistance EGFR mutation
non-classical NSCLC EGFR mutations
classical NSCLC EGFR mutations
EGFR PACC NSCLC mutations
EGFR E709A/G/K/Q/V
EGFR E709_T710delinsD/T
EGFR G719A/C/D/R/S
EGFR G724S
EGFR L718Q/V
EGFR L747S/P, L747_A750delinsP, L747_P753delinsS
Second-site EGFR mutation
Lead sponsor: Black Diamond Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-25
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: The first treatment 21-day cycle (Cycle 1)
measure: Phase 2: To assess antitumor efficacy of BDTX-1535
timeFrame: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
Secondary outcomes:
measure: Phase 1 and Phase 2: Incidence and severity of treatment-emergent adverse events (TEAEs)
timeFrame: Through study completion, approximately 1 year
measure: Phase 1 and Phase 2: To characterize the plasma concentration of BDTX-1535 following single and multiple dosing
timeFrame: 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)
measure: 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)
timeFrame: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
measure: Phase 1: To assess the effect of tablet formulation on the plasma concentration of BDTX-1535
timeFrame: 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)
measure: Phase 1: To assess the effect of food on the plasma concentration of BDTX-1535
timeFrame: 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)
measure: Phase 2: To assess duration of tumor response by RECIST version 1.1
timeFrame: Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
measure: Phase 2: To assess progression free survival by RECIST version 1.1
timeFrame: Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
measure: Phase 2: To evaluate CNS ORR by RANO for brain metastases criteria (RANO-BM)
timeFrame: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
measure: Phase 2: To assess NSCLC disease-related symptoms and change of symptoms with BDTX-1535 treatment
timeFrame: 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)
measure: Phase 2: To assess treatment related side effects with BDTX-1535
timeFrame: 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)
measure: Phase 2: To determine the optimal dosage of BDTX-1535 (100 mg or 200 mg daily dose)
timeFrame: At least the first treatment 21-day cycle (Cycle 1) for select patients enrolled into the Phase 2
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center (Duarte Campus)
state: California
city: Huntington Beach
country: United States
facility: City of Hope Huntington Beach
state: California
city: Irvine
country: United States
facility: City of Hope Orange County Lennar Foundation Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials
state: California
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Washington
country: United States
facility: Sibley Memorial Hospital Johns Hopkins Medicine
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic- Jacksonville
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute - Baptist Health South Florida
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Emory Winship Cancer Center
state: Georgia
city: Honolulu
country: United States
facility: UHP- University of Hawaii Cancer Center
state: Hawaii
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Fairway
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Bethesda
country: United States
facility: The Center for Cancer and Blood Disorders
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic- Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Hospitals - Lineberger Comprehensive Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Durham VA Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State Comprehensive Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University/Sidney Kimmel Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Hillman Cancer Center
state: Pennsylvania
city: Germantown
country: United States
facility: The West Clinic PLLC, dba West Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Fairfax
country: United States
facility: Next Ocology
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center/University of Washington
state: Washington
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center- University Health Network
state: Ontario
Study officials:
affiliation: Black Diamond Therapeutics
name: Black Diamond Therapeutics
role: STUDY_DIRECTOR
References: