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

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ClinicalTrials.gov Identifier: NCT05256290
Recruitment Status : Recruiting
First Posted : February 25, 2022
Last Update Posted : March 6, 2024
Sponsor:
Information provided by (Responsible Party):
Black Diamond Therapeutics, Inc.

Study Description
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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 multiforme (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.


Condition or disease Intervention/treatment Phase
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 Drug: BDTX-1535 monotherapy Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 31, 2022
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
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)
 Drug: BDTX-1535 monotherapy
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.
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)
 Drug: BDTX-1535 monotherapy
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.
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)
 Drug: BDTX-1535 monotherapy
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.
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)
 Drug: BDTX-1535 monotherapy
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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 [ Time Frame: The first treatment 21-day cycle (Cycle 1) ]
    Dose-limiting toxicities (DLTs) in Cycle 1

  2. Phase 2: To assess antitumor efficacy of BDTX-1535 [ Time Frame: 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 :
  1. Phase 1 and Phase 2: Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Through study completion, approximately 1 year ]
  2. Phase 1 and Phase 2: To characterize the plasma concentration of BDTX-1535 following single and multiple dosing [ Time Frame: 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) ]
  3. 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) [ Time Frame: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) ]
  4. Phase 1: To assess the effect of tablet formulation on the plasma concentration of BDTX-1535 [ Time Frame: 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) ]
  5. Phase 1: To assess the effect of food on the plasma concentration of BDTX-1535 [ Time Frame: 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) ]
  6. Phase 2: To assess duration of tumor response by RECIST version 1.1 [ Time Frame: Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) ]
  7. Phase 2: To assess progression free survival by RECIST version 1.1 [ Time Frame: Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) ]
  8. Phase 2: To evaluate CNS ORR by RANO for brain metastases criteria (RANO-BM) [ Time Frame: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) ]
  9. Phase 2: To assess NSCLC disease-related symptoms and change of symptoms with BDTX-1535 treatment [ Time Frame: 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)

  10. Phase 2: To assess treatment related side effects with BDTX-1535 [ Time Frame: 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)

  11. Phase 2: To determine the optimal dosage of BDTX-1535 (100 mg or 200 mg daily dose) [ Time Frame: At least the first treatment 21-day cycle (Cycle 1) for select patients enrolled into the Phase 2 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

  • 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.
    • NGS test must be obtained after progression on the most recent therapy; at the time of diagnosis for the patients in Cohort 3 only.

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05256290


Contacts
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Contact: BDTX Clinical Trial Navigation Service (866) 955-4397 blackdiamondtx@careboxhealth.com

Locations
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Sponsors and Collaborators
Black Diamond Therapeutics, Inc.
Investigators
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Study Director: Black Diamond Therapeutics Black Diamond Therapeutics
More Information
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Responsible Party: Black Diamond Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05256290    
Other Study ID Numbers: BDTX-1535-101
First Posted: February 25, 2022    Key Record Dates
Last Update Posted: March 6, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Black Diamond Therapeutics, Inc.:
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
PACC NSCLC mutations
E709A/G/K/Q/V
E709_T710delinsD/T
G719A/C/D/R/S
G724S
L718Q/V
L747S/P, L747_A750delinsP, L747_P753delinsS
Second-site EGFR mutation
Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Glioblastoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
 Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue