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

Protocol # :
Non-Small Cell Lung Cancer
Advanced Non-Small Cell Squamous Lung Cancer
Metastatic Lung Non-Small Cell Carcinoma
Metastatic Lung Cancer
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
Disease Sites
Brain and Nervous System
Principal Investigator
Wen, Patrick, Yung

Trial Description

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.

Eligibility Requirements

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

- 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,

- 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

- 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)

- Poorly controlled gastrointestinal disorders.