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