Clinical Trials

Trial Description:
BDTX-1535-101 is a first-in-human, open-label, Phase 1 dose escalation and multiple expansion cohort study designed to evaluate the safety, tolerability, pharmacokinetics (PK), central nervous system (CNS) activity, and preliminary antitumor activity of BDTX-1535. The study population comprises adults with either advanced/metastatic non-small cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor (EGFR) mutations with or without CNS disease, or glioblastoma multiforme (GBM) expressing EGFR alterations. All patients will self administer BDTX-1535 monotherapy in 21-day cycles. One expansion cohort will include patients with newly diagnosed GBM who will self administer BDTX-1535 in combination with temozolomide in 28-day cycles.

Eligibility Requirements:
Key Inclusion Criteria Required for ALL Patients:
- Evaluable or measurable disease in dose escalation and measurable disease only for dose expansion cohorts.
- Fulfills appropriate disease criteria as defined in Arms and Interventions
- Adequate bone marrow or organ function.
- Life expectancy of ≥ 3 months.
- Sufficient performance status.
Inclusion Criteria Required for NSCLC Patients Only:
- Confirmed NSCLC, without small cell lung cancer transformation.
- Locally advanced or metastatic disease, with or without central nervous system metastases.
- Disease progression following or intolerance of standard of care:
- Dose escalation cohorts only:
- NSCLC with uncommon EGFR mutation (eg, G719X) following standard-of-care therapy with an EGFR inhibitor.
- 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).
- Dose expansion cohorts only:
- NSCLC with intrinsic resistance EGFR mutation (eg, L858R, G719X) with up to 2 lines of standard-of-care therapy with an EGFR inhibitor.
- NSCLC with acquired resistance EGFR mutation (eg, C797S) with up to 2 lines of therapy, the first line of which must be a 3rd generation EGFR inhibitor (in the absence of concurrent T790M).
Note: therapies targeted for 3rd generation EGFR tyrosine kinase resistance are excluded for this patient population.
• Identification of one (or more) EGFR mutations identified in the absence of other known resistance mutations:
- Intrinsic resistance EGFR mutations [eg, L858R [dose expansion only], G719X).
- EGFR acquired resistance mutation (eg, C797S) to a 3rd generation EGFR inhibitor.
Inclusion Criteria Required for All GBM Patients Only:
- Confirmed diagnosis of GBM.
- Tumor evidence of EGFR alterations including variants, or mutations with or without amplifications (eg, A289T/V, G598V, S645C).
- Inclusion Criteria Required for Recurrent GBM Patients Only:
- Disease progression after treatment with available therapies or who refuse or are intolerant to treatment.
- Radiological diagnosis of recurrent disease following available standard-of-care therapy of surgery, radiation, and/or temozolomide.
Inclusion Criteria Required for Newly Diagnosed GBM Patients Only:
- Recovered from maximal debulking surgery (gross total resection or partial resection are also acceptable).
- Received radiation therapy and temozolomide at least 6 weeks, but no more than 8 weeks, prior to Cycle 1 Day 1.
Key Exclusion Criteria for ALL Patients:
- Known resistant mutations.
- For GBM patients only: treated with a prior EGFR inhibitor.
- 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.
- Ongoing or recent 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.

Protocol #: 22-295