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

BDTX-1535 was designed to block a growth signal important to some cancers. BDTX-1535 is being tested in this study to see if it can be given safely to people who have tumors that can be dependent on that growth because of changes in a protein called EGFR. These gene changes are called amplifications, mutations or alterations and are found only in the tumors. Your tests have shown that your tumor has an alteration in EGFR. These changes do not exist in normal tissue, so there is an opportunity to block the growth of the cancer cells while allowing signals used by normal cells. This study is being done to find answers to the following:

• How often and how much of the study drug should be given to cancer patients?
• What are the side effects of the study drug?
• How long after dosing does the study drug remain in your body with and without food?
• How does the study drug affect biomarkers? Biomarkers are substances in your body that can be measured to help track the status of your disease, such as DNA, RNA, and proteins. These substances in blood will be tested to learn if the study drug changes the way the cancer behaves.
• Can the study drug help patients with your type of cancer?
• For more information, please visit: https://clinicaltrials.gov/study/NCT05256290

Inova Schar Cancer Institute
A division of Inova Fairfax Hospital
8081 Innovation Park Drive 
Fairfax, VA 22031

• Adults 18 years of age or older or as permitted by applicable local regulations at the time of providing informed consent.
• Patients with GBM or NSCLC who meet the disease-specific criteria and have disease progression after treatment with available therapies that are known to confer clinical benefit, or who refuse or are intolerant to treatment (excluding the patients with treatment-naïve NSCLC, for which one previous cycle of chemotherapy or immune checkpoint inhibitor is permitted).
• Life expectancy of ≥ 3 months
• Adequate bone marrow or organ function as demonstrated by all the following laboratory values:
  a. Estimated (using the Cockcroft-Gault equation) or measured creatinine clearance ≥ 60 mL/min, or Serum Creatinine within normal limits per institution.
  b. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 × ULN. AST or ALT ≤ 5.0 × ULN in the presence of liver metastases.
  c. Total bilirubin < 1.5 × ULN (for patients with Gilbert's syndrome, bilirubin < 3.0 × ULN is allowed).
  d. Absolute neutrophil count (ANC) > 1000 cells/μL
  e. Hemoglobin > 8.5 g/dL. (Note: transfusion is allowed up to 1 week prior to enrollment)
  f. Platelet count
• For patients who are being treated with corticosteroids, the dose should be a maximum of 4 mg dexamethasone (or equivalent) per day and stable or decreasing during the 5 days prior to start of study drug.

• Known resistant mutations in tumor tissue or ctDNA, including EGFR T790M, EGFR exon 20 insertion mutations, MET (including MET amplification), KRAS, or HER2 (C805S, T798I, or T862A). Patients with suspected small cell transformation are not eligible.
• Dose escalation Only: GBM patient treated with a prior EGFR inhibitor. (Note: this specific exclusion does not apply to NSCLC since patients with NSCLC are required to have had appropriate approved EGFR inhibitors prior to enrollment excluding the first line non-classical driver cohort).
• Symptomatic leptomeningeal disease.
• Symptomatic brain metastases or spinal cord compression requiring increasing corticosteroids or urgent clinical intervention.
• Unresolved Grade 2 or greater toxicity from prior therapy (excluding alopecia, lymphopenia, or hypothyroidism or Grade 2 neuropathy adequately managed with stable medication) according to the NCI CTCAE Version 5.0.
• Significant cardiovascular disease
• Clinically significant abnormal electrocardiogram (ECG) findings
• Major surgery within 4 weeks before first dose of study drug or scheduled for surgery during projected course of the study.