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

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring EGFR alterations, L858R, G719X, EGFR inhibitor, newly diagnosed glioblastoma, newly diagnosed GBM, intrinsic resistance EGFR, acquired resistance EGFR, temozolomide, TMZ, intracranial disease, brain metastases, central nervous system metastases, CNS metastases, dose escalation, dose expansion, recommended phase 2 dose, RP2D, uncommon EGFR mutations, C797S EGFR mutations, recommended phase 2 combination dose, RP2cD Read More

Common Inclusion Criteria Required for ALL Patients

All patients must meet the common inclusion criteria required for all patients AND the respective criteria required for their specific disease for GBM and NSCLC (as applicable):

• Adults 18 years of age or older (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.

• Adequate bone marrow or organ function as demonstrated by all the following laboratory values:

  1. Estimated (using the Cockcroft-Gault equation) or measured creatinine clearance ≥ 60 mL/min.
  2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3 × ULN. AST or ALT ≤5.0 × ULN in the presence of liver metastases.
  3. Total bilirubin <1.5 × ULN (for patients with Gilbert's syndrome, bilirubin <3.0 × ULN is allowed).
  4. Absolute neutrophil count (ANC) >1000 cells/μL
  5. Hemoglobin >8.5 g/dL. (Note: transfusion is allowed up to 1 week prior to enrollment)
  6. Platelet count >100,000/μL. (Note: transfusion is allowed up to 1 week prior to enrollment)

Inclusion Criteria Required for GBM Patients Only

• In addition to the common inclusion criteria above, patients with GBM must also meet the following inclusion criteria:
• Histologically confirmed diagnosis of GBM according to 2021 WHO criteria IDHwt (wild-type IDH) GBM and astrocytoma with molecular features of GBM).
• A radiological diagnosis of recurrent disease following available standard of care therapy of surgery, radiation, and/or TMZ. Disease may be evaluable or measurable for dose escalation cohorts but must be measurable by RANO criteria for enrollment on the disease specific expansion.
• Tumor evidence of EGFR alterations including amplification, variants, or mutations as determined in a local laboratory by NGS, RNAseq, FISH, IHC, or Array GCH

Inclusion Criteria Required for NSCLC Patients Only:

• Patients with NSCLC must meet all of the following inclusion criteria, in addition to the common inclusion criteria applicable for all patients:
• Histologically or cytologically confirmed NSCLC, without small cell lung cancer transformation.
• Locally advanced or metastatic disease, with or without CNS metastases. Disease may be evaluable or measurable for dose escalation cohorts but must be measurable by RECIST v1.1 criteria for enrollment on the disease specific expansion cohorts.

• Disease progression following or intolerance of standard of care:

  1. NSCLC with uncommon EGFR mutations (eg, G719X), following standard of care therapy with an EGFR inhibitor.
  2. 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).
• EGFR mutations identified by NGS in the absence of other known resistance mutations (eg, T790M, MET)

Common Exclusion Criteria Required for ALL Patients:

• 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)
• GBM patient treated with a prior EGFR inhibitor
• Symptomatic Leptomeningeal disease. Asymptomatic untreated CNS and leptomeningeal disease is allowed and, when measurable, should be captured as target lesions
• Symptomatic brain metastases or spinal cord compression requiring increasing corticosteroids or urgent clinical intervention
• Unresolved Grade 2 or greater toxicity from prior therapy
• Significant cardiovascular disease
• Clinically significant abnormal electrocardiogram (ECG) findings