Phase 1/2 Study of Silevertinib (BDTX-1535) in Patients With Glioblastoma or Non-Small Cell Lung Cancer With EGFR Mutations

Prior treatment

• Unresolved toxicity from prior therapy.
• Major surgery within 4 weeks of study entry or planned during study.
• Ongoing or recent anticancer therapy or radiation therapy.

Other illness

• Symptomatic or radiographic leptomeningeal disease.
• Significant cardiovascular disease.
• 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.

Lab values

• 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.

Other

• Known resistant mutations in tumor tissue or by liquid biopsy (eg, T790M, MET).
• Symptomatic brain metastases or spinal cord compression requiring urgent clinical intervention.

• 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). Patients with co-occurring L858R mutations and a non-classical mutation are eligible for inclusion.
• 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.
  • For Phase 2, dose expansion, patients in Cohort 1 who received 3rd generation EGFR TKI (eg, osimertinib), the NGS report within 6 months prior to the start of Screening is acceptable. For patients in Cohort 2, the NGS report must be from the last disease progression on the immediate prior therapy. For patients in Cohort 3, the NGS report must be at the time of diagnosis.

Criteria the registry did not label

• Phase 2 Eligibility: