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

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 brainmetastases.

• Disease progression following or intolerance of standard of care (excluding patientsin the treatment-naïve non-classical driver cohort):

• Cohort 1 (Non-Classical driver cohort): Advanced/metastatic NSCLC with anon-classical driver EGFR mutation (eg, G719X) following up to 2 lines oftherapy with only 1 prior EGFR TKI regimen (third-generation preferred; otherapproved EGFR TKI acceptable).

• Cohort 2 (Acquired resistance C797S cohort): Advanced/metastatic NSCLC with theacquired 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-naïveadvanced/metastatic NSCLC with a non-classical driver EGFR mutation (1 cycle ofchemotherapy or immune checkpoint inhibitor are permitted). Patients withco-occurring L858R mutations and a non-classical mutation are eligible forinclusion.

• Identification of one (or more) of the following EGFR mutations by Next GenerationSequencing (NGS) as determined by a local assay performed in a validated laboratoryin 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 generationEGFR TKI (eg, osimertinib), the NGS report within 6 months prior to the startof Screening is acceptable. For patients in Cohort 2, the NGS report must befrom the last disease progression on the immediate prior therapy. For patientsin Cohort 3, the NGS report must be at the time of diagnosis.

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 treatmentof 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 clinicalintervention.

• 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 activetherapy within the next 2 years.

• Active hepatitis B or C infection and/or known human immunodeficiency virus (HIV)carrier.

• Poorly controlled gastrointestinal disorders.