Clinical Trial Finder

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 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. 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 treatment of 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 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 or 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.

Arms

Experimental: Phase 1 Dose Escalation - Monotherapy (Recruitment Closed)

Advanced/metastatic 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). Advanced/metastatic NSCLC with non-classical EGFR mutation (eg, G719X) following standard-of-care therapy with an EGFR inhibitor Recurrent GBM with confirmed EGFR alterations (including amplification, mutation, and/or variant)

Experimental: Phase 2 Cohort 1: NSCLC EGFR Non-Classical Driver Mutations

Advanced/metastatic NSCLC with a non-classical driver EGFR mutation following up to 2 lines of therapy with only 1 prior EGFR targeted regimen (third-generation preferred; other approved EGFR inhibitors acceptable)

Experimental: Phase 2 Cohort 2: NSCLC EGFR Acquired Resistance (C797S) Mutation

Advanced/metastatic NSCLC with the acquired resistance C797S EGFR mutation following up to 2 lines of therapy, including only 1 EGFR targeted regimen, which must be a third generation EGFR TKI (eg, osimertinib)

Experimental: Phase 2 Cohort 3: Treatment Naive NSCLC EGFR Non-Classical Driver Mutations

Treatment-naïve (first-line) 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.

Interventions

Drug: - BDTX-1535 monotherapy

BDTX-1535 is a 4th generation irreversible brain penetrant EGFR MasterKey inhibitor, which targets a family of oncogenic EGFR classical and non-classical driver and resistance mutations in NSCLC.