Black Diamond Therapeutics (BDTX) Study Update summary

Study background and design

• BDTX-1535 is a fourth-generation, oral, brain-penetrant EGFR inhibitor targeting classical, non-classical (NCMs), and C797S resistance mutations in recurrent EGFR-mutant NSCLC, designed to spare wild-type EGFR and address CNS tumors.

• Phase II trial included patients who progressed after osimertinib, with three cohorts: non-classical mutations post-osimertinib, C797S resistance post-osimertinib, and treatment-naïve non-classical mutations; Cohort 3 is ongoing.

• Dose selection compared 100 mg vs. 200 mg; 200 mg was chosen for pivotal development due to favorable tolerability, pharmacokinetics, and efficacy.

EGFR mutation landscape and unmet need

• EGFR mutations in NSCLC are diverse, with non-classical and C797S resistance mutations representing a significant subset post-osimertinib and a key unmet need.

• PACC-NCMs and C797S mutations together comprise about 20% of recurrent EGFRm NSCLC.

• BDTX-1535 is positioned to address these mutations, which often retain EGFR onco-addiction.

Study design and patient population

• Preliminary data focus on 40 patients randomized to 100 mg or 200 mg in recurrent settings, with efficacy evaluable population at 200 mg including 27 patients (median age 62, 22% with CNS metastases).

• Phase 2 trial enrolled relapsed/refractory NSCLC patients with non-classical EGFR mutations and C797S resistance mutations.