Black Diamond Therapeutics (BDTX) Study Update summary

Study background and objectives

• BDTX-1535 is a fourth-generation, oral, brain-penetrant EGFR TKI targeting over 50 oncogenic mutations, including classical, non-classical, and C797S resistance mutations in NSCLC.

• Designed to spare wild-type EGFR, BDTX-1535 aims for favorable tolerability and CNS penetration.

• Phase 2 cohorts are ongoing in both recurrent and frontline EGFRm NSCLC, focusing on non-classical driver mutations and C797S resistance.

EGFR mutation landscape and unmet need

• The EGFR mutation landscape in NSCLC has evolved, revealing a significant proportion of non-classical and TKI-resistant mutations.

• PACC-NCMs and C797S mutations together comprise about 20–23% of recurrent EGFRm NSCLC, representing a key unmet need.

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

Study design and patient population

• Phase II trial evaluated BDTX-1535 in relapsed/refractory NSCLC patients with non-classical EGFR mutations and C797S resistance mutations, including treatment-naive NCMs.

• Patients were divided into cohorts based on mutation type: non-classical, C797S resistance, and treatment-naive NCMs.

• Dose selection and safety assessment were based on 40 patients randomized to 100 mg or 200 mg daily, with 200 mg chosen for pivotal development.

• Efficacy analysis focused on 19 patients with on-target resistance mutations (PACC and/or C797S), with a median age of 62 and 22% having CNS metastases at baseline.

• Baseline characteristics included a high proportion with brain metastases and visceral disease, indicating poor prognosis.