Black Diamond Therapeutics (BDTX) Study Update summary

Key findings from phase II study in non-small cell lung cancer

• Silevertinib showed a 60% overall response rate in frontline NSCLC patients with non-classical EGFR mutations, with responses across 35 unique mutations and a disease control rate over 90%.

• Robust CNS activity was observed, with an 86% CNS response rate and confirmed responses in 6 of 7 patients with target brain lesions.

• Median follow-up was 7.2 months; median PFS and duration of response are not yet reached, with early durability trends and 29 patients remaining on therapy, the longest over 19 months.

• Adverse events were consistent with the EGFR TKI class, including rash, stomatitis, diarrhea, and paronychia, managed with dose reductions and supportive care, with no new safety signals.

• Silevertinib demonstrated efficacy in both PACC and classical-like NCMs, including compound mutations, and maintained activity after dose reductions.

Clinical expert perspectives and unmet need

• Non-classical EGFR mutations represent about 25% of newly diagnosed NSCLC and have limited benefit from current EGFR TKIs, especially in patients with CNS metastases.

• CNS metastasis is common and challenging; effective brain-penetrant therapies are needed to avoid toxic local treatments.

• Silevertinib provided durable responses in patients with brain metastases and in those resistant to earlier EGFR TKIs.

• EGFR TKI-related toxicities are manageable with established protocols, and dose reductions do not compromise outcomes.

Planned phase II trial in glioblastoma (GBM)

• Silevertinib is designed to overcome past failures of EGFR inhibitors in GBM by targeting a broad spectrum of EGFR alterations, including variant 3, and achieving high CNS penetrance.

• Preclinical and early clinical data show potent activity against EGFR variant 3 and other alterations, with improved survival in intracranial tumor models.

• Over 60 recurrent GBM patients have been treated, with encouraging tolerability and preliminary efficacy; pharmacologically relevant brain tumor exposure was confirmed.

• The upcoming randomized phase II trial will enroll about 150 newly diagnosed unmethylated/MGMT-negative GBM patients with EGFR variant 3, randomizing to temozolomide alone or silevertinib plus temozolomide, with initial data expected in 2028.

• Primary endpoint is PFS by blinded review, with OS as secondary; the trial is powered for robust proof of concept and will be overseen by an Independent Data Monitoring Committee.