Black Diamond reports 86% CNS response rate for silevertinib in NSCLC

Black Diamond Therapeutics has disclosed detailed Phase 2 results for silevertinib in frontline non-small cell lung cancer patients harbouring non-classical EGFR mutations, presenting the data at the American Society of Clinical Oncology Annual Meeting on 30 May 2026. The Cambridge, Massachusetts company said the findings position silevertinib as a candidate best-in-class agent in a population with historically limited treatment options and a high rate of central nervous system involvement.

In 43 frontline patients dosed at 200 mg once daily, silevertinib produced an objective response rate of 60% by RECIST 1.1 criteria, a CNS objective response rate of 86% by RANO-BM criteria, and a disease control rate of 91%. Crucially, no patients developed de novo brain metastases during the study period. Preliminary median progression-free survival stood at 15.2 months (95% CI: 10.8, not estimable), and median duration of response had not yet been reached at the April 2026 data cut. More than half of the cohort, 53%, remained on therapy, with the longest on-treatment duration reaching 23.5 months.

Clinical profile and dose selection

The mutation coverage is notably broad: the trial enrolled patients across 25 unique non-classical EGFR variants, including compound mutations and PACC (P-Loop and C-Helix Compressing) mutations, and variant allele frequency reductions were observed in all evaluable patients. The Grade 3 or higher treatment-related adverse event rate was 28% following dose reduction, and the company reported that patients maintained or deepened responses after adjusting their dose. On the basis of integrated safety, pharmacokinetic and pharmacodynamic data, Black Diamond has selected 150 mg once daily as the dose for pivotal development.

Mark Velleca, president and chief executive, said the lack of de novo brain metastases was particularly encouraging, noting that approximately 80% of patients with non-classical EGFR mutations progress in the brain and around 40% present with brain metastases at diagnosis. The company is seeking FDA feedback on a pivotal development path in frontline non-classical EGFRm NSCLC and expects to provide an update in the fourth quarter of 2026.

Competitive landscape and next milestones

The EGFR-mutant NSCLC field is one of the most competitive in oncology. Approved first- and second-generation EGFR tyrosine kinase inhibitors largely address classical mutations, and osimertinib (AstraZeneca's third-generation agent) dominates the classical mutation setting. Non-classical mutations, however, have proved harder to treat with existing agents, leaving a recognised gap that several fourth-generation programmes are attempting to fill. Silevertinib's brain-penetrant design and its coverage of more than 50 non-classical variants, including the PACC class, represent its principal differentiating claim, though pivotal data will be needed before comparative conclusions can be drawn.

Beyond NSCLC, Black Diamond has initiated enrolment in a randomised Phase 2 trial of silevertinib combined with temozolomide in newly diagnosed EGFRvIII-positive glioblastoma, with the randomised portion expected to begin in the fourth quarter of 2026. The company ended the second quarter with $110.5 million in cash, cash equivalents and investments, down from $128.7 million at year-end 2025, and said this is sufficient to fund operations into the second half of 2028. Quarterly net cash burn was $8.0 million in Q2 2026, modestly below the $9.2 million reported in Q2 2025, reflecting the maturing NSCLC trial offset by GBM start-up costs.