Black Diamond Therapeutics reported updated Phase 2 results for silevertinib, its brain-penetrant fourth-generation EGFR inhibitor, in 43 frontline non-small cell lung cancer patients whose tumours carry non-classical EGFR mutations. At the 200 mg once-daily dose, with median follow-up of 15.9 months, the overall response rate was 60 percent, the disease control rate was 93 percent, and median progression-free survival was 15.0 months. Eighteen patients remained on therapy, the longest for 26.2 months, and the company reported no new safety signals.
The brain data are the centre of the release. Among 16 patients with untreated brain metastases, seven were evaluable by RANO-BM criteria and the central nervous system response rate in that evaluable group was 86 percent, with systemic median progression-free survival of 12.2 months. Among 24 patients without brain metastases at entry, median progression-free survival was 23.5 months and no patient progressed in the brain. The company describes the progression-free survival as double that of currently available EGFR inhibitors; that is a cross-trial comparison from a single-arm study, not a head-to-head result, and the brain response rate rests on seven evaluable patients.
The regulatory news is as material as the data. At an End of Phase 2 meeting on October 1, the FDA supported a Phase 3 programme covering all treatment-naive patients with non-classical EGFR mutations, with a potential accelerated approval based on central nervous system response rate assessed by blinded independent review, and a potential full approval based on progression-free survival. The agency said systemic response rate and overall survival will also need to be evaluated against the control arm, acknowledged the company’s case for the lower 150 mg pivotal dose, and requires safety data from the ongoing 150 mg Cohort 4 before the Phase 3 can open.
The planned Phase 3 would enrol 300 patients with untreated brain metastases, randomised to silevertinib or physician’s choice of osimertinib or afatinib, plus an 80 patient single-arm cohort without brain metastases and a 20 patient leptomeningeal disease cohort. The company targets a start in the second quarter of 2027, with preliminary data in 2028. Non-classical mutations represent about 25 percent of the frontline EGFR-mutant population, according to the company.
Financially, Black Diamond ended the third quarter with 102.0 million dollars in cash, cash equivalents and investments, a net loss of 10.0 million dollars for the quarter against 8.5 million a year earlier, and a stated runway into the second half of 2028. A randomised Phase 2 of silevertinib in newly diagnosed EGFRvIII-positive glioblastoma is also enrolling, with interim progression-free survival data expected in the first half of 2028.