Black Diamond Therapeutics plans 300‑patient silevertinib trial after FDA feedback
The 86 per cent brain-response rate came from seven evaluable patients; lower-dose safety data are required before Phase 3.
Adrian Kessler
A 300-patient lung-cancer trial could start in 2027 after Black Diamond Therapeutics, Inc. NASDAQBDTX reported updated Phase 2 silevertinib results and FDA feedback on Tuesday. The proposed Phase 3 study would test brain-lesion response for potential accelerated approval, with preliminary data expected in 2028.
The Nov. 10 release reported a 60 per cent overall response rate among 43 previously untreated patients. Median progression-free survival, the time before disease worsens or death, was 15.0 months. Its 95 per cent confidence interval ranged from 11.0 to 23.5 months.
Black Diamond is a small biotechnology company based in Cambridge, Mass., developing medicines for genetically defined cancers.
Nasdaq shares NASDAQBDTX closed at US$1.86 on Nov. 9 at 4:00 p.m. EST, before the announcement. Black Diamond held US$102.0 million in cash, cash equivalents and investments on Sept. 30. Management expects that liquidity to fund operations into the second half of 2028.
The Oct. 7 data cutoff covered patients receiving 200 mg once daily, with median follow-up of 15.9 months. Among 16 patients with untreated brain metastases, seven were evaluable for the 86 per cent brain-response result under RANO-BM imaging criteria. The reported cohort had no control arm, so these results do not establish superiority to existing treatments.
The company reported no new safety signals. Its May 21 update said the rate of treatment-related adverse events above grade 3 fell to 28 per cent following dose reduction.
"Brain is the most common site of distant metastasis for patients with EGFR-mutant NSCLC," Black Diamond chief medical officer Sergey Yurasov said in the release.
Lower-Dose Safety Data Must Precede Phase 3
According to Black Diamond's account of its Oct. 1 meeting, the FDA provided feedback on potential accelerated approval using brain-response rates and full approval using progression-free survival. Brain responses would use RANO-BM criteria and systemic progression RECIST 1.1, both assessed through blinded independent central review.
The company said the FDA also requires evaluation of systemic response and overall survival. That assessment must show similar systemic response and no evidence of worse survival than the control arm.
The proposed trial would randomly assign patients equally to silevertinib or a physician's choice of osimertinib or afatinib. Silevertinib would be given at 150 mg daily, below the dose used in the reported efficacy cohort.
The FDA requires safety data from enough patients at that lower dose before the trial opens, Black Diamond said. An ongoing 20-patient cohort is collecting those data. The broader program would add separate single-arm cohorts for patients without brain metastases and those with leptomeningeal disease.
Read more: Satellos changes BASECAMP trial endpoint after FDA feedback
EGFR Developers Pursue Distinct Patient Groups
Black Diamond's Nov. 10 estimate puts non-classical mutations at about 25 per cent of frontline EGFR-mutant cases. Its planned program excludes classical exon 19 deletions, L858R mutations and exon 20 insertions.
AstraZeneca PLC LONAZN NYSEAZN supplies osimertinib as Tagrisso, one of the proposed control options. AstraZeneca's Sept. 14 update reported results in surgically treated EGFR-mutant lung cancer, a different treatment setting.
ArriVent BioPharma, Inc. NASDAQAVBP reported median progression-free survival of 16.0 months in its June 23, 2025 firmonertinib update for PACC mutations, an uncommon EGFR subgroup. Those historical data come from a separate study and cannot establish a comparative benefit for either drug.
Read more: Lilly reports 14.5-month response duration with olomorasib lung-cancer combination
Operating cash use was US$8.3 million in the quarter ended Sept. 30. That historical spending figure does not establish the cost of the larger pivotal program or guarantee funding through a regulatory decision.
Black Diamond targets the second quarter of 2027 to open the randomized trial, after providing the required lower-dose safety data. If it starts then, the company expects preliminary results in 2028.
