Black Diamond advances in brain cancer

Black Diamond Therapeutics told investors in December that its lead EGFR inhibitor, silevertinib, was showing activity in lung cancer, an indication the company prioritised in early 2025. But moving towards approval would require a pivotal trial it could not afford to run alone, and the company has not found a partner yet.

Instead, the company said that it will run a pivotal trial in glioblastoma, and now this has gone live on clinicaltrials.gov. Its new listing confirms a planned April start date, as well as the fact that it will be conducted in two parts, something that could be important given Black Diamond's funding requirement. 

Unmethylated MGMT & EGFRvIII

The glioblastoma study is formally a phase 2, but it does have a control cohort and survival endpoints. 

An initial safety lead-in will evaluate silevertinib in combination with Temodar in newly diagnosed EGFR-positive glioblastoma patients, with the aim of identifying the optimal dose. The trial will then expand into a randomised phase comparing the combination against Temodar.

That second stage will target a more specific population: newly diagnosed patients with unmethylated MGMT promoter who also harbour the EGFRvIII mutation. Black Diamond estimates that this mutation is present in roughly 30% of glioblastoma cases, irrespective of MGMT methylation status.

Overall, the study is expected to enrol around 150 patients. Progression-free survival will be the primary endpoint, and readout is expected in 2028.

Black Diamond is pointing to early but limited clinical evidence to support the move of silevertinib into glioblastoma. 

In a phase 1 study in solid tumours, one of 19 glioblastoma patients treated with the combination achieved a confirmed partial response, while eight experienced stable disease, with most of the nine subjects remaining on treatment for more than four months. The company also reported that no grade 4 or 5 adverse events were observed.

Whether those early signals translate into something meaningful in the front-line setting and justify prioritising the indication over lung cancer will become clearer only as the registrational study progresses. The company's decision to go after glioblastoma was greeted with a 20% share price fall, and the stock hasn't recovered since.

Selected pivotal trials in first-line GBM

Source: OncologyPipeline.