# Silevertinib heads for a Phase 3 trial built around lung cancer that has spread to the brain - Published: 2026-11-10 (updated 2026-11-10) - Author: [Healthcare News](https://healthcarenews.io/author/healthcarenews-io.md) - Topics: [News](https://healthcarenews.io/news.md) - About: [Black Diamond Therapeutics](https://blackdiamondtherapeutics.com/) - Based on: [Black Diamond Therapeutics press release via GlobeNewswire, November 10, 2026](https://www.globenewswire.com/news-release/2026/11/10/3399281/0/en/black-diamond-therapeutics-announces-positive-updated-silevertinib-phase-2-results-fda-feedback-supporting-a-clear-path-to-potential-registration-in-1l-egfr-ncm-nsclc-and-provides-.html) - Based on: [Rangachari et al., Brain metastases in patients with EGFR-mutated or ALK-rearranged NSCLC, Lung Cancer (2015)](https://pubmed.ncbi.nlm.nih.gov/25682925/) - Based on: [U.S. FDA, Accelerated Approval Program](https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program) - Based on: [ClinicalTrials.gov, NCT05256290](https://clinicaltrials.gov/study/NCT05256290) - Source: https://healthcarenews.io/news/silevertinib-phase-3-trial-egfr-lung-cancer-brain/ - Publication: Healthcare News - Publisher: Connectively (Terkel, Inc.) - Editorial policy: https://healthcarenews.io/editorial-policy/ - AI use: Connectively's automated system wrote this article with AI from a press release issued by Black Diamond Therapeutics on November 10, 2026, linked under Sources. Statements about the company and its products are the company's. The illustration was generated with AI. The article was assembled and published automatically, without an editor's review. Report errors to corrections@connectively.us. Black Diamond Therapeutics plans a silevertinib Phase 3 trial in 2027 for newly diagnosed lung cancer patients with uncommon EGFR mutations whose disease has reached the brain. The Cambridge, Mass. company said on November 10, 2026 that an FDA meeting backed a route to accelerated approval measured by tumor shrinkage in the brain. ## Key points - Black Diamond says its End of Phase 2 meeting with the FDA took place on October 1, 2026, and supports a Phase 3 program in frontline NSCLC with non-classical EGFR mutations. - The planned Phase 3 trial would randomize 300 patients with untreated brain metastases 1:1 to silevertinib 150 mg once daily or the physician's choice of osimertinib or afatinib, starting as soon as the second quarter of 2027. - In updated Phase 2 data from 43 frontline patients, the company reports a 60% overall response rate and a median progression-free survival of 15.0 months. - Among patients with untreated brain metastases evaluable by RANO-BM, the company reports an 86% CNS response rate. - Black Diamond had $102.0 million in cash, cash equivalents and investments on September 30, 2026, which it expects to fund operations into the second half of 2028. ## Why does the brain matter so much in EGFR lung cancer? The brain is where EGFR-mutant lung cancer often spreads, and it stays a risk for years after diagnosis. A Beth Israel Deaconess study of 86 patients with EGFR-mutated NSCLC found brain metastases in 24.4% at diagnosis of advanced disease, and in 46.7% of patients still alive three years later ([Rangachari et al., Lung Cancer, 2015](https://pubmed.ncbi.nlm.nih.gov/25682925/)). The authors called the central nervous system an important unmet need in personalized lung cancer care. Most EGFR mutations are "classical" ones (exon 19 deletions and L858R). Black Diamond says patients with non-classical mutations make up about 25% of the frontline EGFR-mutant population, and its drug is designed to cross into the brain and hit more than 50 of those less common mutations. > Brain is the most common site of distant metastasis for patients with EGFR-mutant NSCLC — Sergey Yurasov, M.D., Ph.D., Chief Medical Officer, Black Diamond Therapeutics ## What will the silevertinib Phase 3 trial test? The silevertinib Phase 3 trial is designed to support potential accelerated approval on brain response and full approval on systemic progression-free survival. According to the company, the primary endpoints are CNS response rate by RANO-BM and systemic PFS by RECIST 1.1, both read by blinded independent central review. The company says the FDA also asked it to show that systemic response rates are similar to the control arm and that overall survival is not worse. Before the Phase 3 opens, the agency wants safety data from enough patients on the 150 mg dose, which a 20-patient cohort of the Phase 2 trial is now enrolling. The planned design, as the company describes it: | Part of the trial | Patients | Treatment | |---|---|---| | Randomized arm | 300 with untreated brain metastases | Silevertinib 150 mg once daily vs. osimertinib or afatinib | | Single-arm cohort | 80 without brain metastases | Silevertinib | | Single-arm cohort | 20 with leptomeningeal disease | Silevertinib | Assuming a second-quarter 2027 start, the company expects preliminary data in 2028. Under the [FDA's Accelerated Approval Program](https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program), a drug for a serious condition can be approved on a surrogate endpoint thought to predict clinical benefit, with confirmatory studies still required for traditional approval. > This trial design offers a differentiated path to potential accelerated approval in EGFR-NCM patients, who represent about 25% of the frontline EGFR mutant patient population. — Mark Velleca, M.D., Ph.D., President and Chief Executive Officer, Black Diamond Therapeutics ## What did the updated Phase 2 data show? Black Diamond reports that silevertinib shrank tumors in most frontline patients, with the longest progression-free survival in those without brain metastases. The trial is registered on ClinicalTrials.gov as [NCT05256290](https://clinicaltrials.gov/study/NCT05256290). As of an October 7, 2026 data cutoff and a median follow-up of 15.9 months, the company reports: - All 43 patients: 60% overall response rate, 93% disease control rate and a median PFS of 15.0 months, with 18 patients still on therapy. - Patients with untreated brain metastases (16 enrolled, 7 evaluable by RANO-BM): 86% CNS response rate and a systemic median PFS of 12.2 months. - Patients without brain metastases (24): a median PFS of 23.5 months, with no patients progressing in the brain. The company says no new safety signals were seen. Alex Spira, a clinical investigator on the trial, said no frontline patient on silevertinib has developed new brain metastases. ## Our analysis: what this means for lung cancer care For oncologists treating EGFR-mutant lung cancer, the trial puts brain response at the center of how a frontline drug for uncommon mutations could reach the market. If it opens as planned, newly diagnosed patients with non-classical mutations and brain metastases would gain a randomized trial built around their disease. For more on cancer programs moving toward the regulator, see our report on an [alpha therapy that set FDA talks for 2027](https://healthcarenews.io/news/lead-212-alpha-therapy-nets-fda-talks-2027/) and on a [blood test for ovarian cancer precursors](https://healthcarenews.io/news/ovarian-cancer-blood-test-tu-stroma-stic/). ## Frequently asked questions ### Who would be eligible for the silevertinib Phase 3 trial? Black Diamond says the randomized part would enroll treatment-naive patients with locally advanced or metastatic NSCLC, a non-classical EGFR mutation and untreated brain metastases. Separate cohorts would take patients without brain metastases and patients with leptomeningeal disease. ### What drugs is silevertinib being compared against? In the planned trial, the control arm is the physician's choice of [osimertinib](https://en.wikipedia.org/wiki/Osimertinib) or [afatinib](https://en.wikipedia.org/wiki/Afatinib), two approved EGFR inhibitors. ### Is silevertinib approved? No. Silevertinib is an investigational oral drug that has been given to over 200 patients with EGFR-mutant NSCLC or EGFR-altered glioblastoma, according to the company. ### Is silevertinib being studied in brain tumors too? Yes. The company says a randomized Phase 2 trial in newly diagnosed EGFRvIII-positive glioblastoma dosed its first patient in the fourth quarter of 2026 ([NCT07326566](https://clinicaltrials.gov/study/NCT07326566)), with interim PFS data expected in the first half of 2028. ### What is Black Diamond's stock ticker? Black Diamond Therapeutics trades on Nasdaq under the symbol BDTX. ## Sources - [Press release from Black Diamond Therapeutics via GlobeNewswire, November 10, 2026](https://www.globenewswire.com/news-release/2026/11/10/3399281/0/en/black-diamond-therapeutics-announces-positive-updated-silevertinib-phase-2-results-fda-feedback-supporting-a-clear-path-to-potential-registration-in-1l-egfr-ncm-nsclc-and-provides-.html) - [Rangachari D, et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer, 2015 (PubMed)](https://pubmed.ncbi.nlm.nih.gov/25682925/) - [U.S. Food and Drug Administration, Accelerated Approval Program](https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program) - [ClinicalTrials.gov, NCT05256290: Phase 1/2 study of silevertinib in glioblastoma or NSCLC with EGFR mutations](https://clinicaltrials.gov/study/NCT05256290) - [Black Diamond Therapeutics, executive team](https://blackdiamondtherapeutics.com/about/executive-team)