Early Silevertinib Data Lead to Phase 2 Trial Development

Initial data from a phase 2 (NCT05256290) clinical trial show that silevertinib yields robust antitumor activity and encouraging central nervous system (CNS) responses in patients with non–small cell lung cancer (NSCLC) harboring nonclassical epidermal growth factor receptor (EGFR) mutations (NCMs).^1,2

These encouraging results will help shape a randomized phase 2 trial of silevertinib in patients with newly diagnosed glioblastoma (GBM).

“We are pleased to share these initial data in frontline NSCLC patients showing silevertinib’s activity against a broad spectrum of 35 distinct [NCM] EGFR,” said Mark Velleca, MD, PhD, president and CEO of Black Diamond Therapeutics, in a news release. “We are particularly encouraged by the CNS activity of silevertinib in treating patients [with NSCLC and] brain metastases, as published data clearly demonstrate that CNS metastases are a key factor in early disease progression for patients [with NCM NSCLC] treated with second- and third-generation EGFR-[tyrosine kinase inhibitors]. We also believe that silevertinib is uniquely positioned as a potential treatment for patients with newly diagnosed EGFR-altered GBM, and plan to initiate a randomized phase 2 trial in the first half of 2026, while PFS data mature in our phase 2 NSCLC study and we continue our partnering discussions.”

Of the 43 total patients, 25 have confirmed partial responses and 1 has a confirmed complete response. The objective response rate (ORR) is 60%. The CNS ORR is 86%. The disease control rate is 91%. There are currently 29 patients still receiving treatment, with the longest duration being > 19 months.

No new safety signals have been observed. Adverse events (AEs) experienced by a majority of patients include rash, stomatitis, diarrhea, and paronychia. AEs were managed with standard supportive care and dose interruptions/reductions without compromising response depth or durability to date.

There are currently43 patients enrolled in the study with frontline NSCLC harboring a broad spectrum of 35 distinct NCM EGFR, including 16 patients with brain metastases (7 of whom had measurable CNS target lesions).

All patients enrolled received 200 mg oral daily dose of silevertinib. Efficacy and safety were assessed at the November 3, 2025 data cutoff date with a median follow-up of 7.2 months. This is an ongoing study.

“These highly encouraging data speak to the potential of silevertinib to be the treatment of choice for frontline patients [with NSCLC] with the full spectrum of [NCM] EGFR,” said Sergey Yurasov, MD, PhD, Black Diamond’s chief medical officer, in the news release. “We are struck by the compelling CNS response rate, which may translate to prolonged durability of response for patients with CNS metastases. Based on these data, and promising phase 0/1 and phase 1 GBM results, we are preparing to initiate a randomized phase 2 trial of silevertinib in newly diagnosed patients [with GBM], one of the highest unmet needs in oncology.”

Phase 2 Plans

Black Diamond intends to initiate the randomized phase 2 trial in the first half of 2026 with preliminary data expected in 2028.¹

The trial has an expected enrollment of approximately 150 patients with newly diagnosed GBM. Patients will be randomized to receive temozolomide (TMZ) in the control arm or silevertinib plus TMZ in the experimental arm.

The initial focus of the trial will be on EGFR8-positive patients (approximately 30% of GBM) who are MGMT-negative (unmethylated). Randomization and treatment will begin after patients have had their surgical resection and radiation. The primary end point of the trial will be progression-free survival with an interim analysis; the secondary end point will be overall survival.

REFERENCES

1.Black Diamond Therapeutics announces preliminary phase 2 data for silevertinib in 1L NSCLC and plans for a phase 2 trial of silevertinib in GBM. News release. Black Diamond Therapeutics. Published and accessed December 3, 2025. https://tinyurl.com/5n8y7anw

2.Phase 1/2 study of silevertinib (BDTX-1535) in patients with glioblastoma or non-small cell lung cancer with EGFR mutations. ClinicalTrials.gov. Updated July 11, 2025. Accessed December 3, 2025. https://clinicaltrials.gov/study/NCT05256290