On December 3, 2025 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, reported topline data from its Phase 2 trial of silevertinib in frontline (1L) non-small cell lung cancer (NSCLC) patients with non-classical epidermal growth factor receptor (EGFR) mutations (NCMs) and outlined plans for a randomized Phase 2 trial of silevertinib in patients with newly diagnosed glioblastoma (ND GBM).
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"We are pleased to share these initial data in frontline NSCLC patients showing silevertinib’s activity against a broad spectrum of 35 distinct non-classical EGFR mutations," said Mark Velleca, M.D., Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. "We are particularly encouraged by the CNS activity of silevertinib in treating NSCLC patients with brain metastases, as published data clearly demonstrate that CNS metastases are a key factor in early disease progression for NCM NSCLC patients treated with second- and third-generation EGFR-TKIs. 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 matures in our Phase 2 NSCLC study and we continue our partnering discussions."
Silevertinib Phase 2 1L NSCLC Initial Clinical Results and Program Update
43 frontline NSCLC patients harboring a broad spectrum of 35 distinct non-classical EGFR mutations were enrolled, including 16 patients with brain metastases (7 of whom had measurable CNS target lesions). All patients were enrolled at a 200mg oral daily dose of silevertinib. Efficacy and safety were assessed with a November 3, 2025 data cutoff; median follow-up time as of this date was 7.2 months and the study remains ongoing.
Key data highlights include:
For the 43 patients enrolled, preliminary efficacy data is as follows:
25 confirmed partial responses, 1 confirmed complete response
60% Objective Response Rate (ORR by RECIST 1.1)
86% CNS ORR (by RANO-BM)
91% disease control rate (DCR)
Initial duration of treatment data:
29 patients remain on therapy (5/29 after progression), longest ongoing for >19 months
Summary of safety data:
No new safety signals 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
The Company expects to present updated results from the Phase 2 NSCLC trial, including Duration of Response (DOR) and Progression-free Survival (PFS) data in both the recurrent (83 patients) and frontline (43 patients) settings, at a medical meeting in the second quarter of 2026. Black Diamond continues to explore potential partnerships to advance silevertinib into pivotal development.
"These highly encouraging data speak to the potential of silevertinib to be the treatment of choice for frontline NSCLC patients with the full spectrum of non-classical EGFR mutations" said Sergey Yurasov, M.D., Ph.D., Black Diamond’s Chief Medical Officer. "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 GBM patients, one of the highest unmet needs in oncology."
GBM Program Update and Phase 2 Plans
Approximately 50% of patients with glioblastoma (GBM) present with an oncogenic EGFR alteration that can be targeted by silevertinib; each year approximately 7,000 patients in the U.S. are diagnosed with GBM harboring these EGFR alterations.
"Prior attempts to treat EGFR-altered GBM patients have been limited by poor brain penetrance of targeted therapies and/or lack of potency of these therapies on the full spectrum of EGFR alterations" said Elizabeth Buck, Ph.D., Chief Scientific Officer of Black Diamond. "Based on encouraging CNS activity demonstrated by silevertinib across multiple trials, and its preclinical potency on all EGFR alterations found in GBM, we believe that silevertinib has the potential to be the first targeted therapy for these patients."
Black Diamond plans to initiate a randomized Phase 2 trial in newly diagnosed GBM patients in the first half of 2026, with preliminary data expected in 2028.
Key trial highlights include:
Expected to enroll approximately 150 newly diagnosed patients, randomized to receive TMZ (control arm) or silevertinib + TMZ (experimental arm)
Initial focus will be on EGFRvIII-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
Primary endpoint is PFS (RANO by Blinded Independent Committee Review), with an interim analysis; secondary endpoint is overall survival (OS)
Trial will be governed by an Independent Data Monitoring Committee (IDMC)
Updated Financial Guidance
Black Diamond previously reported cash, cash equivalents and investments of approximately $135.5 million as of September 30, 2025, which the Company now believes is sufficient to fund its anticipated operating expenses and capital expenditure requirements into the second half of 2028.
Financial guidance assumes Black Diamond funds the Phase 2 trial of silevertinib in ND GBM and a potential partner funds pivotal development in NSCLC. Financial guidance does not assume receipt of potential development milestones from the Company’s partnership with Servier Pharmaceuticals LLC for BDTX-4933 (now S241656).
Conference Call Information
Black Diamond will host a conference call and webcast on Wednesday, December 3, 2025, at 8:00 AM ET to discuss the preliminary Phase 2 data for silevertinib in 1L NSCLC and plans for a Phase 2 trial of silevertinib in GBM. The webcast may be accessed online here or by visiting the Events page in the Investors section of the Company’s website at www.blackdiamondtherapeutics.com.
A replay of the webcast will be available for 30 days on the Investors section of Black Diamond’s website.
(Press release, Black Diamond Therapeutics, DEC 3, 2025, View Source [SID1234661096])