Black Diamond Therapeutics Touts Silevertinib Lung Cancer Data, Eyes FDA Path

Key Points

• Silevertinib showed encouraging Phase 2 lung cancer data, including a 60% objective response rate and a preliminary median progression-free survival of 15.2 months in frontline non-small cell lung cancer patients with non-classical EGFR mutations.
• The drug also posted notable CNS activity, with an 86% confirmed response rate in patients with measurable brain lesions and no reported de novo brain metastases during follow-up.
• Black Diamond plans to seek an FDA meeting soon to discuss the fastest path to approval, while separately advancing silevertinib in a randomized Phase 2 glioblastoma trial; the company ended Q1 with $118 million in cash but said a pivotal lung study would likely require additional financing or a partnership.

Black Diamond Therapeutics NASDAQ: BDTX is positioning its lead oncology drug candidate, silevertinib, as a potential treatment for non-small cell lung cancer patients with non-classical EGFR mutations, Chief Executive Officer Mark Velleca said during a Jefferies fireside chat following the company’s presentations at ASCO.

Velleca described Black Diamond as a “precision small molecule oncology company” and said silevertinib is being evaluated as a potential “first and best-in-class fourth generation EGFR inhibitor.” The drug is in Phase 2 testing for patients with non-small cell lung cancer and glioblastoma.

At ASCO, the company presented data in frontline lung cancer patients and in the recurrent setting. Velleca said the frontline dataset showed a preliminary median progression-free survival, or PFS, of 15.2 months in 43 patients, with more than half of patients still on therapy at a median follow-up of 11.2 months.

Non-Classical EGFR Population

Velleca said about 10,000 patients per year in the United States have non-classical EGFR mutations, representing roughly 25% of the overall EGFR-mutated non-small cell lung cancer market. He said the group includes more than 50 distinct mutations and currently has “no standard of care.”

According to Velleca, physicians commonly treat these patients with chemotherapy, afatinib or off-label osimertinib, but outcomes have generally ranged from about six months to as much as 11 months of PFS in published studies. He contrasted that with patients who have classical EGFR mutations, where PFS is typically in the 14- to 20-month range.

Velleca also said non-classical EGFR patients differ clinically from classical EGFR patients. He said more than one-third have compound mutations, and about 40% have brain metastases at diagnosis, compared with about 20% among patients with classical mutations.

ASCO Data Highlight Response and CNS Activity

The company reported a 60% objective response rate across 43 frontline patients with 33 distinct non-classical EGFR mutations, including compound and PACC mutations. Velleca said the response rate was confirmed under RECIST 1.1 criteria and was consistent across mutation categories, ranging from the high 50% range to the low 70% range.

Velleca said 53% of patients, or 23 of 43, remained on therapy, with the longest patient on treatment for 23.5 months. He said dose reductions from 200 mg to 150 mg, and in some cases to 100 mg, had not sacrificed the depth or durability of responses. He added that many dose reductions occurred during the first cycle, while the deepest responses were typically seen around seven months.

Black Diamond also disclosed circulating tumor DNA findings. Velleca said every evaluable patient with ctDNA showed a substantial reduction in variant allele frequency, with complete clearance in more than 80% of those patients. He said the company views those results as supportive of potentially longer PFS, while noting the dataset remains small.

Velleca emphasized central nervous system activity as the most notable aspect of the ASCO dataset. He said the company observed an 86% confirmed RANO-BM response rate in patients with measurable brain lesions, and that no patient developed de novo brain metastases while on therapy during the reported follow-up period.

“The lack of any de novo brain metastasis, we think bodes well for long-term overall survival in this frontline setting and opens up a really large opportunity to benefit patients in the adjuvant setting,” Velleca said.

Safety and Dose Strategy

Velleca said the company has studied silevertinib across more than 200 patients and has a detailed understanding of its pharmacokinetic profile. He described the drug as dose-linear and said Black Diamond has “very strong conviction” in 150 mg once daily as the go-forward dose.

He said Grade 3 or greater adverse events declined to 28% after dose reductions, and that the company expects a similar rate in the low 30% range when starting patients at 150 mg. Velleca said the adverse events observed were EGFR-mediated, such as rash and diarrhea, and that the company has not seen QTc or liver signals.

Six of 43 patients, or 14%, discontinued treatment due to adverse events. Velleca said those discontinuations occurred early and involved EGFR-mediated events such as rash and diarrhea.

Regulatory Plans and Potential Trial Designs

Velleca said Black Diamond plans to request a meeting with the U.S. Food and Drug Administration shortly and expects the meeting to occur in the third quarter, with feedback in the early fourth quarter. He said the goal is to identify the fastest path to bring silevertinib to patients.

Potential development strategies discussed by Velleca included focusing on patients with CNS disease at diagnosis, where he said current PFS outcomes are about five to six months, or targeting patients with PACC mutations, which he described as resistant to osimertinib. He said the path could include a randomized trial and potentially a single-arm trial, depending on the population and regulatory feedback.

Velleca also said Black Diamond believes its development path could be more streamlined than the FURVENT study, citing silevertinib’s reported breadth across non-classical mutations and CNS activity. He contrasted the company’s 60% overall response rate and 86% CNS response rate with what he described as lower CNS activity in competing data discussed at ASCO.

Glioblastoma Program, Cash and Catalysts

Black Diamond is also advancing silevertinib in glioblastoma. Velleca said the company has started a randomized Phase 2 trial in newly diagnosed patients after surgery and chemoradiation. Patients are being randomized to silevertinib plus standard of care temozolomide versus temozolomide alone.

Velleca said the first cohort has been enrolled. He said PFS in the population is about six months and that a three- to four-month improvement would be taken to regulators. He added that the study includes features that could support conversion to a registrational trial, including PFS by blinded independent central review and monitoring by an independent data monitoring committee. Data are expected in the first half of 2028.

Velleca said Black Diamond ended the first quarter with $118 million in cash and has funding into the second half of 2028, which supports the glioblastoma trial. He said the company would need to raise capital and/or partner for a pivotal lung cancer study. Key catalysts include FDA feedback, additional lung cancer data in the fourth quarter, potential initial overall survival data in late 2027 or the second half of 2027, and glioblastoma data in the first half of 2028.

About Black Diamond Therapeutics NASDAQ: BDTX

Black Diamond Therapeutics, Inc is a precision oncology company focused on the discovery and development of small-molecule therapies that selectively target oncogenic proteins bearing tumor-driving mutations. Leveraging its proprietary Genetic Defined Allosteric (GDA) therapeutic platform, the company aims to identify unique allosteric binding sites in mutant proteins and engineer highly selective inhibitors. Headquartered in Cambridge, Massachusetts, Black Diamond applies structure-based drug design and molecular modeling to advance personalized cancer treatments.

The company's development pipeline includes lead candidate BDTX-189, an allosteric inhibitor of mutant HER2, as well as programs directed at clinically relevant EGFR and KRAS mutations.

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