Black Diamond Therapeutics Reports Phase 2 Data Showing Strong Anti-tumor Activity of BDTX-1535 in Recurrent EGFRm NSCLC with Various Resistance Mutations

Black Diamond Therapeutics, Inc., a clinical-stage oncology company, has revealed promising initial data from its Phase 2 trial of BDTX-1535, targeting patients with relapsed or refractory epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This novel therapy aims to address resistance issues arising in patients treated with osimertinib, a commonly used drug for EGFR-mutant NSCLC.

Chief Medical Officer, Dr. Sergey Yurasov, noted the significant potential of BDTX-1535 to offer durable responses for patients who have developed resistance to osimertinib. Dr. Danny Nguyen from the City of Hope emphasized the urgent need for effective and well-tolerated oral therapies for patients with recurrent EGFR-mutant NSCLC, given the limited benefits and high toxicity associated with chemotherapy.

The Phase 2 trial, initiated in August 2023, involves patients with non-classical EGFR mutations (NCMs) and those with C797S resistance mutations. The study's safety assessment and dose selection were based on data from the first 40 patients, who received either 100 mg or 200 mg doses of BDTX-1535 daily. Preliminary response rates and durability were assessed in 27 patients receiving 200 mg, with a data cutoff on August 17, 2024. Out of 22 response-evaluable patients, 19 had known osimertinib resistance mutations, and the preliminary objective response rate (ORR) was 42%.

Key findings from the trial include:
- A daily dose of 200 mg has been selected for further pivotal clinical development.
- The 200 mg dose demonstrated a favorable tolerability profile, with the majority of adverse events being mild or moderate. No new safety signals were observed.
- The most common treatment-related adverse events were rash (70%) and diarrhea (35%). There were two cases of grade 3 rash, but no grade 4 rash or grade 3/4 diarrhea cases were reported.
- Among the 19 patients with known osimertinib resistance mutations, eight achieved a response (42%), including five with a confirmed partial response (PR) and one patient who progressed to an unconfirmed complete response (CR) at eight months.
- Encouraging durability was observed, with the first three patients showing a duration of response (DOR) of approximately eight months or more. Fourteen out of the 19 patients remain on treatment, with a mean follow-up time of 4.7 months.

Mark Velleca, Chief Executive Officer of Black Diamond Therapeutics, expressed satisfaction with the Phase 2 results, which align with prior Phase 1 findings. Velleca highlighted the potential for BDTX-1535 to deliver robust clinical benefits in the first-line setting and shared plans to disclose initial results from the first-line cohort in Q1 2025. The company also aims to outline potential registration pathways based on feedback from the FDA.

BDTX-1535 is described as an oral, brain-penetrant MasterKey inhibitor designed to target a wide range of oncogenic EGFR mutations in NSCLC. This fourth-generation tyrosine kinase inhibitor has shown the ability to inhibit more than 50 mutations, including those seen in glioblastoma (GBM). The company is also conducting a "window of opportunity" trial for patients with GBM.

Black Diamond Therapeutics continues to advance its clinical-stage programs, aiming to address a broad spectrum of genetically defined tumors and overcome resistance mechanisms, with a focus on minimizing toxicity and achieving effectiveness in treating central nervous system diseases.