Black Diamond Therapeutics Showcases Promising BDTX-1535 Data in Recurrent Glioblastoma at 2024 ASCO Annual Meeting

Black Diamond Therapeutics, Inc. (BDTX) has revealed promising findings from their Phase 1 dose escalation trial of BDTX-1535, an innovative treatment for glioblastoma (GBM). The data, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, shows that BDTX-1535 not only penetrates brain tumors effectively but also demonstrates encouraging safety and tolerability, alongside notable anti-tumor activity.

The Phase 1 trial involved patients with recurrent GBM who had previously undergone treatments. Participants received escalating doses of BDTX-1535 in 21-day cycles. The trial aimed to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor efficacy. As of January 20, 2024, the results were promising. The treatment-related adverse events (TRAEs) were mainly mild to moderate, with the most common being rash, diarrhea, stomatitis, paronychia, nausea, and fatigue. Significant adverse events were rare; no grade 3 TRAEs were reported for doses of BDTX-1535 up to 100 mg/day, with only one grade 3 rash observed at 200 mg.

Out of 19 evaluable patients, several exhibited stable disease, with one confirmed partial response. Notably, five patients continued BDTX-1535 treatment for over four months, with one patient remaining on the therapy for more than 16 months. The data suggests that a longer duration of BDTX-1535 treatment may be linked to a shorter prior treatment period with temozolomide.

In a parallel investigator-sponsored Phase 0/1 “trigger” trial at the Ivy Brain Tumor Center, patients with high-grade glioma (HGG) and EGFR alterations received either 200 mg of BDTX-1535 daily for five days or 400 mg three times a week before undergoing tumor resection. The goal was to achieve a pre-specified PK threshold of 4.1 nM unbound drug concentration in the brain tumor tissue. Results indicated that BDTX-1535 surpassed this threshold, with average concentrations of 11.9 nM for the 200 mg dose and 18.8 nM for the 400 mg dose. The drug was generally well tolerated, with no serious BDTX-1535-related adverse events reported as of May 3, 2024. Furthermore, BDTX-1535 successfully suppressed EGFR-mediated signaling, as evidenced by several pharmacodynamic markers.

These findings are encouraging for the potential use of BDTX-1535 in treating GBM, particularly in newly diagnosed patients with confirmed EGFR mutations. Dr. Nader Sanai, the Director of the Ivy Brain Tumor Center, expressed optimism, noting the drug's ability to reach therapeutic levels in brain tumor tissue, which could justify further trials.

BDTX-1535 is a fourth-generation covalent EGFR inhibitor, designed to target a wide range of oncogenic EGFR mutations in non-small cell lung cancer (NSCLC) and GBM. It aims to address classical and non-classical driver mutations, as well as the acquired resistance C797S mutation. Preclinical data suggest BDTX-1535 effectively inhibits over 50 oncogenic EGFR mutations, providing a promising therapeutic avenue for diverse patient groups.

Black Diamond Therapeutics focuses on developing MasterKey therapies that target oncogenic mutations. Their approach aims to overcome resistance, minimize toxicities, and effectively penetrate the central nervous system. The company is advancing two primary programs: BDTX-1535 for EGFR mutant NSCLC and GBM, and BDTX-4933 for RAF mutations in solid tumors.

The promising results from these trials highlight BDTX-1535’s potential as a significant advancement in the treatment of GBM and warrant further investigation in subsequent clinical studies.