Black Diamond presents data from Phase 1 dose escalation trial of BDTX-1535

Black Diamond Therapeutics presented additional data from the Phase 1 dose escalation trial of BDTX-1535 in patients with recurrent glioblastoma, and initial data from a phase 0/1 “trigger” investigator-sponsored trial at the American Society of Clinical Oncology Annual Meeting. Clinical data from these trials in patients with recurrent GBM demonstrated brain penetrance of BDTX-1535, as well as safety and tolerability data similar to what has been previously described for patients with non-small cell lung cancer. In addition, the Phase 1 trial demonstrated encouraging anti-tumor activity and duration of treatment for patients with previously treated GBM. In the poster titled “Phase 1 Study of BDTX-1535, an Oral 4th Generation Covalent EGFR Inhibitor, in Patients with Recurrent Glioblastoma: Dose Escalation Results,” patients with EGFR alterations at initial diagnosis were enrolled upon recurrence. Patients received increasing doses of BDTX-1535 in 21-day cycles to assess safety/tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity. As of the data cutoff date of January 20, 2024, safety/tolerability was consistent with BDTX-1535 clinical data in NSCLC previously presented in October 2023 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Treatment-related adverse events were primarily mild to moderate. No grade 3 TRAEs were reported at doses of BDTX-1535 less than or equal to100 mg/day, one grade 3 rash was observed at 200 mg, and no grade 4/5 TRAEs were observed. Among 19 efficacy evaluable patients, several experienced stable disease with promising durability One confirmed partial response was observed and eight patients experienced stable disease. Five patients remained on BDTX-1535 treatment for greater than or equal to4 months, 1 patient for greater than or equal to6 months, and 3 patients for greater than or equal to10 months. Longest duration of treatment was a patient who remained on therapy beyond 16 months. Longer duration of treatment with BDTX-1535 appeared to be associated with a shorter duration of prior treatment with temozolomide. A second poster titled “A Phase 0/1 ‘Trigger’ Trial of BDTX-1535 in Recurrent High-Grade Glioma Patients with EGFR Alterations or Fusions,” is an investigator-sponsored trial conducted at the Ivy Brain Tumor Center in Arizona. Patients with recurrent HGG with EGFR alterations and/or fusions at initial diagnosis were dosed with either 200mg BDTX-1535 daily for five days prior to brain tumor resection or 400mg administered three times per week prior to resection. A pre-specified PK threshold of 4.1nM unbound drug concentration was established, representing exposure that is 5-fold above the IC50 of BDTX-1535 for EGFR alterations and amplifications found in patients with GBM. Initial results from the trial demonstrated that BDTX-1535 exceeded the pre-specified threshold for drug concentration in the brain tumor tissue. In addition, both dosing regimens were generally well tolerated with expected EGFR-mediated side effects As of the data cutoff date of May 3, 2024, nine patients were evaluable. BDTX-1535 generally well tolerated and achieved target drug concentration in tumor tissue. BDTX-1535 was generally well tolerated with no serious adverse events related to BDTX-1535. Eight of nine patients exceeded the PK threshold of 4.1nM unbound drug concentration, with average unbound drug concentration in Gadolinium non-enhancing tumor tissue of 11.9 nM and 18.8nM. BDTX-1535 was associated with suppression of EGFR-mediated signaling as determined by several pharmacodynamic markers. Patients achieving the PK threshold were enrolled in the post-resection component of the study with an update expected in the fourth quarter of 2024.