Black Diamond Therapeutics, Inc. announced topline results from the dose escalation portion of the Phase 1 clinical trial of BDTX-1535 in patients with recurrent glioblastoma (GBM) who expressed epidermal growth factor receptor (EGFR) alterations at the time of their initial diagnosis. BDTX-1535, a fourth-generation, brain-penetrant, covalent EGFR inhibitor, is under investigation in a Phase 1 clinical trial for the treatment of patients with non-small cell lung cancer (NSCLC) or GBM. Clinical data as of November 2023 reflect 27 patients with recurrent GBM who received a range of doses spanning 15mg to 400mg once daily (QD) in the dose escalation cohort.

Combined pharmacokinetic (PK) and safety data from these 27 patients with GBM and 27 patients with NSCLC were previously presented on October 14, 2023 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. No new safety signals were observed; adverse events were consistent with the EGFR tyrosine kinase inhibitor (TKIs) class of drugs, including primarily Grade 1 and 2 diarrhea and rash. Patients with NSCLC dosed at 100mg QD or greater demonstrated confirmed partial responses in lung lesions and CNS metastases.

Key enrollment and inclusion factors: Of the 27 patients with recurrent GBM, 22 were started at or escalated to a dose of 100mg QD or greater and reached at least one post baseline tumor assessment. Patients were heavily pretreated, with a median of 2 prior lines of therapy (range 1-4). All patients except one had received prior temozolomide.

Other prior treatments included chemotherapy, bevacizumab, checkpoint inhibitors or investigational agents. Patients were required to have EGFR alterations at the time of diagnosis, but EGFR status was not known at time of treatment with BDTX-1535 as biopsies are not commonly performed for recurrent disease. Key results: Of the 22 patients evaluable for efficacy, 3 patients were on therapy longer than 10 months, 1 patient longer than 6 months, and 5 patients longer than 4 months.

Historical progression-free survival (PFS) in this population is in the range of 2-4 months. The patient on therapy the longest remains on BDTX-1535 at 100mg QD for over 15 months with prolonged disease stabilization. This patient had previously progressed after 3 months of temozolomide treatment.

Of the 19 patients with measurable disease by Response Assessment in Neuro-Oncology (RANO) criteria, 1 patient achieved a confirmed partial response (PR) and 8 patients experienced stable disease (SD). The patient with the PR stayed on treatment for longer than 4 months at 200 mg QD. Black Diamond plans to submit results from the dose escalation GBM cohort for presentation at a medical meeting in the second quarter of 2024.

Enrollment is ongoing in a ?window of opportunity? clinical trial of BDTX-1535 in second-line patients with high-grade glioma. The trial (NCT06072586) is sponsored by the Ivy Brain Tumor Center in Phoenix, Arizona and is enrolling patients prior to a planned resection in order to assess PK and pharmacodynamics (PD) in brain tissue.

Patients achieving adequate drug levels in the gadolinium non-enhancing regions of the tumor will continue with treatment following surgery. The trial will enroll up to 22 patients, and clinical data is expected in the second quarter of 2024.