Initial results from BDTX-1535 dose escalation show durable activity in patients with NSCLC across heterogeneous EGFR mutation subtypes
No new safety or tolerability signal reported across all three active once daily doses of
100mg, 200mg and 300mg
Initial NSCLC expansion cohort data expected in 2024
Initial GBM dose escalation data expected later this year
CAMBRIDGE, Mass. and NEW YORK, Oct. 14, 2023 (GLOBE NEWSWIRE) — Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with genetically defined cancers, today presented results demonstrating encouraging response durability of BDTX-1535 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). BDTX-1535, a fourth-generation, brain-penetrant epidermal growth factor receptor (EGFR) inhibitor, is under investigation in a Phase 1 clinical trial for patients with NSCLC or glioblastoma multiforme (GBM). The NSCLC results were disclosed in a poster presentation on October 14, 2023 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.
The findings expand upon the initial dose escalation results disclosed on June 27, 2023, which showed anti-tumor activity of BDTX-1535 in patients with NSCLC across heterogeneous EGFR mutation subtypes (including acquired resistance C797S mutation, intrinsic driver mutations, e.g., L747P, L718Q, as well as complex mutations). Data shared at the 2023 AACR-NCI-EORTC conference reflects 27 patients with advanced/metastatic NSCLC who received a range of doses spanning 25mg to 400mg once daily. A poster titled “Phase 1 Study of BDTX-1535, an Oral 4th Generation Inhibitor, in Patients with Non-Small Cell Lung Cancer and Glioblastoma: Preliminary Dose Escalation Results” shows that BDTX-1535 achieved:
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Drug exposures providing target coverage. Pharmacokinetic (PK) analyses demonstrated that doses at or above 100mg provide sufficient drug levels to cover all relevant mutations over a 24-hour period following once daily oral administration.
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Favorable emerging safety profile. The majority of adverse events (AEs) at doses of 100mg and 200mg were mild or moderate, and no unexpected safety signals were identified. No dose limiting toxicities (DLTs) were observed at or below 200mg dose level.
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Circulating tumor DNA (ctDNA) clearance. Eradication of targeted variant alleles and significant ctDNA reductions were observed for all NSCLC EGFR mutation subtypes in patients treated across dose levels. ctDNA reduction has been shown to be predictive of clinical response.
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Radiographic responses in patients with NSCLC at starting dose of 100mg or above. Five of the 13 patients with either intrinsic driver, acquired resistance or complex mutations had a confirmed partial response (PR) by RECIST1.1. One patient remains an unconfirmed PR and continues on study with no sign of tumor progression, and six patients have stable disease at doses at or above 100mg once daily. Evidence of reduction in brain metastases was observed, including a patient with more than three prior therapies.
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Durable clinical responses in patients with NSCLC who have had multiple lines of prior therapy. Three responders continue on therapy for greater than six months (two confirmed PRs, one uPR). One patient with confirmed PR remained on therapy for six months. Two additional patients with stable disease continue on therapy for greater than 12 months.
“These results point to a highly active compound that has the potential to fill a substantial unmet need for an oral, well-tolerated precision therapy option in the current NSCLC therapeutic landscape for patients who progressed on a third-generation EGFR inhibitor,” said Helena Yu, M.D., Associate Attending Physician at Memorial Sloan Kettering Cancer Center. “We are most encouraged by the durable responses observed, as they underscore the potential of BDTX-1535 for patients with NSCLC who have progressed on prior tyrosine kinase inhibitors (TKIs).”
Black Diamond is currently enrolling patients in the expansion cohorts evaluating BDTX-1535 at doses of 100mg and 200mg in patients with intrinsic driver and acquired resistance EGFR mutation positive NSCLC assessing objective response rate (ORR) by RECIST 1.1. The Company expects to share initial results from this portion of the study in 2024.
“These dose escalation results underscore that the well-tolerated and durable clinical activity of BDTX-1535 could have important implications for patients with EGFR mutant NSCLC,” said Sergey Yurasov, M.D., Ph.D., Chief Medical Officer of Black Diamond Therapeutics. “As real-world evidence shows, C797S is the most…
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