Results from Phase 1 dose escalation trial of BDTX-1535 in GBM patients demonstrated a favorable safety and tolerability profile, and encouraging anti-tumor activity and duration of treatment
Initial data from Phase 0/1 “trigger” (“window of opportunity”) investigator-sponsored trial demonstrated BDTX-1535 achieved clinically meaningful drug levels in brain tumor tissue
“The Phase 1 dose escalation results in patients with recurrent GBM show promising duration of treatment beyond two to four months typically expected in the recurrent setting, along with good safety and tolerability at therapeutic doses,” said
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 (PK), pharmacodynamics (PD) and preliminary anti-tumor activity. As of the data cutoff date of
Safety/tolerability was consistent with BDTX-1535 clinical data in NSCLC previously presented in
- Treatment-related adverse events (TRAEs) were primarily mild to moderate; the most common events included rash, diarrhea, stomatitis, paronychia, nausea, and fatigue.
- No grade 3 TRAEs were reported at doses of BDTX-1535 ≤100 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 ≥4 months, 1 patient for ≥6 months, and 3 patients for ≥10 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 (HGG) Patients with EGFR Alterations or Fusions,” is an investigator-sponsored trial conducted at the Ivy Brain Tumor Center in
“We are very pleased with these initial results from our study showing that BDTX-1535 achieves levels in brain tumor tissue needed to observe a therapeutic effect,” said
As of the data cutoff date of
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 (88.9%) patients exceeded the PK threshold of 4.1nM unbound drug concentration, with average unbound drug concentration in Gadolinium (Gd) non-enhancing tumor tissue of 11.9 nM (for the 200mg dose) and 18.8nM (for the 400mg dose).
- 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.
About BDTX-1535
BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), including classical driver mutations, non-classical driver mutations, and the acquired resistance C797S mutation. BDTX-1535 is a fourth-generation tyrosine kinase inhibitor (TKI) that potently inhibits, based on preclinical data, more than 50 oncogenic EGFR mutations expressed across a diverse group of patients with NSCLC in multiple lines of therapy. Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) and avoids paradoxical activation observed with earlier generation reversible TKIs. A “window of opportunity” trial of BDTX-1535 in patients with GBM is ongoing (NCT06072586) and a Phase 2 trial is ongoing in patients with NSCLC (NCT05256290).
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Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: the continued development and advancement of BDTX-1535, the expected timing for a clinical update on data from the “window of opportunity” clinical trial of BDTX-1535 in recurrent GBM patients, and the potential of BDTX-1535 to benefit patients with GBM in an earlier line of treatment. Any forward-looking statements in this statement are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include those risks and uncertainties set forth in its Annual Report on Form 10-K for the year ended
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