Black Diamond Therapeutics Announces Topline Results from Phase 1 Dose Escalation Trial of BDTX-1535 in Patients with Recurrent GBM
13 December 2023 - 11:00PM
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 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.
“These initial results in patients with
recurrent GBM are encouraging, as there are no approved therapies
available for those who progress following initial treatment, and
there is strong rationale for a brain penetrant, covalent EGFR
inhibitor such as BDTX-1535 to have a meaningful impact in earlier
lines of therapy,” said Patrick Wen, M.D., Director of The Center
for Neuro-Oncology at Dana-Farber Cancer Institute.
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.
“We believe the ‘window of opportunity’ trial of
BDTX-1535 will provide valuable information on both drug levels in
the brain and clinical activity in second-line patients, and will
inform potential next steps in our development program,” said
Sergey Yurasov, M.D., Ph.D., Chief Medical Officer of Black Diamond
Therapeutics. “More than half of all newly diagnosed GBM patients
express an altered form of EGFR, and preclinical data demonstrate
BDTX-1535 potently inhibits this spectrum of alterations.
Therefore, BDTX-1535 may be optimally suited to benefit first-line
patients.”
About BDTX-1535
BDTX-1535 is an oral, brain-penetrant MasterKey
inhibitor of oncogenic epidermal growth factor receptor (EGFR)
mutation in non-small cell lung cancer (NSCLC), including families
of non-classical driver mutations (e.g., L747P, L718Q), acquired
resistance C797S mutation, and complex mutations. BDTX-1535 is a
fourth generation 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. Dose escalation of
BDTX-1535 in patients with GBM is complete and dose expansion is
currently ongoing in patients with NSCLC (NCT05256290).
About Black Diamond Therapeutics
Black Diamond Therapeutics is a clinical-stage
oncology company focused on the development of MasterKey therapies
that address families of oncogenic mutations in clinically
validated targets. The Company’s MasterKey therapies are designed
to address broad genetically defined patient populations, overcome
resistance, minimize wild-type mediated toxicities, and be
brain-penetrant to treat CNS disease. The Company is advancing two
clinical stage programs: BDTX-1535, a brain-penetrant
fourth-generation EGFR MasterKey inhibitor targeting EGFR mutant
NSCLC and GBM, and BDTX-4933, a brain penetrant RAF MasterKey
inhibitor targeting KRAS, NRAS and BRAF alterations in solid
tumors. For more information, please visit
www.blackdiamondtherapeutics.com.
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, including the Phase 1 clinical trial, the expected
timing for clinical updates on data from the “window of
opportunity” clinical trial of BDTX-1535 in recurrent GBM patients
and presentation of the full BDTX-1535 dose escalation data in GBM,
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
December 31, 2022, filed with the United States Securities and
Exchange Commission and in its subsequent filings filed with the
United States Securities and Exchange Commission. All
forward-looking statements contained in this press release speak
only as of the date on which they were made. The Company undertakes
no obligation to update such statements to reflect events that
occur or circumstances that exist after the date on which they were
made.
Contacts
For Investors:Mario Corso, Head of Investor Relations, Black
Diamond Therapeuticsmcorso@bdtx.com
For Media:media@bdtx.com
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