Black Diamond Therapeutics Announces Initial Dose Escalation Data Demonstrating Anti-Tumor Activity of BDTX-1535 in Non-Small Cell Lung Cancer Patients Across Multiple EGFR Mutation Families
2023年6月27日 - 8:00PM
Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage
precision oncology company developing MasterKey therapies that
target families of oncogenic mutations in patients with genetically
defined cancers, today announced initial clinical data from the
dose escalation portion of the Phase 1 clinical study of BDTX-1535.
BDTX-1535 is an investigational fourth-generation epidermal growth
factor receptor (EGFR) MasterKey inhibitor being developed for the
treatment of non-small cell lung cancer (NSCLC) and glioblastoma
multiforme (GBM). The new data from the dose escalation portion of
the Phase 1 study demonstrated clinical proof of activity of
BDTX-1535 in NSCLC patients harboring both acquired resistance and
intrinsic driver EGFR mutations.
“These initial safety and clinical activity data
support the continued development of BDTX-1535 as a potential first
and best-in-class treatment option for osimertinib-resistant NSCLC
patients. Importantly, BDTX-1535 is the first EGFR TKI to show
radiographic responses across NSCLC patients whose cancers are
driven by diverse mutation families including acquired resistance
mutations after osimertinib therapy, as well as in patients whose
cancers are driven by classical and intrinsic driver mutations,
providing clinical validation for our MasterKey approach of
targeting families of mutations with a single drug,” said Sergey
Yurasov, M.D., Ph.D., Chief Medical Officer of Black Diamond
Therapeutics. “With a favorable tolerability profile in dose
escalation, a long half-life to support once-daily dosing and ease
of administration, we believe that BDTX-1535 has the potential to
become an important treatment option for patients suffering from
EGFR-mutated NSCLC. With these data in hand, we look forward to
working with the FDA to define our recommended Phase 2 dose
selection strategy and, ultimately, discussing a path to potential
accelerated approval in NSCLC patients with newly diagnosed and
recurrent intrinsic and acquired resistance EGFR mutations.”
“Intrinsic and acquired resistance to osimertinib
remains a significant challenge for patients with EGFR-mutant lung
cancers. There is a large unmet need to personalize therapies based
on acquired EGFR resistance mechanisms post treatment with
osimertinib but also an equally important unmet need to address
intrinsic resistance, with a focus on EGFR mutation subtypes that
do worse with current therapies such as EGFR L858R or atypical EGFR
mutations such as EGFR exon 18 mutations. That is why a
fourth-generation EGFR TKI that addresses intrinsic and acquired
resistance by effectively targeting these EGFR alterations -
combined with ease of administration and brain penetrance - may be
an impactful treatment option for patients. I am eager to see
BDTX-1535 continue to advance in the clinic,” said Helen Yu, M.D.,
Associate Attending Physician at Memorial Sloan Kettering Cancer
Center.
BDTX-1535 Phase 1 Study Design
This Phase 1 first-in-human, open-label clinical
trial of BDTX-1535 consists of dose escalation followed by dose
expansion cohorts. The dose escalation part is based on a Bayesian
Optimal Interval adaptive design to evaluate the safety,
pharmacokinetics (PK), and preliminary anti-tumor activity of
BDTX-1535 in adult patients with either advanced/metastatic NSCLC
harboring EGFR mutations with or without central nervous system
(CNS) disease, or recurrent GBM expressing EGFR alterations.
Following the dose escalation portion, the study includes several
disease specific expansion cohorts to assess objective response
rate (ORR), CNS ORR and progression-free survival and further
evaluate safety, tolerability and PK.
Initial Phase 1 Dose Escalation
Data
As of the data cutoff date of May 20, 2023, a total
of 51 patients (24 patients with recurrent EGFR+ NSCLC and 27
patients with recurrent GBM with EGFR alterations) were treated
with BDTX-1535 in the dose-escalation portion of the Phase 1
clinical trial at seven dose levels ranging from 15mg to 400mg
once-daily (QD). NSCLC patients (n=24) were heavily pretreated with
a median of two prior therapies (range 1-9); all patients received
prior treatment with EGFR TKI with the majority receiving
osimertinib (79%) as first- or second-line treatment, 67% of
patients receiving prior chemotherapy, and 42% of patients
receiving prior anti-angiogenesis drug or checkpoint inhibitors.
All glioblastoma patients had a recurrent disease after standard of
care surgery, radiation and chemotherapy. The Company will provide
a clinical update on BDTX-1535 Phase 1 dose escalation data in
recurrent GBM patients in the fourth quarter of 2023.
- The BDTX-1535 PK profile obtained
during dose escalation in NSCLC and GBM patients showed a linear
increase in exposure with an average half-life of approximately 15
hours that supports a daily dosing schedule with sufficient and
sustained steady state target mutation coverage achieved at 100 mg
QD dose level and above.
- BDTX-1535 was generally well
tolerated by NSCLC and GBM patients and the overall safety profile
was consistent with the EGFR tyrosine kinase inhibitor (TKI) class
of drugs. The most common drug-related adverse events were mild to
moderate rash, diarrhea, stomatitis, paronychia, nausea and
fatigue. No patients experienced dose limiting toxicity at 15-200
mg QD doses. One of 15 patients treated at the 300 mg QD dose
experienced dose limiting diarrhea and 5 of 12 patients at the 400
mg QD dose experienced dose limiting toxicity (diarrhea, 2
patients; rash, stomatitis, fatigue and decreased appetite, 1
patient each). No unexpected safety signal was identified during
dose escalation.
- Based on additional data updates as
of June 16, 2023, 5 of 12 NSCLC patients in a subgroup, who had
measurable disease at study start, and underwent post baseline
tumor assessment by RECIST1.1, demonstrated radiographic confirmed
partial response (PR). One additional patient demonstrated
unconfirmed PR awaiting confirmation, while the remaining six
patients had stable disease.
- Confirmed PRs were observed in NSCLC
patients with a wide range of EGFR mutations including classical
and intrinsic driver mutations and acquired C797S resistance
mutation, as well as complex mutations that include a combination
of classical, intrinsic, and acquired resistance mutations.
Radiographic improvement of CNS metastasis was documented in 2
NSCLC patients.
- Based on emerging PK, safety,
tolerability and radiographic response data, enrollment will
commence at the BDTX-1535 200 mg QD dose in two expansion cohorts
of NSCLC patients with acquired resistance or intrinsic driver
mutations who received up to two prior lines of therapy including a
third-generation EGFR TKI. Additional doses may be further
evaluated after review of the totality of dose escalation data
during a meeting with the U.S. Food and Drug Administration (FDA)
later in 2023. The objective of expansion cohorts will be ORR by
RECIST 1.1 and durability of response to support future discussion
with the FDA of a potential accelerated approval path in
EGFR-mutated NSCLC. In addition, BDTX plans to open an expansion
cohort in newly diagnosed NSCLC patients with intrinsic driver
mutations after discussion with the FDA.
Black Diamond anticipates the following key
milestones for BDTX-1535:
- Initiation of the dose expansion
cohorts of NSCLC patients with EGFR acquired resistance and
intrinsic driver mutations after progression on third generation
EGFR TKI with the objective of ORR by RECIST 1.1 in the second half
of 2023
- Presentation of the full BDTX-1535
dose escalation data in NSCLC at a medical conference in the fourth
quarter of 2023
- Meeting with the FDA in the fourth
quarter of 2023 to align on dosing strategy to enable a potential
accelerated approval pathway in NSCLC
- Initiation of an expansion cohort in
newly diagnosed NSCLC patients with intrinsic driver mutations
after discussion with the FDA
- Clinical update on BDTX-1535 Phase 1
dose escalation data in recurrent GBM patients in the fourth
quarter of 2023
Conference Call Information
Black Diamond will host a conference call and
webcast on Tuesday, June 27, 2023, at 8:00 a.m. ET to discuss the
initial results from the Phase 1 dose escalation study of BDTX-1535
in patients with NSCLC. The webcast may be accessed online here or
by visiting the Events page in the Investors section of the
Company’s website at www.blackdiamondtherapeutics.com.
A replay of the webcast will be available for 30
days on the Investors section of Black Diamond’s website.
About Black Diamond
Therapeutics
Black Diamond Therapeutics is a clinical-stage
precision oncology medicine company focused on the development of
MasterKey therapies that target families of oncogenic mutations in
clinically validated targets. Black Diamond leverages a deep
understanding of cancer genetics and onco-protein structure and
function, to discover and develop innovative MasterKey therapies.
The Company’s MasterKey therapies are designed to overcome
resistance, minimize on-target, wild-type mediated toxicities, and
be brain-penetrant to address significant unmet medical needs of
patients with genetically defined cancers. The Company is advancing
a robust pipeline with lead clinical-stage program BDTX-1535,
targeting MasterKey mutations in both EGFR mutant-positive NSCLC
and in GBM, and BDTX-4933, a program targeting RAF MasterKey
mutations in solid tumors, as well as discovery-stage research
programs. The Company’s proprietary MAP drug discovery engine is
designed to allow Black Diamond to analyze population-level genetic
sequencing tumor data and validate MasterKey mutations. 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 BDTX-1535 development program, including
the initiation of the dose expansion cohorts of BDTX-1535 in NSCLC
patients, presentation of the full BDTX-1535 dose escalation data
in NSCLC, a potential accelerated approval pathway for BDTX-1535 in
NSCLC and the upcoming clinical update on BDTX-1535 in recurrent
GBM patients. 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.
ContactsFor Investors:Julie
Seidel, Stern Investor Relations(212)
362-1200investors@bdtx.com
For Media:Kathy
Vincentkathy@kathyvincent.commedia@bdtx.com
Black Diamond Therapeutics (NASDAQ:BDTX)
過去 株価チャート
から 8 2024 まで 9 2024
Black Diamond Therapeutics (NASDAQ:BDTX)
過去 株価チャート
から 9 2023 まで 9 2024