Black Diamond Therapeutics Presents Dose Escalation Data Demonstrating Durable Responses in Patients with NSCLC from Phase 1 Trial of BDTX-1535
October 14 2023 - 12:30PM
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:
- 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.
- 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.
- 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.
- 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.
- 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 prevalent on-target resistance mutation, co-occurring with an
increasingly heterogeneous set of other EGFR-acquired
resistance mutations, intrinsic drivers, and classical drivers,
highlighting the need for an agent like BDTX-1535 to address the
complex combination of mutations. We look forward to results from
the dose expansion cohorts in patients with NSCLC in 2024 and our
End of Phase 1 meeting with the FDA later this year.”
Black Diamond also presented two additional
posters outlining the study design of the ongoing Phase 1 clinical
trial of BDTX-1535 in NSCLC and preclinical data for BDTX-4933, a
brain-penetrant MasterKey RAF inhibitor targeting KRAS, NRAS and
BRAF alterations in solid tumors. Key preclinical findings from the
BDTX-4933 presentation include:
- BDTX-4933 potently and selectively
inhibited the proliferation of tumor cells expressing a range of
KRAS, NRAS and BRAF mutations in cell lines, suggesting potential
best-in-class potency compared to other RAF inhibitors.
- BDTX-4933 demonstrated strong
anti-tumor activity and regression across cell line and
patient-derived xenograft models expressing several MAPK pathway
mutations, including KRAS G12D, KRAS G12V, and KRAS G13C mutant
NSCLC models.
- BDTX-4933 exhibited high central
nervous system (CNS) exposure leading to dose-dependent tumor
growth inhibition and survival benefit in mice implanted
intracranially with xenograft BRAF mutant tumors.
Black Diamond initiated a Phase 1 clinical trial
for BDTX-4933 with emphasis on KRAS mutant NSCLC in the second
quarter of 2023.
About BDTX-1535BDTX-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 intrinsic 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, greater than 50
oncogenic EGFR mutations and alterations 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
multiforme (GBM) and avoids paradoxical activation observed with
earlier generation reversible TKIs. The ongoing BDTX-1535 Phase 1
clinical trial is currently in dose expansion for NSCLC and dose
escalation for GBM (NCT05256290).
About BDTX-4933BDTX-4933 is an
oral, brain-penetrant RAF MasterKey inhibitor designed to target
oncogenic alterations in KRAS, NRAS and BRAF, while also avoiding
paradoxical activation. In preclinical studies, BDTX-4933 has
demonstrated a potential best-in-class profile, showing potent
target engagement, inhibition of MAPK signaling and strong
anti-tumor activity/tumor regression across tumor models driven by
either KRAS, NRAS or BRAF mutations and alterations. BDTX-4933 also
exhibits high central nervous system (CNS) exposure leading to
dose-dependent tumor growth inhibition and a survival benefit in an
intracranial tumor model harboring oncogenic BRAF mutation. The
ongoing BDTX-4933 Phase 1 clinical trial is currently in dose
escalation with emphasis on KRAS mutant NSCLC patients
(NCT05786924).
About Black Diamond
TherapeuticsBlack 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 on-target/wild-type mediated toxicities, and
be brain-penetrant to treat CNS metastases. 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
StatementsStatements 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
clinical updates on the dose expansion cohorts of BDTX-1535 in
NSCLC patients and on dose escalation data for BDTX-1535 in
recurrent GBM patients, the timing of meeting with regulatory
agencies, and the potential of BDTX-1535 to address an unmet
medical need of patients with EGFR-mutant NSCLC. 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
Julie Seidel, Stern Investor
Relationsinvestors@bdtx.com
For Media:media@bdtx.com
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