Zentalis Pharmaceuticals to Present Promising Results from Phase 1 Trial of Azenosertib and Gemcitabine in Relapsed or Refractory Osteosarcoma at 2024 American Society of Clinical Oncology Annual Meeting
May 23 2024 - 5:01PM
Zentalis® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage
biopharmaceutical company discovering and developing clinically
differentiated small molecule therapeutics targeting fundamental
biological pathways of cancers, today announced the presentation of
final results from a Phase 1 trial of azenosertib and gemcitabine
in relapsed or refractory (R/R) osteosarcoma at the 2024 American
Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
“We are pleased to report the final results from
our Phase 1 trial evaluating azenosertib administered with
gemcitabine in patients with relapsed or refractory osteosarcoma,”
said Kimberly Blackwell, M.D., Chief Executive Officer of Zentalis.
“Azenosertib was well tolerated and clinically active in
combination with gemcitabine and a go-forward dose was identified.
Most importantly, the event-free survival results demonstrate a
tripling in the proportion of patients without progression or death
at 18 weeks compared with historical control patients. These
results support studying the combination in patients facing this
aggressive cancer, which we expect will occur in an upcoming
investigator-initiated Phase 2 trial. We also look forward to
presenting additional data on azenosertib in gynecological
malignancies later this year as our development path continues to
progress on track.”
Data Highlights and Conclusions:
- 31 patients were enrolled in the study, of which 31 were
evaluable for safety, 29 were evaluable for dose-limiting
toxicities and 28 were evaluable for efficacy. The median age was
27 (range 12-76) and 21 patients (68%) were ≤39 years old. Patients
received a median of 3 (range 1-9) prior therapies, including 10
patients (32%) who had previous treatment with gemcitabine.
- The 18-week event-free survival rate (EFS; time from treatment
initiation until disease progression or death due to any cause) was
39% (11/28) across all dose levels. The EFS observed in the
study compares favorably to historical cohorts with a similar
patient population where a 16-week EFS of ~12% has been
reported1.
- The maximum tolerated dose (MTD) of azenosertib was determined
to be 150 mg daily on a 5:2 schedule (5 days on, 2 days off) +
gemcitabine 800 mg/m2.
- At the MTD, the most frequent grade ≥3 adverse events (≥20%)
included thrombocytopenia and lymphopenia (33% each); there were no
grade 4 thrombocytopenia events or instances of febrile neutropenia
at the MTD.
- Data support further investigation of azenosertib administered
in combination with gemcitabine in patients with R/R osteosarcoma
in an upcoming investigator-initiated Phase 2 trial.
1 Lagmay JP, et al. J Clin Oncol. 2016;34(25):3031-3038.
“Historically, the management of relapsed and/or refractory
osteosarcoma has been limited to cytotoxic chemotherapy and only
recently, tyrosine kinase inhibitors, with suboptimal outcomes,”
said Viswatej Avutu, M.D., Sarcoma Medical Oncology Service and
Pediatric Sarcoma Team, Memorial Sloan Kettering Cancer Center, New
York, NY. “Azenosertib provides promise as a novel class of drugs
and offers hope for a well-tolerated and potentially efficacious
treatment option that is desperately needed.”
Study DesignPhase 1 dose-finding study
(NCT04833582) assessed azenosertib administered in combination with
gemcitabine in patients ≥12 years of age. The primary endpoint was
the incidence and severity of dose-limiting toxicities. Secondary
endpoints included the incidence and severity of adverse events and
EFS at 18 weeks per RECIST v1.1.
Poster Presentation Details:The full abstract
(#11525) is available here on the ASCO Congress
portal.Title: Phase 1 Results of the WEE1
Inhibitor, Azenosertib, in Combination With Gemcitabine in Adult
and Pediatric Patients With Relapsed or Refractory
Osteosarcoma.Presenter: Dr. Viswatej Avutu,
Sarcoma Medical Oncology Service and Pediatric Sarcoma Team,
Memorial Sloan Kettering Cancer Center, New York, NYSession
Title: Poster Session – SarcomaSession Date and
Time: June 1, 2024. 1:30-4:30 PM CDT
About AzenosertibAzenosertib is a novel,
selective, and orally bioavailable inhibitor of WEE1 currently
being evaluated as a monotherapy and combination clinical studies
in ovarian cancer and additional tumor types. WEE1 acts as a master
regulator of the G1-S and G2-M cell cycle checkpoints, through
negative regulation of both CDK1 and CDK2, to prevent replication
of cells with damaged DNA. By inhibiting WEE1, azenosertib enables
cell cycle progression, despite high levels of DNA damage, thereby
resulting in the accumulation of DNA damage and leading to mitotic
catastrophe and cancer cell death.
About Zentalis Pharmaceuticals
Zentalis® Pharmaceuticals, Inc. is a clinical-stage
biopharmaceutical company discovering and developing clinically
differentiated small molecule therapeutics targeting fundamental
biological pathways of cancers. The Company’s lead product
candidate, azenosertib (ZN-c3), is a potentially first-in-class and
best-in-class WEE1 inhibitor for advanced solid tumors and
hematologic malignancies. Azenosertib is being evaluated as a
monotherapy and in combination across multiple clinical trials and
has broad franchise potential. In clinical trials, azenosertib has
been well tolerated and has demonstrated anti-tumor activity as a
single agent across multiple tumor types and in combination with
several chemotherapy backbones. As part of its azenosertib clinical
development program, the Company is exploring enrichment strategies
targeting tumors of high genomic instability, such as Cyclin E1
positive tumors, homologous recombination deficient tumors and
tumors with oncogenic driver mutations. The Company is also
leveraging its extensive experience and capabilities across cancer
biology and medicinal chemistry to advance its research on protein
degraders. Zentalis has operations in both New York and San
Diego.
For more information, please visit www.zentalis.com. Follow
Zentalis on X/Twitter at @ZentalisP and on LinkedIn
at www.linkedin.com/company/zentalis-pharmaceuticals.
ZENTALIS® and its associated logo are trademarks of Zentalis
and/or its affiliates. All website addresses and other links in
this press release are for information only and are not intended to
be an active link or to incorporate any website or other
information into this press release.
Forward-Looking StatementsThis press release
contains forward-looking statements within the meaning of the U.S.
Private Securities Litigation Reform Act of 1995. All statements
contained in this press release that do not relate to matters of
historical fact should be considered forward-looking statements,
including statements regarding our plans to present final results
from a Phase 1 trial of azenosertib and gemcitabine in
relapsed/refractory osteosarcoma at the 2024 American Society of
Clinical Oncology Annual Meeting in Chicago; plans for an
investigator-initiated Phase 2 trial evaluating azenosertib
combined with gemcitabine in R/R osteosarcoma; our plans to present
additional data on azenosertib in gynecological malignancies later
in 2024; the potential for azenosertib to be first-in-class and
best-in-class; the broad franchise potential of azenosertib; our
plans with respect to the development of our product candidates,
including azenosertib; and the potential benefits of azenosertib,
including the potential benefits of the design thereof, the value
potential of the asset, and the potential to improve outcomes for
patients. The terms “continue,” “expect,” “look forward,” “on
track,” “potential,” “promise,” “upcoming,” “will,” and similar
references are intended to identify forward-looking statements,
although not all forward-looking statements contain these
identifying words. These statements are neither promises nor
guarantees, but involve known and unknown risks, uncertainties and
other important factors that may cause our actual results,
performance or achievements to be materially different from any
future results, performance or achievements expressed or implied by
the forward-looking statements, including, but not limited to, the
following: our limited operating history, which may make it
difficult to evaluate our current business and predict our future
success and viability; we have and expect to continue to incur
significant losses; our need for additional funding, which may not
be available; our plans, including the costs thereof, of
development of any diagnostic tools; our substantial dependence on
the success of our lead product candidates; the outcome of
preclinical testing and early trials may not be predictive of the
success of later clinical trials; failure to identify additional
product candidates and develop or commercialize marketable
products; potential unforeseen events during clinical trials could
cause delays or other adverse consequences; risks relating to the
regulatory approval process or ongoing regulatory obligations;
failure to obtain U.S. or international marketing approval; our
product candidates may cause serious adverse side effects;
inability to maintain our collaborations, or the failure of these
collaborations; our reliance on third parties; effects of
significant competition; the possibility of system failures or
security breaches; risks relating to intellectual property; our
ability to attract, retain and motivate qualified personnel, and
risks relating to management transitions; significant costs as a
result of operating as a public company; and the other important
factors discussed under the caption “Risk Factors” in our most
recently filed periodic report on Form 10-K or 10-Q and subsequent
filings with the U.S. Securities and Exchange Commission (SEC) and
our other filings with the SEC. Any such forward-looking statements
represent management’s estimates as of the date of this press
release. While we may elect to update such forward-looking
statements at some point in the future, we disclaim any obligation
to do so, even if subsequent events cause our views to change.
Contact:Elizabeth Pingpank
Hickinehickin@zentalis.com860.463.0469
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