Zai Lab-Supported Study Published in Cell Provides New Insights with Potential to Improve Treatment of HRD-Positive Ovarian Cancers, Including Through Combination PARP Inhibitor and CCR8 Therapy
July 15 2024 - 1:53PM
Business Wire
Manuscript represents the first publication
from China’s gynecology oncology field to be published in Cell
Publication highlights first-time learnings
about the landscape of ovarian cancer microenvironment stratified
by HRD and how a PARP inhibitor perturbs it
Data suggest combination of niraparib and
ZL-1218, an investigational CCR8 antibody, may decrease tumor
burden, offering synergistic potential for improving efficacy in
treatment of HRD tumors
Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today announced that
data published in the journal Cell demonstrate that neoadjuvant
monotherapy with the poly (ADP-ribose) polymerase (PARP) inhibitor
niraparib results in a high response rate and reshapes the tumor
microenvironment (TME), providing new targets for immunotherapy and
combination regimens in patients with homologous recombination
deficiency (HRD) positive ovarian cancer. The study revealed
niraparib preferentially suppresses certain immune cells that
support the growth of HRD-positive ovarian tumors.
This Zai Lab-supported study also showed that targeted clearance
of infiltrating regulatory T cells (eTregs) using Zai Lab’s
investigational CCR8 antibody, ZL-1218, significantly sensitized
niraparib against HRD tumors, resulting in decreased tumor burden
in pre-clinical models.
“Given the prevalence of HRD in cancer and its role in rendering
tumors vulnerable to PARP inhibition, this study fills the
knowledge gap regarding the impact of HRD and related therapies on
the tumor microenvironment,” said Professor Qinglei Gao, Chief of
Gynecologic Oncology Department, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology. “By
decoding the tumor-reactive T cells in the HRD-positive TME that
are regulated by eTregs, these findings have profound implications
for future oncology research and therapeutic development for
HRD-positive ovarian cancer and other HRD-related cancers.”
To investigate the effects of HRD, neoadjuvant therapies, and
their interactions on the TME, investigators utilized tumor tissues
from a clinical study (NCT04507841) evaluating niraparib for the
neoadjuvant treatment of unresectable ovarian cancer. In parallel,
tissue samples from patients receiving neoadjuvant chemotherapy
(NACT) were also collected.
Profiling of these samples yielded valuable data delineating the
divergence in TME between HRD-positive vs. homologous
recombination-proficient (HRP) tumors, as well as their respective
phenotypic evolution following the introduction of neoadjuvant
therapies.
Key findings of the study included:
- Patients receiving neoadjuvant monotherapy with niraparib
achieved 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG
CA125, respectively.
- Overall, the safety profile of NANT was manageable, and no new
safety signal was observed, with hematologic toxicities as the most
common treatment-related adverse events.
- The results indicate that NANT is an effective neoadjuvant
treatment option for controlling disease progression in patients
with HRD-positive high-grade serous ovarian cancer (HGSOC).
- eTregs were identified as key responders to HRD and neoadjuvant
therapies, co-occurring with other tumor-reactive T cells,
particularly terminally exhausted CD8+ T cells.
- The addition of the CCR8 antibody, ZL-1218, to niraparib showed
a significantly pronounced inhibitory effect on eTregs in
pre-clinical models, suppressing tumor growth without observable
toxicities, underscoring the potential of eTreg-focused
therapeutics for HGSOC and other HRD-related tumors.
“Zai Lab is pleased to support this important translational
research which breaks new ground in our understanding of the tumor
microenvironment in HRD-positive ovarian cancer,” said Rafael G.
Amado, M.D., President, Head of Global Research and Development,
Zai Lab. “By identifying new immunotherapeutic targets in the TME,
these findings could bolster efforts to improve outcomes for
patients with HRD+ tumors.”
About Zai Lab
Zai Lab (NASDAQ: ZLAB; HKEX: 9688) is an innovative,
research-based, commercial-stage biopharmaceutical company based in
China and the United States. We are focused on discovering,
developing, and commercializing innovative products that address
medical conditions with significant unmet needs in the areas of
oncology, autoimmune disorders, infectious diseases and
neuroscience. Our goal is to leverage our competencies and
resources to positively impact human health in China and
worldwide.
For additional information about Zai Lab, please visit
www.zailaboratory.com or follow us at
www.twitter.com/ZaiLab_Global.
Zai Lab Forward-Looking Statements
This press release contains forward-looking statements relating
to our future expectations, plans, and prospects, including,
without limitation, statements regarding the possible benefits,
safety, and efficacy of niraparib and ZL-1218; the potential
treatment of certain ovarian cancers and other solid tumors; and
risks and uncertainties associated with drug development and
commercialization. These forward-looking statements may contain
words such as “aim,” “anticipate,” “believe,” “could,” “estimate,”
“expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,”
“potential,” “will,” “would,” and other similar expressions. Such
statements constitute forward-looking statements within the meaning
of the Private Securities Litigation Reform Act of 1995.
Forward-looking statements are not statements of historical fact or
guarantees or assurances of future performance. Forward-looking
statements are based on our expectations and assumptions as of the
date of this press release and are subject to inherent
uncertainties, risks, and changes in circumstances that may differ
materially from those contemplated by the forward-looking
statements. Actual results may differ materially from those
indicated by such forward-looking statements as a result of various
important factors, including but not limited to (1) our ability to
successfully commercialize and generate revenue from our approved
products, (2) our ability to obtain funding for our operations and
business initiatives, (3) the results of our clinical and
pre-clinical development of our product candidates, (4) the content
and timing of decisions made by the relevant regulatory authorities
regarding regulatory approvals of our product candidates, (5) risks
related to doing business in China, and (6) other factors
identified in our most recent annual and quarterly reports and in
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Commission (SEC). We anticipate that subsequent events and
developments will cause our expectations and assumptions to change,
and we undertake no obligation to update or revise any
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future events, or otherwise, except as may be required by law.
These forward-looking statements should not be relied upon as
representing our views as of any date subsequent to the date of
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