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
Zai Lab (NASDAQ: ZLAB) announced groundbreaking research published in Cell, offering new insights into HRD-positive ovarian cancer treatment. The study, supported by Zai Lab, revealed that niraparib, a PARP inhibitor, achieves high response rates and reshapes the tumor microenvironment (TME) in HRD-positive ovarian cancer patients. Key findings include:
1. Niraparib monotherapy achieved 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively.
2. The study identified eTregs as key responders to HRD and neoadjuvant therapies.
3. Combining niraparib with Zai Lab's investigational CCR8 antibody, ZL-1218, showed enhanced tumor suppression in pre-clinical models.
This research opens new avenues for immunotherapy and combination treatments in HRD-positive ovarian cancer and other HRD-related cancers.
- Niraparib monotherapy achieved high response rates of 62.5% (RECIST v.1.1) and 73.6% (GCIG CA125) in HRD-positive ovarian cancer patients
- Combination of niraparib and ZL-1218 (CCR8 antibody) showed enhanced tumor suppression in pre-clinical models
- Study provides new targets for immunotherapy and combination regimens in HRD-positive ovarian cancer
- Hematologic toxicities were the most common treatment-related adverse events with niraparib monotherapy
Insights
The publication from Zai Lab presents compelling data on the combination of niraparib and ZL-1218 for treating HRD-positive ovarian cancer. The study underscores the importance of the tumor microenvironment (TME) and its role in therapeutic efficacy. Notably, the high response rates of 62.5% and 73.6% for niraparib monotherapy in HRD tumors are remarkable, suggesting significant clinical benefits. Furthermore, the identification of key immune cell populations such as eTregs and their modulation by the CCR8 antibody, ZL-1218, presents new avenues for targeted immunotherapy. This approach could potentially enhance the sensitivity of PARP inhibitors, aligning with the broader shift towards personalized oncology treatments. In the short term, these findings could result in expanded clinical trials and increased investment in HRD-targeted therapies. Long-term, they could transform the standard of care for HRD-positive ovarian cancer, reducing tumor burden more effectively than current treatments.
However, the study's pre-clinical nature and the need for further trials to confirm these benefits in a clinical setting should be noted. Investors should keep an eye on upcoming clinical data for a more definitive assessment of the combination therapy's potential.
The publication of this study in Cell is noteworthy, as it demonstrates significant progress in the oncology field. For Zai Lab (NASDAQ: ZLAB; HKEX: 9688), these findings could catalyze greater market interest and potentially drive up stock prices. The focus on niraparib and ZL-1218 could open up substantial new revenue streams, particularly given the high prevalence of HRD-positive ovarian cancer. The high response rates and manageable safety profile reported are promising indicators for potential market adoption.
From a market perspective, this research could strengthen Zai Lab's position in the competitive oncology market, possibly leading to strategic partnerships or acquisitions aimed at expanding their pipeline. It's important, however, to consider that such breakthroughs often face regulatory hurdles and the uncertainty of clinical trial outcomes. Investors should be cautious yet optimistic, as the long-term implications for market share and revenue growth are significant but contingent on successful clinical validation.
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
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% and73.6% 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
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
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FAQ
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