ROCKVILLE, Md. and SUZHOU, China, Oct. 7, 2024
/PRNewswire/ -- Ascentage Pharma (6855.HK), a global
biopharmaceutical company engaged in discovering, developing and
commercializing therapies to address global unmet medical needs
primarily for malignancies, today announced that APG-2449, a
FAK/ALK/ROS1 tyrosine kinase inhibitor (TKI), has been cleared by
the Center for Drug Evaluation (CDE) of China's National Medical Product
Administration (NMPA) to enter two registrational Phase III studies
that will separately evaluate APG-2449 in patients with non-small
cell lung cancer (NSCLC) who are resistant to or intolerant of
second-generation anaplastic lymphoma kinase (ALK) TKIs; and
treatment-naïve patients with ALK-positive advanced or locally
advanced NSCLC.
These two pivotal studies will be multicenter, open-label,
randomized, registrational Phase III studies: first one is to
evaluate the efficacy and safety of APG-2449 versus platinum-based
chemotherapies in patients with NSCLC who are resistant to or
intolerant of second-generation ALK TKIs. The second registrational
Phase III study is designed to evaluate the efficacy and safety of
APG-2449 versus crizotinib as frontline therapies for
treatment-naïve patients with ALK-positive advanced or locally
advanced NSCLC. These two studies are the studies of an
investigational drug not yet approved by the FDA in the US.
ALK-positive NSCLC is a type of lung cancer with a specific
molecular profile characterized by the abnormal arrangement or the
fusion of the ALK gene which occurs in approximately 3%-5% of all
lung cancer cases. Most patients with ALK-positive NSCLC are
relatively young, non-smoking or only have a light smoking history,
and have a higher risk of brain metastasis.
Despite that multiple ALK-targeted therapies have already been
approved, more than half of patients with NSCLC treated with
second-generation ALK TKIs would develop acquired resistance, thus
the Chinese Society of Clinical Oncology (CSCO) guidelines'
recommendation of platinum-based chemotherapies as a treatment
option for patients who had failed on second-generation
ALK-targeted therapies. It is widely acknowledged that
chemotherapies are commonly associated with strong side effects and
there is a growing general preference for chemotherapy-free
regimens for the treatment of advanced tumors. Therefore, patients
with resistance to second-generation ALK TKIs have an enormous
unmet clinical need for new therapies that are effective and
safe.
APG-2449, developed by Ascentage Pharma, is an orally-active
small molecule FAK inhibitor and a third-generation ALK/ROS1 TKI,
and the first FAK inhibitor cleared by the CDE to enter clinical
study in China. In the
first-in-human trial, APG-2449 demonstrated preliminary clinical
benefit and favorable tolerability in patients with NSCLC who were
either second-generation ALK TKI resistant or treatment-naïve.
APG-2449 also showed potential inhibitory effect on brain
metastases, with its ability to cross the blood-brain barrier
confirmed through pharmacokinetics (PK) analysis on cerebrospinal
fluid. Biomarker analysis found that the phosphorylated FAK (pFAK)
expression in tumor tissues at baseline in patients with NSCLC who
were second-generation ALK TKI-resistant, were positively
correlated with the progress-free survival (PFS) after treatment
with APG-2449, indicating that elevated phosphorylated FAK could be
associated with drug resistance to second-generation ALK TKIs.
Prof. Li Zhang, the principal
investigator of these two registrational Phase III studies from
Sun Yat-sen University Cancer
Center, commented, "APG-2449 is an effective multitargeted
inhibitor that acts on FAK/ALK/ROS1. In previously released
clinical data, APG-2449 consistently showed manageable safety and
favorable antitumor activity in patients with NSCLC. We are
particularly encouraged by the preliminary efficacy observed in
patients with resistance to second-generation ALK TKIs, as it
suggests that multitargeted inhibition on FAK and ALK may offer a
new strategy for the management of patients with NSCLC resistant to
second-generation ALK TKIs. We look forward to initiating the two
registrational Phase III studies of APG-2449 in order to further
validate the drug candidate and allow more patients to benefit from
this novel therapeutic agent as soon as possible."
"There is considerable unmet clinical need in the field of
NSCLC. APG-2449, a FAK/ALK/ROS1 TKI, has already showed its
therapeutic potential in the released clinical data," said Dr.
Yifan Zhai, Chief Medical Officer of
Ascentage Pharma. "The CDE's approvals for the two registrational
Phase III studies of APG-2449 are very encouraging as they mark a
major milestone in the drug candidate's clinical development. To
fulfill our mission of addressing unmet clinical needs in
China and around the world, we
will expeditiously advance these clinical development programs for
the benefit of more patients."
References:
- https://ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.9071
- https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3124
About Ascentage Pharma
Ascentage Pharma (6855.HK) is a global, integrated
biopharmaceutical company engaged in discovering, developing and
commercializing therapies to address global unmet medical needs
primarily in malignancies. On October 28,
2019, Ascentage Pharma was listed on the Main Board of the
Stock Exchange of Hong Kong Limited with the stock code
6855.HK.
The company has built a rich pipeline of innovative drug
candidates that includes novel, highly potent Bcl-2 and dual
Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and
MDM2-p53 pathways, and next-generation TKIs. Ascentage Pharma is
also the only company in the world with active clinical programs
targeting all three known classes of key apoptosis regulators. The
company has conducted more than 40 clinical trials in the US,
Australia, Europe, and China, including 11 registrational studies
(completed/ ongoing/planned).
Olverembatinib, the company's first lead asset developed for the
treatment of drug-resistant chronic myeloid leukemia (CML) and the
company's first approved product in China, has been granted Priority Review
Designations and Breakthrough Therapy Designations by the Center
for Drug Evaluation (CDE) of China National Medical Products
Administration (NMPA). To date, the drug had been included into the
China National Reimbursement Drug List (NRDL). Furthermore,
olverembatinib has been granted Orphan Drug Designations (ODDs) and
a Fast Track Designation (FTD) by the US FDA, and an Orphan
Designation by the EMA of the EU.
To date, Ascentage Pharma has obtained a total of 16 ODDs from
the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of
the company's investigational drug candidates. Leveraging its
robust R&D capabilities, Ascentage Pharma has built a portfolio
of global intellectual property rights and entered into global
partnerships and other relationships with numerous leading
biotechnology and pharmaceutical companies such as Takeda,
AstraZeneca, Merck, Pfizer and Innovent; and research and
development relationships with leading research institutions such
as Dana-Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer
Center, National Cancer Institute and the University of Michigan.
The company has built a talented team with a wealth of global
experience in the discovery and development of innovative drugs and
fully functional commercial manufacturing and Sales & Marketing
teams. One pivotal aim of Ascentage Pharma is to continuously
strengthen its R&D capabilities and accelerate its clinical
development programs, in order to fulfil its mission of addressing
unmet clinical needs in China and
around the world for the benefit of more patients.
Forward-Looking Statements
The forward-looking statements made in this article relate only
to the events or information as of the date on which the statements
are made in this article. Except as required by law, Ascentage
Pharma undertakes no obligation to update or revise publicly any
forward-looking statements, whether as a result of new information,
future events, or otherwise, after the date on which the statements
are made or to reflect the occurrence of unanticipated events. You
should read this article completely and with the understanding that
our actual future results or performance may be materially
different from what we expect. In this article, statements of, or
references to, our intentions and expectations or those of any of
our Directors or our Company are made as of the date of this
article. Any of these intentions and expectations may alter in
light of future development.
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