SUZHOU, China, and ROCKVILLE, Md., June 1, 2024
/PRNewswire/ -- Ascentage Pharma (6855.HK), a global
biopharmaceutical company engaged in developing novel therapies for
cancer, chronic hepatitis B (CHB), and age-related diseases,
announced today that it has released updated data of its novel drug
candidate AGP-2449, a FAK/ALK/ROS1 tyrosine kinase inhibitor (TKI),
in patients with non-small-cell lung cancer (NSCLC) in a poster
presentation at the 60th American Society of Clinical Oncology
(ASCO) Annual Meeting taking place in Chicago, IL. This is the third consecutive
year in which clinical data from this study of APG-2449 were
selected for presentations at the ASCO Annual Meeting.
The ASCO Annual Meeting showcases the most cutting-edge research
in clinical oncology and state-of-the-art advanced cancer therapies
and is the world's most influential and prominent scientific
gathering of the clinical oncology community. Presenting clinical
development progress at the ASCO Annual Meeting for the seventh
consecutive year, Ascentage had four clinical studies of three of
the company's proprietary drug candidates selected for
presentations, including an oral report, at ASCO 2024.
Results presented this year reaffirmed the therapeutic potential
of APG-2449 in NSCLC, with data demonstrating preliminary efficacy
in patients with NSCLC who were TKI naïve and resistant to
second-generation ALK TKIs, as well as early antitumor activity in
brain metastases. Biomarker analysis showed that, in patients with
NSCLC resistant to second-generation ALK TKIs, phosphorylated FAK
(pFAK) expression levels in tumor tissue at baseline and reduction
in pFAK levels in peripheral blood mononuclear cells (PBMCs) were
correlated with responses to APG-2449.
"APG-2449 is an effective multitargeted inhibitor that acts on
FAK/ALK/ROS1. Compared to the data released at last year's ASCO
Annual Meeting, the latest results presented this year continued to
show manageable safety and favorable antitumor activity in patients
with NSCLC," said Prof. Li Zhang,
the principal investigator of this study from Sun Yat-sen University Cancer Center. "We are
very 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 hope that Ascentage Pharma will
conduct further studies on APG-2449 and allow more patients to
benefit from this novel therapeutic agent as soon as possible."
"These data of APG-2449 in patients with NSCLC revealed a
connection between resistance to ALK inhibitors and the FAK
pathway, thus suggesting that the multitargeted FAK/ALK/ROS1 TKI
APG-2449 may bring renewed hope to patients with NSCLC who are
resistant to second-generation ALK inhibitors. This finding is
indeed very encouraging," said Dr. Yifan
Zhai, Chief Medical Officer of Ascentage Pharma. "Remaining
committed to the mission of addressing unmet clinical needs in
China and around the world, we
will press forward with this clinical development program in order
to bring a safe and effective new treatment option to patients in
need."
Highlights of these data presented at ASCO 2024 are as
follows:
Updated study results of novel FAK/ALK/ROS1 inhibitor
APG-2449 in patients (pts) with non-small-cell lung cancer (NSCLC)
resistant to second-generation ALK inhibitors.
Abstract#: 3124
Session Title: Developmental Therapeutics—Molecularly
Targeted Agents and Tumor Biology
Date and Time: June 1, 2024, Saturday, 9:00 AM – 12:00 PM
(Central Time)
First Author: Yuxiang Ma, MD, PhD, Sun Yat-sen University Cancer Center,
Guangzhou, Guangdong, China.
Highlights:
Background: ALK inhibitors increase FAK pathway gene expression
in ALK+ NSCLC cell lines, with the highest induced
expression in drug-tolerant persister cells. This suggests that FAK
pathway activation is involved in the mechanism that leads to ALK
TKI resistance in ALK+ NSCLC. APG-2449 is an orally
active FAK inhibitor and a third-generation ALK/ROS1 TKI that has
shown potent antitumor activity in preclinical models. This poster
reports further safety and efficacy data of APG-2449.
Patient enrollment and methods:
- This study comprises dose-escalation and dose-expansion
portions. 1,200 mg daily (QD) was determined as the RP2D. There
were two cohorts in the dose-expansion portion: Cohort 1 included
patients with NSCLC who were resistant to second-generation ALK
TKIs; Cohort 2 included patients with NSCLC who were ALK or ROS1
TKI naïve.
- As of April 2, 2024, a total of
144 patients with NSCLC, mesothelioma, or ovarian cancer were
treated with APG-2449 at doses ranging from 150 – 1,500 mg. The
median (range) age of patients was 53 (21-78) years, and 53.5% were
female.
Efficacy results:
- The ORRs of APG-2449 in patients with ROS1+ and ALK+ TKI-naïve
NSCLC (n=36) were 68.2% (15/22) and 78.6% (11/14), respectively. Of
the 22 patients with NSCLC resistant to second-generation ALK
inhibitors and without targetable bypass gene mutations (e.g.,
KRAS G12C, BRAF V600E), 10 achieved PRs (10/22; 45.5%).
Among the patients treated at RP2D, 12 had brain metastasis at
baseline, 9 of whom achieved intracranial PR, resulting in an
intracranial ORR of 75.0%.
- Biomarker analysis found that, in patients with NSCLC that was
resistant to second-generation ALK TKIs, responses to APG-2449 were
correlated with pFAK levels in tumor tissues at baseline and
reductions in pFAK levels in PBMCs.
Safety results: A total of 129 (89.6%) patients had
treatment‑related adverse events (TRAEs), the most frequent (≥10%)
of which were elevated serum creatinine (49.3%), increase in
alanine aminotransferase (42.4%), increase in aspartate
aminotransferase (36.1%); nausea (28.5%); vomiting (23.6%);
diarrhea (22.9%); decreased leukocyte count (22.2%), decreased
neutrophil count (17.4%) and rash (13.2%). In all, 20 (13.9%) TRAEs
were grade ≥ 3.
Conclusions: APG-2449 demonstrated preliminary efficacy in
patients with NSCLC whose disease was TKI naïve and resistant to
second-generation ALK inhibitors, especially in brain metastases.
Biomarker analysis showed that, in patients with NSCLC resistant to
second-generation ALK TKIs, responses to APG-2449 PFS were
correlated with pFAK levels in tumor tissues at baseline and
reductions in pFAK levels in PBMCs.
*APG-2449 is an investigational drug that has not been
approved in any country and region.
Appendix: The four clinical studies of Ascentage Pharma's three
drug candidates, including lisaftoclax, presented at this year's
ASCO Annual Meeting.
Drug
Candidates
|
Abstract
Title
|
Abstract
#
|
Format
|
Olverembatinib
(HQP1351)
|
Updated efficacy
results of
olverembatinib (HQP1351) in patients
withtyrosinekinase inhibitor (TKI)-
resistantsuccinatedehydrogenas
e (SDH)-deficientgastrointestinal
stromal tumor (GIST)and
paraganglioma
|
#11502
|
Oral Report
|
Lisaftoclax
(APG-2575)
|
Safety and efficacy of
lisaftoclax, a
novel BCL-2 inhibitor, in combination
withazacitidine in patients with
treatment-naïve or relapsed
or refractory acute myeloid leukemia
|
#6541
|
Poster
Presentation
|
Updated efficacy and
safety results of
BCL-2 inhibitorlisaftoclax (APG-2575)
alone or combinedwithibrutinibor
rituximab in patients (pts)with
Waldenströmmacroglobulinemia
(WM)
|
#7078
|
Poster
Presentation
|
APG-2449
|
Updated study results
of novel
FAK/ALK/ROS1 inhibitor APG-2449 in
patients (pts) with non-small-cell lung
cancer (NSCLC) resistant tosecond-
generationALK inhibitors
|
#3124
|
Poster
Presentation
|
About Ascentage Pharma
Ascentage Pharma (6855.HK) is a
globally focused biopharmaceutical company engaged in developing
novel therapies for cancers, chronic hepatitis B, and age-related
diseases. 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.
Ascentage Pharma focuses on developing therapeutics that inhibit
protein-protein interactions to restore apoptosis, or programmed
cell death. The company has built a pipeline of 9 clinical drug
candidates, including 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 tyrosine kinase inhibitors
(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 is conducting more than 40 Phase
I/II clinical trials, including 5 global registrational phase III
studies, in the US, Australia,
Europe, and China. Ascentage Pharma has been designated
for multiple Major National R&D Projects, including five Major
New Drug Projects, one New Drug Incubator status, four Innovative
Drug Programs, and one Major Project for the Prevention and
Treatment of Infectious Diseases.
Olverembatinib, the company's core drug candidate 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 2022 National Reimbursement
Drug List (NRDL). Furthermore, olverembatinib has been granted an
Orphan Drug Designation (ODD) 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 with numerous renowned
biotechnology and pharmaceutical companies and research institutes
such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo
Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca. The
company has built a talented team with global experience in the
discovery and development of innovative drugs and is setting up its
world-class 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 or those of any of our Directors or our Company are made
as of the date of this article. Any of these intentions may alter
in light of future development.
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