Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM)
today announces that results from two non-small cell lung cancer
(“NSCLC”) clinical studies will be presented at WCLC in Vienna,
Austria, from December 4 to 7, 2016. Results from the positive
Phase II third-line NSCLC clinical trial of fruquintinib, a highly
selective and potent oral inhibitor of vascular endothelial growth
factor receptors (“VEGFR”), will be detailed in an oral
presentation. Results from the ongoing Phase Ib first-line NSCLC
clinical trial of epitinib, a highly selective inhibitor of the
epidermal growth factor receptor (“EGFR”) designed to optimize
brain penetration, will also be presented.
In September 2015, Chi-Med announced that the fruquintinib Phase
II NSCLC clinical trial had successfully achieved its primary
endpoint. The oral and poster presentations will include more
mature data than those included in the following fruquintinib and
epitinib study abstracts.
The results of the two studies will be presented in detail at
WCLC as follows:
Type: Oral Presentation Title: A
Randomized, Multi-Center, Double-Blind Phase II Study of
Fruquintinib in Patients with Advanced Non-Small Cell Lung Cancer
Presenter: Shun Lu
Abstract: #4571
Session:
OA11 – Angiogenesis in Advanced Lung Cancer, Oral Session
Date
& Time: Tuesday, December 6, 2016 (11:00 AM – 12:30 PM)
Type: Poster Presentations Title: A
Phase I Dose Expansion Study of Epitinib to Evaluate Efficacy and
Safety in EGFR Mutation Positive (EGFRm+) NSCLC Patients with Brain
Metastasis
Authors: Qing Zhou, et al.
Abstract: #4253
1st Session: JCES01 Joint IASLC–Chinese
Society for Clinical Oncology /
Chinese Alliance Against Lung Cancer
Session (ID 413)
Date & Time: Sunday, December 4, 2016 (10:30 AM – 11:30
AM)
2nd Session: 07. Advanced NSCLC
P2.03b – Poster Session with Presenters
Present (ID 465)
Date & Time: Tuesday, December 6, 2016 (2:30 PM – 3:45
PM)
The WCLC presentations will be made available for download at
www.chi-med.com/news on the following day.
Organized by the International Association for the Study of Lung
Cancer (IASLC) and held annually, WCLC is a global,
multidisciplinary scientific forum for sharing current knowledge
and research progress in lung cancer. For more information, please
visit: wclc2016.iaslc.com.
NOTES TO EDITORS
Full Abstracts
A Randomized, Multi-Center, Double-Blind
Phase II Study of Fruquintinib in Patients with Advanced Non-Small
Cell Lung Cancer
Shun Lu, Jianhua Chang, XiaoQing Liu, Jianhua Shi, You Lu, Wei
Li, Jinji Yang, Jianying Zhou, Jie Wang, Lei Yang, Zhiwei Chen,
Xiangdong Zhou, Zhe Liu, Ye Hua, Weiguo Su.
Background
Targeting the tumor microenvironment, such as tumor
angiogenesis, has led to the successful development and approval of
a number of targeted therapies thereby changing the standard of
care for many types of cancer. However, treatment options are
limited in third-line non-small cell lung cancer (“NSCLC”)
patients. Fruquintinib is a potent and highly selective oral kinase
inhibitor targeting vascular endothelial growth factor receptors
and is currently in late stage development for multiple cancers.
This Phase II study was designed to evaluate the efficacy and
safety of fruquintinib in third-line NSCLC patients
(NCT02590965).
Methods
A total of 91 patients were randomized to receive best
supportive care (“BSC”) plus fruquintinib or BSC plus placebo in a
2:1 ratio from 12 Chinese clinical centers. Fruquintinib initial
dose was 5 mg once daily and treatment was given in every 4-week
cycle (3 weeks treatment followed by 1 week off). The primary
objective was to compare progression free survival (“PFS”) between
the two treatment groups. Secondary efficacy parameters included
objective response rate (“ORR”), disease control rate (“DCR”),
overall survival (“OS”). Tumor response was assessed per RECIST
1.1.
Results
As of August 7, 2015, median PFS was 3.8 months for the
fruquintinib group comparing with 1.2 months for the placebo group
(hazard ratio=0.27, p<0.001). The ORR was 16.4% for the
fruquintinib group comparing with 0% for the placebo group
(p=0.02). The DCR of the fruquintinib group was significantly
higher than that of the placebo group with a difference of 53.8%
(36.3, 71.4; 95% CI, p<0.001). OS was not mature and initial
analysis revealed 3- and 6-month OS rates of 90.2% and 68.3% for
the fruquintinib group, and 73.3% and 58.2% for the placebo group,
respectively. Adverse event was reported in 68.9% and 60.0%
patients in fruquintinib and placebo group, respectively. The
incidence of serious adverse events was 3.3% in the fruquintinib
group and 6.7% in the placebo group.
Conclusion
Fruquintinib in third-line NSCLC met the primary efficacy
endpoint of PFS and demonstrated superiority in the secondary
endpoints of ORR and DCR as compared with placebo. OS has yet to
mature. Fruquintinib was generally well tolerated and safety
profile consistent with previously reported. These results support
further development of fruquintinib in third-line NSCLC patients. A
randomized, double-blind, multi-center Phase III registration study
was initiated in December 2015 (NCT02691299). Clinical trial
information: NCT02590965.
A Phase Ib study of Epitinib to evaluate
efficacy and safety in EGFR mutation positive (EGFRm+) NSCLC
patients with brain metastasis
Qing Zhou, Bin Gan, Qunying Hong, Mengzhao Wang, Xiaoqing Liu,
Yi-Long Wu.
Background
A significant portion of patients with NSCLC develop brain
metastasis. Patients with brain metastasis suffer from poor
prognosis with a median survival of less than 6 months and low
quality of life with limited treatment options. First generation
EGFR tyrosine kinase inhibitors (EGFR TKIs) have demonstrated
significant clinical benefit for patients with EGFR-mutant NSCLC.
However, their effect on brain metastasis is limited due to poor
drug penetration into the brain. Epitinib is an EGFR TKI designed
to improve brain penetration. A Phase I dose escalation study on
epitinib has been completed and the recommended Phase 2 dose (RP2D)
determined. This Phase I dose expansion study was designed to
evaluate the efficacy and safety of epitinib in EGFR-mutant NSCLC
patients with brain metastasis.
Methods
This is an ongoing open label, multi-center Phase I dose
expansion study. EGFR-mutant NSCLC patients with confirmed brain
metastasis, either prior EGFR TKI treated or EGFR TKI treatment
naïve, were enrolled to receive oral epitinib 160 mg once daily.
Patients with extra-cranial disease progression while on treatment
with an EGFR TKI were excluded. Tumor response was assessed per
RECIST 1.1.
Results
As of May 31, 2016, 27 patients (13 EGFR TKI pretreated, 14 EGFR
TKI treatment naïve) have been enrolled and treated with epitinib.
The most frequent adverse events (“AEs”) were skin rash (89%),
elevated ALT (41%)/AST (37%), hyper-pigmentation (41%) and diarrhea
(30%). The most frequent Grade 3/4 AEs were elevations in ALT
(19%), gamma-GGT (11%), AST (7%), and hyperbilirubinemia (7%) and
skin rash (n=1, 4%). There have been no Grade 5 AEs to date. Among
the 24 efficacy evaluable patients (11 TKI pretreated, 13 TKI
naïve), 7 (7/24, 29%) achieved a partial response (“PR”), including
1 unconfirmed PR. All PRs occurred in EGFR TKI treatment naïve
patients (7/13, 53.8%). Of the 24 evaluable patients, 8 (5 EGFR
treatment naïve, 3 EGFR TKI pretreated) had measurable brain
metastasis (lesion diameter>10 mm per RECIST 1.1) with 2 PRs
(both EGFR TKI treatment naïve patients, 2/5, 40%).
Conclusion
Epitinib 160mg once daily treatment in EGFR-mutant NSCLC
patients with brain metastasis demonstrated clinical activity both
extra- and intra-cranial. Epitinib was well tolerated. The data to
data appears encouraging and warrants further development of
epitinib.
About NSCLC and TKIs to address EGFR-driven NSCLC
At an advanced stage, tumors secrete large amounts of vascular
endothelial growth factors (“VEGF”), a protein ligand, to stimulate
formation of excessive vasculature (angiogenesis) around the tumor
in order to provide greater blood flow, oxygen, and nutrients to
the tumor. VEGF and VEGFR play a pivotal role in tumor-related
angiogenesis, and inhibition of the VEGF/VEGFR pathway. This
represents an important therapeutic strategy in blocking the
development of new blood vessels essential for tumors to grow and
invade.
Every year, it is estimated that approximately 1.7 million new
patients around the world are diagnosed with NSCLC, according to
Frost & Sullivan. Lung cancer is the leading cause of cancer
death among both men and women, accounting for about one-third of
all cancer deaths, and more than breast, prostate and colorectal
cancers combined. TKIs are used in many cancer therapies and act by
blocking the cell signaling pathways that drive the growth of tumor
cells. The very high prevalence of lung cancer in China as compared
to the rest of the world is thought to be linked in part to the
high incidence of cigarette smoking in the country. To date,
several anti-VEGF/VEGFR agents have shown clinical efficacy against
a number of tumor types. Given the scale and growth in the China
oncology market, the market for VEGF/VEGFR inhibitors in China is
expected to develop quickly in the next few years.
Patients who have the EGFRm+ form of NSCLC, which occurs in an
estimated 10-15% of NSCLC patients in Europe and 30-40% of NSCLC
patients in Asia, are particularly sensitive to treatment with
currently available EGFR-TKIs. However, tumors almost always
develop resistance to treatment leading to disease progression.
Brain metastasis has been identified in 10-30% EGFRm+ NSCLC
patients at initial diagnosis and is one of the most devastating
complications of lung cancer with poor life expectancy around 5-10
months. However, currently marketed EGFR-TKIs are unable to
penetrate the blood-brain barrier with sufficient concentrations to
provide clinical benefit in the brain, leaving the majority of
patients with brain metastasis without an effective targeted
therapy.
About Fruquintinib
Fruquintinib (HMPL-013) is a highly selective small molecule
drug candidate that has been shown to inhibit VEGFR 24 hours a day
via an oral dose, without known off-target toxicities. It is
currently under the joint development in China by Chi-Med and its
partner Eli Lilly and Company. Two late stage, pivotal Phase III
registration studies are ongoing in lung cancer and colorectal
cancer. In addition, fruquintinib is also in clinical development
for gastric cancer.
Lung: The FALUCA trial is a randomized, double-blind,
placebo-controlled, multi-center, Phase III registration study
targeted at treating patients with advanced non-squamous NSCLC, who
have failed two lines of systemic chemotherapy. Enrollment began in
December 2015. Patients are randomized at a 2:1 ratio to receive
either: 5mg of fruquintinib orally once per day, on a
three-weeks-on / one-week-off cycle, plus BSC; or placebo plus BSC.
The primary endpoint is OS, with secondary endpoints including PFS,
ORR, DCR and duration of response. Chi-Med plans to enroll
approximately 520 patients in about 45 centers across China.
Additional details about this study may be found at
clinicaltrials.gov, using identifier NCT02691299.
Colorectal: The FRESCO trial is a randomized,
double-blind, placebo-controlled, multicenter, Phase III pivotal
trial in patients with locally advanced or metastatic colorectal
cancer who have failed at least two prior systemic antineoplastic
therapies, including fluoropyrimidine, oxaliplatin and irinotecan.
Enrollment was completed in May 2016. 416 patients were randomized
at a 2:1 ratio to receive either: 5mg of fruquintinib orally once
per day, on a three-weeks-on / one-week-off cycle, plus BSC; or
placebo plus BSC. The primary endpoint is OS, with secondary
endpoints including PFS, objective response rate, disease control
rate and duration of response. Once a pre-specified number of OS
events (deaths) have occurred, data analysis will commence.
Additional details of the FRESCO study may be found at
clinicaltrials.gov, using identifier NCT02314819.
Gastric: Chi-Med completed a Phase Ib dose finding study
of fruquintinib in combination with paclitaxel, which established a
combination regimen that was well tolerated. Chi-Med continues to
enroll patients in this Phase Ib to expand the data-set. Additional
details about this study may be found at clinicaltrials.gov, using
identifier NCT02415023.
About Epitinib
EGFR inhibitors have revolutionized the treatment of NSCLC with
EGFR activating mutations. However, existing EGFR inhibitors cannot
penetrate the blood-brain barrier effectively, leaving the majority
of patients with brain metastasis without an effective therapy. In
contrast, epitinib (HMPL-813) is a potent and highly selective oral
EGFR inhibitor designed to optimize brain penetration and has
demonstrated brain penetration and efficacy in pre-clinical
studies. Should epitinib be able to provide clinical benefit to
NSCLC patients with brain metastasis, subject to regulatory
approval, it may be well positioned to address a major global unmet
medical need. Additional details about this study may be found at
clinicaltrials.gov, using identifier NCT02590952.
About Chi-Med
Chi-Med is an innovative biopharmaceutical company which
researches, develops, manufactures and sells pharmaceuticals and
healthcare products. Its Innovation Platform, Hutchison MediPharma
Limited, focuses on discovering and developing innovative
therapeutics in oncology and autoimmune diseases for the global
market. Its Commercial Platform manufactures, markets, and
distributes prescription drugs and consumer health products in
China.
Chi-Med is majority owned by the multinational conglomerate CK
Hutchison Holdings Limited (SEHK: 0001). For more information,
please visit: www.chi-med.com.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the "safe harbor" provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These forward-looking
statements reflect Chi-Med’s current expectations regarding future
events, including its expectations for the clinical development of
fruquintinib or epitinib, plans to initiate clinical studies for
fruquintinib or epitinib, its expectations as to whether such
studies would meet their primary or secondary endpoints, and its
expectations as to the timing of the completion and the release of
results from such studies. Forward-looking statements involve risks
and uncertainties. Such risks and uncertainties include, among
other things, assumptions regarding enrollment rates, timing and
availability of subjects meeting a study’s inclusion and exclusion
criteria, changes to clinical protocols or regulatory requirements,
unexpected adverse events or safety issues, the ability of drug
candidates fruquintinib or epitinib to meet the primary or
secondary endpoint of a study, to obtain regulatory approval in
different jurisdictions, to gain commercial acceptance after
obtaining regulatory approval, the potential market of fruquintinib
or epitinib for a targeted indication and the sufficiency of
funding. Existing and prospective investors are cautioned not to
place undue reliance on these forward-looking statements, which
speak only as of the date hereof. For further discussion of these
and other risks, see Chi-Med’s filings with the U.S. Securities and
Exchange Commission and on AIM. Chi-Med undertakes no obligation to
update or revise the information contained in this press release,
whether as a result of new information, future events or
circumstances or otherwise.
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