Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM)
and AstraZeneca PLC (“AstraZeneca”) will present data from the
ongoing Phase II clinical trial of savolitinib in patients with
papillary renal cell carcinoma (“PRCC”) at the 2017 Genitourinary
Cancers Symposium sponsored by the American Society of Clinical
Oncology (“ASCO-GU”), to be held in Orlando, Florida from February
16 to 18, 2017. Savolitinib, a highly selective inhibitor of c-Met
receptor tyrosine kinase, has shown early clinical benefit in
multiple Phase I and II studies in a number of cancers. It was
developed as a potent and highly selective oral inhibitor
specifically designed to address issues observed in the clinic with
first-generation c-Met inhibitors, including renal toxicity.
PRCC, the second most common histologic subtype of renal cell
carcinoma (“RCC”), is associated with alterations in the c-Met gene
(e.g. mutations, amplifications, and/or chromosomal changes).
Therapies that are currently available for RCC patients have
demonstrated only modest benefit in PRCC and there are no therapies
specifically approved for the treatment of c-Met-driven PRCC.
National Comprehensive Cancer Network guidelines recommend
enrolling patients in clinical trials for first-line systemic
therapy.
“There is a clear unmet medical need in PRCC,” said Toni
Choueiri, Director of the Lank Center for Genitourinary Oncology,
Dana-Farber Cancer Institute. “The dataset from this Phase II study
is compelling, with a very clear efficacy signal in MET-driven
patients and an encouraging long duration of response, while
remaining very well tolerated.” He added, “These results support
the initiation of the pivotal Phase III trial in a selected
population of MET-driven PRCC. This innovative patient selection
approach would be the first ever molecularly selected trial in
renal cell carcinoma.”
“We are delighted to report this highly encouraging
progression-free survival data in Met-driven papillary renal cell
carcinoma, a disease with no approved treatment options,” said
Christian Hogg, Chief Executive Officer of Chi-Med. “With
development of the companion diagnostic assay to screen Met-driven
disease now also complete we are preparing for the initiation of
our global Phase III study, the first global registration trial for
savolitinib.”
The current Phase II trial is the largest prospective clinical
study ever conducted in PRCC patients. It is a global single arm
study of savolitinib in 109 patients with locally advanced or
metastatic PRCC and was initiated in May 2014. It is being
conducted in 22 clinical centers in the US, Canada, UK, and Spain,
and completed enrollment in October 2015. Additional details about
this study may be found at clinicaltrials.gov, using identifier
NCT02127710. The most recent results of the study will be presented
in detail as follows:
Presentation Title: A Single-Arm Biomarker-Based
Phase II Trial of Savolitinib in Patients with Advanced Papillary
Renal Cell Cancer
Authors: Toni K. Choueiri, Elizabeth
Plimack, Hendrik-Tobias Arkenau, Eric Jonasch, Daniel Y. C. Heng,
Thomas Powles, Melanie M. Frigault, Edwin Clark, Amir Handzel,
Humphrey Gardner, Shethah Morgan, Laurence Albiges, Sumanta Kumar
Pal
Abstract No: 436
Session: Session C: Penile,
Urethral, and Testicular Cancers; Renal Cell Cancer
Date &
Time: Saturday, February 18, 2017, 7:00 AM-7:55 AM and 11:30
AM-1:00 PM (EST)
Once presented, the presentation will be available at
www.chi-med.com/news. Further information about ASCO-GU is
available at gucasym.org.
Chi-Med and AstraZeneca are currently initiating a global
pivotal Phase III trial, the first pivotal study ever conducted in
c-Met-driven PRCC and the first molecularly selected trial in
RCC.
Over the course of 2017, Chi-Med and AstraZeneca are also
conducting a comprehensive molecular epidemiology study of
approximately 300 PRCC patient samples to further understand the
correlations between c-Met alterations and patient outcomes,
including any predictive biomarkers.
ABSTRACT
A single-arm biomarker-based phase II trial of savolitinib in
patients with advanced papillary renal cell cancer (PRCC)
Toni K. Choueiri1, Elizabeth Plimack2, Hendrik-Tobias Arkenau3,
Eric Jonasch4, Daniel Y. C. Heng5, Thomas Powles6, Melanie M.
Frigault7, Edwin Clark7, Amir Handzel7, Humphrey Gardner7, Shethah
Morgan8, Laurence Albiges9, Sumanta Kumar Pal10
1Dana-Farber Cancer Institute, Boston, US 2Fox Chase Cancer
Center, Philadelphia, US 3Sarah Cannon Research Institute, London,
UK 4MD Anderson Cancer Centre, Houston, US 5Tom Baker Cancer
Center, Calgary, Canada 6Barts Cancer Institute, London, UK
7AstraZeneca, Waltham, US, 8AstraZeneca, Cambridge, UK 9Institute
Gustave Roussy, Paris, France 10City of Hope, Duarte, US
Background: Savolitinib (HMPL-504/Volitinib, AZD6094) is
a potent, selective mesenchymal epithelial transition (“MET”)
inhibitor (IC50 of 4 nM). MET and its ligand, hepatocyte
growth factor (“HGF”), are known to play an important role in the
molecular events underlying oncogenesis in PRCC, a disease without
a clear standard of care and marked by alterations of chromosome 7
(containing both MET and HGF genes) in a majority of patients as
well as gene amplification or MET kinase domain mutations (Albiges
et al 2014, Linehan et al, 2015).
Methods: This study evaluates savolitinib in PRCC
patients dosed at 600 mg daily until disease progression.
Objective Response Rate (“ORR”) is the primary endpoint.
Progression-Free Survival (“PFS”) & Duration of Response are
secondary endpoints. Patient Reported Outcome (“PRO”) and
Health-Related Quality of Life (“HRQoL”) questionnaires are
exploratory endpoints. Eligibility includes naïve and previously
treated metastatic PRCC, ECOG PS 0 or 1. Archival tumor was used to
centrally confirm PRCC pathology post hoc and to determine MET
status using Next Generation Sequencing (Foundation Medicine
Inc, US).
Results: As of 27 June 2016, 109 patients were dosed.
Best response was PR n=8, SD n=43, PD n=48 & 10 patients were
not evaluable for response. 44 patients are MET-driven (MET/HGF
gene copy number gain or kinase domain mutations), 46 patients were
MET-negative, 19 patients are status unknown. MET-driven pts
included Papillary Type I & II histologies. All 8 responders
were in the MET-driven group, 18% ORR in this subset. Median PFS in
the MET-driven group was 6.2 months (95% CI: 4.1–7.0) vs. 1.4
months (95% CI: 1.4–2.7) in the MET-negative group (p=0.002).
Overall 10/109 patients had adverse events (“AEs”) leading to
discontinuation. 23/109 patients had ≥ Grade 3 toxicity related to
savolitinib. The most common AEs (all grades) includes: nausea
(39%), fatigue (27%), edema (18%) and abnormal liver function tests
(LFTs) (17%). One death from hepatic encephalopathy was considered
related to savolitinib. PRO & HRQoL data was not statistically
analyzed, descriptive data support main efficacy findings.
Conclusions: In the largest biomarker-profiled trial
dedicated to PRCC, savolitinib was generally well tolerated with
anti-tumor activity in MET-driven patients. These findings warrant
further clinical investigation of savolitinib in MET-driven
PRCC.
About the Unmet Medical Need in c-Met-Driven PRCC
Patients
Worldwide, about 366,000 new patients are diagnosed with kidney
cancer annually, and the total market for kidney cancer treatments
is expected to reach US$4.5 billion in 2020, according to Frost
& Sullivan. RCC accounts for approximately 80-85% of kidney
cancer and has several histological sub-types with different
genetic and biochemical characteristics. Among these histologic
variants of RCC, clear cell RCC (“ccRCC”) is the most common,
accounting for 75-80% of RCC.
PRCC is the most common of the non-clear cell renal carcinomas
accounting for 10-15% of RCC. The proportion of PRCC patients whose
tumors are c-Met-driven has historically been estimated at 40-70%.
In the largest study to date, presented at the annual meeting of
the American Association for Cancer Research 2014, analysis of 220
frozen tumor samples catalogued in the French RCC Network indicated
that 55-60% of PRCC patients showed gains in Chromosome 7 (i.e.
c-Met amplification).
The biology and molecular characteristics of PRCC are different
from those of ccRCC. This results in significantly worse prognosis
and treatment outcomes for patients with PRCC when compared to
patients with ccRCC. Highlighting the unmet need is the fact that,
although there are several drugs approved for use in RCC (the
latest being approved in April 2016), these approvals were
generally on the basis of studies conducted with a preponderance of
ccRCC patients. The need for different agents and more specific
data tailored to the PRCC disease setting has been identified as a
critical gap in the care of these patients.
About Chi-Med
Chi-Med is an innovative biopharmaceutical company which
researches, develops, manufactures and sells pharmaceuticals and
healthcare-related consumer 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.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a
quickly growing portfolio of new medicines that has the potential
to transform patients’ lives and the Company’s future. With at
least six new medicines to be launched between 2014 and 2020 and a
broad pipeline of small molecules and biologics in development, we
are committed to advance New Oncology as one of AstraZeneca’s six
Growth Platforms focused on lung, ovarian, breast and blood
cancers. In addition to our core capabilities, we actively pursue
innovative partnerships and investments that accelerate the
delivery of our strategy, as illustrated by our investment in
Acerta Pharma in hematology.
By harnessing the power of four scientific platforms –
Immuno-Oncology, the genetic drivers of cancer and resistance, DNA
Damage Response and Antibody Drug Conjugates – and by championing
the development of personalized combinations, AstraZeneca has the
vision to redefine cancer treatment and one day eliminate cancer as
a cause of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in
three main therapy areas – Oncology, Cardiovascular & Metabolic
Diseases and Respiratory. The Company also is selectively active in
the areas of autoimmunity, neuroscience and infection. AstraZeneca
operates in over 100 countries and its innovative medicines are
used by millions of patients worldwide. For more information,
please visit www.astrazeneca.com and follow us on Twitter
@AstraZeneca.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the "safe harbor" provisions of the US 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
savolitinib, plans to initiate clinical studies for savolitinib in
PRCC, 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
candidate savolitinib 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 savolitinib 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
US 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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version on businesswire.com: http://www.businesswire.com/news/home/20170214005672/en/
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LimitedRichard Gray / Andrew Potts+44 (20) 7886 2500
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