Data for savolitinib in combination with
Tagrisso or Iressa presented at World Conference on Lung
Cancer1,2
New data give insights into disease
progression and potential next-generation treatment strategies in
patients with EGFR-mutated NSCLC with MET-amplification
AstraZeneca and its partner Chi-Med today presented preliminary
safety and clinical activity of savolitinib when given in
combination with either Tagrisso (osimertinib) or Iressa
(gefitinib) in two Phase Ib trials conducted in patients with
epidermal growth factor receptor (EGFR) mutation-positive non-small
cell lung cancer (NSCLC) with MET-amplification who had progressed
following 1st-line treatment with an EGFR inhibitor.1,2 In both
trials, the addition of savolitinib (600mg, once daily), an
investigational selective inhibitor of c-MET (mesenchymal
epithelial transition factor) receptor tyrosine kinase, to
osimertinib (80mg, once daily) or gefitinib (250mg, once daily)
demonstrated preliminary anti-tumour activity. The data were shared
in two oral presentations at the International Association for the
Study of Lung Cancer 18th World Conference on Lung Cancer (WCLC) in
Yokohama, Japan, 15-18 October 2017.
Dr. Myung-Ju Ahn, Department of Haematology & Oncology,
Samsung Medical Centre, Seoul, South Korea, said: “Secondary
resistance mechanisms often emerge during treatment with
mutation-targeted medicines, leading to disease progression. The
data presented at WCLC demonstrate the potential of utilising
savolitinib in cMET-driven lung cancers to address resistance
challenges.”
Susan Galbraith, Head of Oncology, AstraZeneca Research and
Early Development, said: “We are committed to developing innovative
medicines to overcome the key drivers of cancer mechanisms of
resistance and are strategically focused on developing effective
combinations. The latest results for savolitinib in combination
with osimertinib and gefitinib support our approach in
collaboration with Chi-Med.”
Preliminary results for savolitinib in combination with
osimertinib1
Early data on safety and anti-tumour activity for savolitinib
(600mg, once daily) plus osimertinib (80mg, once daily) in the
Phase Ib TATTON trial in patients with EGFR mutation-positive
(EGFRm) advanced NSCLC with MET-amplification were presented. In 66
patients treated with savolitinib plus osimertinib, the most common
all-causality adverse events (AEs) of any grade were nausea (44%),
vomiting (35%), fatigue (30%), and decreased appetite (30%), and
were consistent with the known safety profiles of both
therapies.
Preliminary data showed partial response according to RECIST 1.1
criteria in 28% of patients previously treated with
third-generation T790M-directed EGFR tyrosine kinase inhibitors
(TKIs), including osimertinib (n=25). In patients who had
progressed after prior treatment with a first- or second-generation
EGFR inhibitor, 53% of T790M-negative patients (n=15) had a partial
response, while 57% of T790M-positive patients (n=7) had a partial
response.
Preliminary data for savolitinib in combination with
gefitinib2
Data from a Phase Ib trial assessing savolitinib (600mg, once
daily) plus gefitinib (250mg, once daily) in patients in China with
EGFRm advanced NSCLC with MET-amplification who progressed
following EGFR-TKI therapy were also reported. The most common AEs
independent of causality in 51 patients were vomiting (39%),
increased ALT (37%), increased AST (35%), nausea (35%), and rash
(35%), and were consistent with the known safety profiles of both
therapies.
Preliminary results showed that 31% of patients achieved a
partial response according to RECIST 1.1 criteria, of which 52% of
T790M-negative patients (n=23) and 9% of T790M-positive patients
(n=23) had a partial response.
Christian Hogg, Chief Executive Officer of Chi-Med, said:
“MET-amplification impacts a meaningful proportion of patients with
EGFRm NSCLC who experience disease progression following treatment
with a tyrosine kinase inhibitor in the first- or second-line
setting. Among patients with this difficult-to-treat resistance
mechanism, there is a clear unmet medical need.”3-6
- ENDS -
NOTES TO EDITORS
About savolitinib
Savolitinib (AZD6094/HMPL-504) is a potential first-in-class
selective inhibitor of c-MET (also known as mesenchymal epithelial
transition factor) receptor tyrosine kinase, an enzyme which has
been shown to function abnormally in many types of solid tumours.
It was developed as a potent and highly selective oral
inhibitor.
Savolitinib was discovered by Chi-Med and is being developed in
collaboration with AstraZeneca. Savolitinib is currently being
studied in multiple tumour types worldwide including kidney, lung,
and gastric cancers, both as a monotherapy or in combination with
other targeted and immunotherapy agents.
About Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible
EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR-T790M
resistance mutations, with clinical activity against central
nervous system (CNS) metastases. Osimertinib 40mg and 80mg
once-daily oral tablets have been approved in more than 50
countries, including the US, EU, Japan and China, for patients with
EGFR T790M mutation-positive advanced NSCLC. Osimertinib is also
being investigated in the adjuvant setting and in combination with
other treatments.
About NSCLC
Lung cancer is the leading cause of cancer death among both men
and women, accounting for about one-quarter of all cancer deaths,
more than breast, prostate and colorectal cancers combined.
Approximately 10-15% of patients in the US and Europe, and 30-40%
of patients in Asia have EGFRm NSCLC. These patients are
particularly sensitive to treatment with currently available
EGFR-TKIs, which block the cell signalling pathways that drive the
growth of tumour cells. However, tumours almost always develop
resistance to EGFR-TKI treatment, leading to disease progression.
Approximately half of patients develop resistance to approved
EGFR-TKIs such as gefitinib and erlotinib due to the resistance
mutation, EGFR T790M. Osimertinib also targets this secondary
mutation that leads to disease progression. There is also a need
for medicines with improved CNS efficacy, since approximately 25%
of patients with EGFR-mutated NSCLC have brain metastases at
diagnosis, increasing to approximately 40% within two years of
diagnosis.
About AstraZeneca in Lung Cancer
AstraZeneca is committed to developing medicines to help every
patient with lung cancer. We have two approved medicines and a
growing pipeline that targets genetic changes in tumour cells and
boosts the power of the immune response against cancer. Our
unrelenting pursuit of science aims to deliver more breakthrough
therapies with the goal of extending and improving the lives of
patients across all stages of disease and lines of therapy.
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 five
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 haematology.
By harnessing the power of four scientific platforms –
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates – and by championing the development
of personalised 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 commercialisation 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.
About Chi-Med
Hutchison China MediTech, known as Chi-Med, is an innovative
biopharmaceutical company which researches, develops, manufactures
and sells pharmaceuticals and healthcare products. Its Innovation
Platform, Hutchison MediPharma, 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.
For more information, please visit www.chi-med.com.
Intended audiences
This press release is issued from AstraZeneca Corporate
Headquarters in Cambridge, UK and is intended to provide
information about our global business. Please be aware that
information relating to the approval status and labels of approved
products may vary from country to country, and a country-specific
press release on this topic may have been issued in the countries
where AstraZeneca conducts business.
References
1 Ahn M-J, et al. TATTON Phase Ib Expansion Cohort: Osimertinib
Plus Savolitinib for Patients with EGFR-mutant MET-amplified NSCLC
After Progression on Prior EGFR-TKI. Abstract #8985. To be
presented at the World Lung Cancer Congress (WCLC) 2017, Yokohama,
Japan, 15-18 October 2017.
2 Yang J-J, et al. A Phase Ib Trial of Savolitinib Plus
Gefitinib for Patients with EGFR-mutant MET-amplified Advanced
NSCLC. Abstract #8995. To be presented at the World Lung Cancer
Congress (WCLC) 2017, Yokohama, Japan, 15-18 October 2017.
3 Stewart EL, et al. Known and Putative Mechanisms of Resistance
to EGFR Targeted Therapies in NSCLC Patients with EGFR Mutations—a
Review. Transl Lung Cancer Res. 2015:4(1):67–81.
4 Engelman et al. MET Amplification Leads to Gefitinib
Resistance in Lung Cancer by Activating ERBB3 Signaling. Science
2007;316:1039-1043.
5 Bean et al. MET amplification occurs with or without T790M
mutations in EGFR mutant lung tumors with acquired resistance to
gefitinib or erlotinib. Proc Natl Acad Sci USA
2007;104:20932–20937.
6 Sequist et al. Genotypic and Histological Evolution of Lung
Cancers Acquiring Resistance to EGFR Inhibitors. Science
Transitional Medicine 2011; 3(75):75ra26.
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