HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM, HKEX: 13)
and AstraZeneca PLC (“AstraZeneca”) (LON/STO/Nasdaq: AZN) today
announce that preliminary results from the SAVANNAH Phase II trial
showed that TAGRISSO® (osimertinib) plus savolitinib demonstrated
an objective response rate (“ORR”) of 49% (95% confidence interval
[“CI”], 39-59%) in patients with epidermal growth factor
receptor-mutated (“EGFRm”) non-small cell lung cancer (“NSCLC”)
with high levels of mesenchymal epithelial transition (“MET”)
overexpression and/or amplification, defined as IHC90+ and/or
FISH10+, whose disease progressed on treatment with TAGRISSO®.
The highest ORR was observed in patients with
high levels of MET who were not treated with prior chemotherapy
(52% [95% CI, 41-63%]). In patients whose tumors did not show high
levels of MET, the ORR was 9% (95% CI, 4-18%). These results are
being shared at the International Association for the Study of Lung
Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC), taking
place on August 6-9, 2022 in Vienna, Austria.
Savolitinib, marketed in China under the brand
name ORPATHYS®, is an oral, potent and highly selective MET
tyrosine kinase inhibitor (“TKI”) being jointly developed and
commercialized by AstraZeneca and HUTCHMED.
While EGFR-targeted therapy can provide a
durable survival benefit to patients with EGFRm NSCLC, most will
eventually develop resistance to their treatment, with MET being
the most common resistance biomarker.1 Among patients screened for
enrolment in SAVANNAH, all of whom experienced disease progression
on TAGRISSO®, 62% had tumors with MET overexpression and/or
amplification, and more than one-third (34%) met the defined high
MET level cut-off.
Myung-Ju Ahn, MD, PhD, Professor of
Hemato-Oncology at the Department of Medicine, Samsung Medical
Center, Sungkyunkwan University School of Medicine, Seoul, South
Korea, and Principal Investigator in the SAVANNAH Phase II trial,
said: “Acquired resistance to targeted therapy and disease
progression are difficult realities for most patients with
EGFR-mutated NSCLC. These preliminary SAVANNAH results potentially
support a novel approach for identifying patients with MET
overexpression and/or amplification who are most likely to benefit
from a MET-directed therapy, like savolitinib. They also suggest
that with the right biomarker testing strategy, MET may be a more
prevalent target among resistant patients than previously
understood, supporting further investigation of the osimertinib
plus savolitinib regimen.”
Cristian Massacesi, Chief Medical Officer and
Oncology Chief Development Officer, AstraZeneca said: “The current
standard of care for patients with EGFR-mutated lung cancer who
progress on targeted treatment is chemotherapy. The results from
SAVANNAH suggest savolitinib added to TAGRISSO® at the time of
disease progression could possibly provide these biomarker-selected
patients with a potentially less toxic, more effective treatment
option. We look forward to better understanding the potential of
the TAGRISSO® plus savolitinib regimen in this trial and in the
SAFFRON Phase III trial.”
Weiguo Su, Chief Executive Officer and Chief
Scientific Officer, HUTCHMED, said: “It is encouraging to see the
savolitinib and TAGRISSO® combination regimen progress into a
global Phase III study, SAFFRON, with a well-supported patient
selection strategy that could benefit more patients than previously
recognized. The preliminary results of the SAVANNAH study also
affirm the role of molecular testing prior to initiating subsequent
treatment for NSCLC patients who experience disease progression on
an EGFR-targeted therapy. We are aligned in pursuing a selective,
patient-centric approach in development efforts for savolitinib in
this setting.”
In this analysis, patients’ MET overexpression
and/or amplification levels were determined by two tests:
immunohistochemistry (“IHC”), which detects if cancer cells have a
particular protein or marker on their surface, and fluorescence in
situ hybridization (“FISH”), which detects a specific DNA sequence
from cancer cells. All patients in this analysis (n=193) had at
least IHC50+ and/or FISH5+, and were treated with savolitinib 300mg
once daily added to TAGRISSO® 80mg once daily following disease
progression on TAGRISSO® alone.
Summary of efficacy
resultsi:
Endpoint |
All patients (IHC50+ and/or FISH5+; n=193) |
Patients with high levels of METii(IHC90+ and/or FISH10+) |
Patients with lower levels of METii (n=77) |
All(n=108) |
No prior chemo (n=87) |
ORR, % (95% CI) |
32 (26, 39) |
49 (39, 59) |
52 (41, 63) |
9 (4, 18) |
Median DoRiii, months (95%
CI) |
8.3 (6.9, 9.7) |
9.3 (7.6, 10.6) |
9.6 (7.6, 14.9) |
6.9 (4.1, 16.9) |
Median PFSiv, months (95% CI) |
5.3 (4.2, 5.8) |
7.1 (5.3, 8.0) |
7.2 (4.7, 9.2) |
2.8 (2.6, 4.3) |
DCRv, % (95% CI) |
61 (53, 68) |
74 (65, 82) |
75 (64, 83) |
43 (32, 55) |
- Analysis data cut-off: 27 August 2021
- Eight patients excluded from subgroup analyses due to invalid
or missing test results
- DoR, duration of response
- PFS, progression-free survival
- DCR, disease control rate
The safety profile of TAGRISSO® plus savolitinib
was consistent with the known profiles of the combination and each
treatment alone. No new safety signals were identified. Less than
half (45%) of patients in this analysis experienced Grade 3 or
higher adverse events (“AEs”), with those most frequently reported
including pulmonary embolism, dyspnea, decreased neutrophil count
and pneumonia. AEs attributable to savolitinib and leading to
discontinuation occurred in 13% of patients.
The global SAFFRON Phase III trial will further
assess the TAGRISSO® plus savolitinib combination versus
platinum-based doublet chemotherapy in patients with EGFRm,
MET-overexpressed and/or amplified, locally advanced or metastatic
NSCLC following TAGRISSO®. Patients are being prospectively
selected using the high MET level cut-off identified in
SAVANNAH.
About NSCLC and MET
aberrations
Lung cancer is the leading cause of cancer death
among men and women, accounting for about one-fifth of all cancer
deaths.2 Lung cancer is broadly split into NSCLC and small cell
lung cancer, with 80-85% classified as NSCLC.3 The majority of
NSCLC patients (approximately 75%) are diagnosed with advanced
disease and approximately 10-15% of NSCLC patients in the U.S. and
Europe and 30-40% of patients in Asia have EGFRm NSCLC.4,5,6,7
MET is a tyrosine kinase receptor that has an
essential role in normal cell development.8 MET overexpression
and/or amplification can lead to tumor growth and the metastatic
progression of cancer cells, and is the primary mechanism of
acquired resistance to EGFR TKIs for metastatic EGFR-mutated NSCLC.
8,9 The prevalence of MET depends on the sample type, detection
method and assay cut-off used.10
About SAVANNAH
SAVANNAH is an ongoing global, randomized,
single-arm Phase II trial studying the efficacy of savolitinib
added to TAGRISSO® in patients with EGFRm, locally advanced or
metastatic NSCLC with MET overexpression and/or amplification who
progressed following treatment with TAGRISSO®. Patients were
treated with savolitinib 300 or 600 mg once-daily (QD) or 300 mg
twice-daily, in combination with oral osimertinib 80 mg QD.
The trial has enrolled 294 patients to date in
more than 80 centers globally, including centers in the U.S.,
Canada, Europe, South America and Asia. The primary endpoint is
ORR. Key secondary endpoints include PFS, DoR and safety.
About
TAGRISSO®
TAGRISSO® (osimertinib) is a third-generation,
irreversible EGFR-TKI with proven clinical activity in NSCLC,
including against central nervous system metastases. TAGRISSO®
(40mg and 80mg once-daily oral tablets) has been used to treat
approximately 575,000 patients across indications worldwide and
AstraZeneca continues to explore TAGRISSO® as a treatment for
patients across multiple stages of EGFRm NSCLC.
In Phase III trials, TAGRISSO® is being
investigated in the neoadjuvant resectable setting (NeoADAURA), in
the Stage IA2-IA3 adjuvant resectable setting (ADAURA2), in the
Stage III locally advanced unresectable setting following
chemoradiation therapy (LAURA), and in combination with
chemotherapy in the advanced setting (FLAURA2). AstraZeneca is also
researching ways to address tumor mechanisms of resistance through
the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III
trial, which test TAGRISSO® given concomitantly with savolitinib,
an oral, potent and highly selective MET TKI, as well as other
potential new medicines.
About Savolitinib
Savolitinib is an oral, potent and highly
selective MET TKI that has demonstrated clinical activity in
advanced solid tumors. It blocks atypical activation of the MET
receptor tyrosine kinase pathway that occurs because of mutations
(such as exon 14 skipping alterations or other point mutations),
gene amplification or protein overexpression.
Savolitinib is marketed in China under the brand
name ORPATHYS® for the treatment of patients with NSCLC with MET
exon 14 skipping alterations who have progressed following prior
systemic therapy or are unable to receive chemotherapy. It is
currently under clinical development for multiple tumor types,
including lung, kidney and gastric cancers, as a single treatment
and in combination with other medicines.
About AstraZeneca and HUTCHMED
collaboration
In 2011, AstraZeneca and HUTCHMED entered a
global licensing and collaboration agreement to jointly develop and
commercialize savolitinib. Joint development of savolitinib in
China is led by HUTCHMED, while AstraZeneca leads development
outside of China. HUTCHMED is responsible for the marketing
authorization, manufacturing and supply of savolitinib in China.
AstraZeneca is responsible for the commercialization of savolitinib
in China and worldwide. Sales of savolitinib are recognized by
AstraZeneca.
About AstraZeneca in lung
cancer
AstraZeneca is working to bring patients with
lung cancer closer to cure through the detection and treatment of
early-stage disease, while also pushing the boundaries of science
to improve outcomes in the resistant and advanced settings. By
defining new therapeutic targets and assessing innovative
approaches, the Company aims to match medicines to the patients who
can benefit most.
The Company’s comprehensive portfolio includes
leading lung cancer medicines and the next wave of innovations
including TAGRISSO® (osimertinib) and IRESSA® (gefitinib); IMFINZI®
(durvalumab) and tremelimumab; ENHERTU® (trastuzumab deruxtecan)
and datopotamab deruxtecan in collaboration with Daiichi Sankyo;
ORPATHYS® (savolitinib) in collaboration with HUTCHMED; as well as
a pipeline of potential new medicines and combinations across
diverse mechanisms of action.
AstraZeneca is a founding member of the Lung
Ambition Alliance, a global coalition working to accelerate
innovation and deliver meaningful improvements for people with lung
cancer, including and beyond treatment.
About AstraZeneca in
oncology
AstraZeneca is leading a revolution in oncology
with the ambition to provide cures for cancer in every form,
following the science to understand cancer and all its complexities
to discover, develop and deliver life-changing medicines to
patients.
The Company's focus is on some of the most
challenging cancers. It is through persistent innovation that
AstraZeneca has built one of the most diverse portfolios and
pipelines in the industry, with the potential to catalyze changes
in the practice of medicine and transform the patient
experience.
AstraZeneca has the vision to redefine cancer
care and, one day, eliminate cancer as a cause of death.
About AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global,
science-led biopharmaceutical company that focuses on the
discovery, development, and commercialization of prescription
medicines in Oncology, Rare Diseases, and BioPharmaceuticals,
including Cardiovascular, Renal & Metabolism, and Respiratory
& Immunology. Based in Cambridge, UK, AstraZeneca operates in
over 100 countries and its innovative medicines are used by
millions of patients worldwide. Please visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
About HUTCHMED
HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an
innovative, commercial-stage, biopharmaceutical company. It is
committed to the discovery and global development and
commercialization of targeted therapies and immunotherapies for the
treatment of cancer and immunological diseases. It has more than
4,900 personnel across all its companies, at the center of which is
a team of about 1,800 in oncology/immunology. Since inception it
has advanced 13 cancer drug candidates from in-house discovery into
clinical studies around the world, with its first three oncology
drugs now approved and marketed in China. For more information,
please visit: www.hutch-med.com or follow us on LinkedIn.
References
1. |
|
Del MD, et al. Understanding the Mechanisms of Resistance in
EGFR-Positive NSCLC: From Tissue to Liquid Biopsy to Guide
Treatment Strategy. Int J Mol Sci. 2019;20(16): 3951. |
2. |
|
World Health Organization.
International Agency for Research on Cancer. All cancers fact
sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/39-All-cancers-fact-sheet.pdf.
Accessed July 2022. |
3. |
|
American Cancer Society. What is
Lung Cancer? Available at:
https://www.cancer.org/cancer/lung-cancer/about/what-is.html.
Accessed July 2022. |
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Knight SB, et al. Progress and
prospects of early detection in lung cancer. Open Biol. 2017;7(9):
170070. |
5. |
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Keedy VL, et al. American Society
of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth
Factor Receptor (EGFR) Mutation Testing for Patients with Advanced
Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine
Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27. |
6. |
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Zhang Y, et al. The prevalence of
EGFR mutation in patients with non-small cell lung cancer: a
systematic review and meta-analysis. Oncotarget. 2016;7(48). |
7. |
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Szumera-Ciećkiewicz A, et
al. EGFR Mutation Testing on Cytological and Histological Samples
in 11. Non-Small Cell Lung Cancer: a Polish, Single Institution
Study and Systematic Review of European Incidence. Int J Clin Exp
Pathol. 2013:6;2800-12. |
8. |
|
Uchikawa E, et al. Structural
basis of the activation of c-MET receptor. Nat Commun.
2021;12(4074). |
9. |
|
Wang Q, et al. MET inhibitors for
targeted therapy of EGFR TKI-resistant lung cancer. Journal of
Hematology & Oncology. 2019;63. |
10. |
|
Coleman N, et al. Beyond
epidermal growth factor receptor: MET amplification as a general
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non-small-cell lung cancer. ESMO Open. 2019;6(6). |
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 HUTCHMED’s current expectations
regarding future events, including its expectations regarding the
therapeutic potential of savolitinib for the treatment of patients
with NSCLC, the further clinical development of savolitinib in this
and other indications, its expectations as to whether clinical
studies of savolitinib 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
the sufficiency of HUTCHMED’s data to support New Drug Application
approval of savolitinib for the treatment of patients with NSCLC in
China, the U.S., E.U., Japan or other jurisdictions, the safety
profile of savolitinib, the potential for savolitinib to become a
new standard of care for patients with NSCLC and other types of
cancer, its ability to implement and complete its further clinical
development plans for savolitinib, the potential commercial launch
of savolitinib in the U.S., E.U., Japan, China and other
jurisdictions, the timing of these events, and the impact of the
COVID-19 pandemic on general economic, regulatory and political
conditions. In addition, as certain studies rely on the use of
TAGRISSO® and IMFINZI® as combination therapeutics with
savolitinib, such risks and uncertainties include assumptions
regarding the safety, efficacy, supply and continued regulatory
approval of TAGRISSO® and IMFINZI®. 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 HUTCHMED’s
filings with the U.S. Securities and Exchange Commission, on AIM
and with The Stock Exchange of Hong Kong Limited. HUTCHMED
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.
AstraZeneca Contacts
For details on how to contact the Investor
Relations Team, please click here. For Media contacts, click
here.
HUTCHMED Contacts
Investor Enquiries |
|
Mark Lee, Senior Vice President |
+852 2121 8200 |
Annie Cheng, Vice President |
+1 (973) 567 3786 |
|
|
Media Enquiries |
|
Americas – Brad Miles, Solebury Trout |
+1 (917) 570 7340 (Mobile)
bmiles@troutgroup.com |
Europe – Ben Atwell / Alex Shaw,
FTI Consulting |
+44 20 3727 1030 /
+44 7771 913 902 (Mobile) /
+44 7779 545 055 (Mobile)
HUTCHMED@fticonsulting.com |
Asia – Zhou Yi, Brunswick |
+852 9783 6894 (Mobile)
HUTCHMED@brunswickgroup.com |
|
|
Nominated Advisor |
|
Atholl Tweedie / Freddy Crossley, Panmure Gordon
(UK) Limited |
+44 (20) 7886 2500 |
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