REG - Hutchmed China Ltd - SAVANNAH: clinically meaningful response rate

HUTCHMED (China)Announcement

16/10/2024 07:00

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RNS Number : 3896I  Hutchmed (China) Limited  16 October 2024

HUTCHMED Announces that TAGRISSO(®) plus ORPATHYS(®) demonstrated high, clinically meaningful response rate in lung cancer patients with high levels of MET overexpression and/or amplification in SAVANNAH Phase II trial

 

- New data demonstrate efficacy for the oral treatment combination to address
MET-driven resistance in EGFR-mutated lung cancer -

- MET is a common biomarker in this setting for patients who develop
resistance to EGFR targeted therapies -

Hong Kong, Shanghai & Florham Park, NJ - Wednesday, October 16, 2024:
HUTCHMED (China) Limited ("HUTCHMED (https://www.hutch-med.com/) ")
(Nasdaq/AIM:HCM; HKEX:13) today announces positive high-level results from the
SAVANNAH Phase II trial that showed TAGRISSO(®) (osimertinib) plus
ORPATHYS(®) (savolitinib) demonstrated a high, clinically meaningful and
durable objective response rate ("ORR") for patients with epidermal growth
factor receptor-mutated ("EGFRm") non-small cell lung cancer ("NSCLC") with
high levels of MET overexpression and/or amplification, defined as IHC90+
and/or FISH10+, whose disease progressed on treatment with TAGRISSO(®). These
data will be presented at a forthcoming medical meeting and shared with global
regulatory authorities. In 2023, TAGRISSO(®) plus ORPATHYS(®) received Fast
Track designation from the US Food and Drug Administration (FDA) in this
setting.

 

ORPATHYS(®) is an oral, potent, and highly selective MET tyrosine kinase
inhibitor ("TKI") being jointly developed by AstraZeneca and HUTCHMED and
commercialized by AstraZeneca. It is approved in China 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.

 

While EGFR-targeted therapy can provide a substantial survival benefit to
patients with EGFRm NSCLC, most will eventually develop resistance to their
treatment, with MET being a common resistance biomarker. 1  Among patients
screened for enrollment in SAVANNAH, an estimated 62% had tumors with MET
overexpression and/or amplification, and approximately 34% met the defined
high MET level cut-off upon clinical progression.

 

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: "Osimertinib can provide patients with EGFR-mutated lung cancer
unprecedented survival and has transformed the treatment landscape, but
patients can develop resistance due to genes like MET - a common resistance
biomarker. These results show that adding savolitinib, a selective
MET-inhibitor, while continuing osimertinib treatment helped to deliver a
meaningful response among patients whose disease progressed, providing a
potential new treatment option following standard-of-care osimertinib."

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "These positive SAVANNAH results show the benefit of a targeted
treatment approach in EGFR-mutated lung cancer patients who experience
MET-driven resistance. The improved response rates from ORPATHYS(®) added to
TAGRISSO(®), which is the backbone EGFR-mutated lung cancer therapy,
reinforce the importance of identifying MET aberration and validate our
combination strategy to address resistance while allowing continued
TAGRISSO(®) treatment."

 

Weiguo Su, Chief Executive Officer and Chief Scientific Officer, HUTCHMED,
said: "Previous results from the SAVANNAH Phase II trial provided a novel
biomarker approach for identifying patients with MET overexpression and/or
amplification who are most likely to benefit from a MET-directed therapy, an
existing unmet need. These new, positive results affirm our selective,
patient-centric approach, which could allow us to deliver the first
biomarker-driven targeted therapy combination option in this setting."

 

The safety and tolerability of TAGRISSO(®) plus ORPATHYS(®) was consistent
with the known safety profiles of the combination and each treatment alone. No
new safety signals were identified.

 

In August 2022,
(https://www.astrazeneca.com/media-centre/press-releases/2022/tagrisso-plus-savolitinib-demonstrated-49-objective-response-rate-in-lung-cancer-patients-in-savannah-phase-ii-trial.html)
initial positive ORR results from the SAVANNAH trial were presented at the
International Association for the Study of Lung Cancer 2022 World Conference
on Lung Cancer (WCLC).

 

The global SAFFRON Phase III trial sponsored by AstraZeneca will further
assess the TAGRISSO(®) plus ORPATHYS(®) 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 both men and women,
accounting for about one-fifth of all cancer deaths. 2 (,) 3  Lung cancer is
broadly split into NSCLC and small cell lung cancer. 4  Each year there are an
estimated 2.4 million people diagnosed with lung cancer globally, with 80-85%
of patients diagnosed with NSCLC, the most common form of lung
cancer.(2)(,)(4)(,) 5  Approximately 10-15% of NSCLC patients in the US and
Europe, and 30-40% of patients in Asia have EGFRm NSCLC. 6 (,) 7 (,) 8 

 

MET is a tyrosine kinase receptor that has an essential role in normal cell
development. 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 EGFRm NSCLC. Among patients
who experience disease progression post-osimertinib treatment, approximately
15-50% present with MET aberration. 9 (,) 10 (,) 11 (,) 12 (,) 13  The
prevalence of MET depends on the sample type, detection method and assay
cut-off used. 14 

 

About SAVANNAH

SAVANNAH is an ongoing global, randomised, Phase II trial sponsored by
AstraZeneca studying the efficacy of ORPATHYS(®) added to TAGRISSO(®) in
patients with EGFRm, locally advanced or metastatic NSCLC with MET
overexpression and/or amplification who progressed following treatment with
TAGRISSO(®). Based on the original single-arm trial design, patients were
treated with ORPATHYS(®) 300 or 600 mg once-daily (QD) or 300 mg twice-daily,
in combination with oral TAGRISSO(®) 80 mg QD. In 2022, a registrational
component was added to the trial that compared ORPATHYS(®) 300 mg twice-daily
and TAGRISSO(®) 80 mg QD to ORPATHYS(®) 300 mg twice-daily and placebo.

 

The trial enrolled over 360 patients in more than 80 centers globally,
including in North America, Europe, South America and Asia. The primary
endpoint is ORR and key secondary endpoints include progression-free survival
and duration of response.

 

About TAGRISSO(®)

TAGRISSO(®) (osimertinib) is a third-generation, irreversible EGFR-TKI with
proven clinical activity in NSCLC, including against central nervous system
(CNS) metastases. TAGRISSO(®) (40mg and 80mg once-daily oral tablets) has
been used to treat nearly 800,000 patients across its indications worldwide
and AstraZeneca continues to explore TAGRISSO(®) as a treatment for patients
across multiple stages of EGFRm NSCLC.

 

There is an extensive body of evidence supporting the use of TAGRISSO(®) as
standard of care in EGFRm NSCLC. TAGRISSO(®) improved patient outcomes in
early-stage disease in the ADAURA Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2023/tagrisso-demonstrated-strong-overall-survival-benefit-in-the-adaura-phase-iii-trial.html)
, locally advanced disease in the LAURA Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-improved-pfs-in-stage-iii-lung-cancer.html)
, late-stage disease in the FLAURA Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2019/tagrisso-significantly-improves-overall-survival-in-the-phase-iii-flaura-trial-for-1st-line-egfr-mutated-non-small-cell-lung-cancer-09082019.html)
, and with chemotherapy in the FLAURA2 Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2023/tagrisso-plus-chemotherapy-extended-median-progression-free-survival-by-nearly-9-months-in-egfr-mutated-advanced-lung-cancer-in-flaura2-phase-iii-trial.html)
.

 

About ORPATHYS(®)

ORPATHYS(®) (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.

 

It is approved in China 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 the first selective MET inhibitor
approved in China and the first in the National Reimbursement Drug List of
China (NRDL).

 

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. In addition to SAVANNAH and SAFFRON, in China the
combination of savolitinib and osimertinib in lung cancer is also being
studied in the SACHI and SANOVO Phase III trials.

 

About HUTCHMED

HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage,
biopharmaceutical company. It is committed to the discovery, global
development and commercialization of targeted therapies and immunotherapies
for the treatment of cancer and immunological diseases. It has approximately
5,000 personnel across all its companies, at the center of which is a team of
about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on
bringing cancer drug candidates from in-house discovery to patients around the
world, with its first three medicines marketed in China, the first of which is
also approved in the US, Europe and Japan. For more information, please visit
www.hutch‑med.com (https://www.hutch-med.com/) or follow us on LinkedIn
(https://www.linkedin.com/company/hutchmed/) .

 

Forward-Looking Statements

This announcement 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 HUTCHMED's current
expectations regarding future events, including its expectations regarding the
therapeutic potential of savolitinib, the further clinical development for
savolitinib, its expectations as to whether any studies on 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 enrollment
rates and the 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
savolitinib, including as a combination therapy, to meet the primary or
secondary endpoint of a study, to obtain regulatory approval in different
jurisdictions and to gain commercial acceptance after obtaining regulatory
approval; the potential market of savolitinib for a targeted indication; and
the sufficiency of funding; and AstraZeneca's ability to successfully develop
and commercialize savolitinib.. In addition, as certain studies rely on the
use of other drug products such as osimertinib as combination therapeutics
with savolitinib, such risks and uncertainties include assumptions regarding
the safety, efficacy, supply and continued regulatory approval of these
therapeutics. 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 US Securities and Exchange Commission, The Stock Exchange of
Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or
revise the information contained in this announcement, whether as a result of
new information, future events or circumstances or otherwise.

Medical Information

This announcement contains information about products that may not be
available in all countries, or may be available under different trademarks,
for different indications, in different dosages, or in different strengths.
Nothing contained herein should be considered a solicitation, promotion or
advertisement for any prescription drugs including the ones under development.

Inside Information

This announcement contains inside information for the purposes of Article 7 of
Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in
the European Union (Withdrawal) Act 2018).

 

CONTACTS
 Investor Enquiries                                                        +852 2121 8200 / ir@hutch-med.com (mailto:ir@hutch-med.com)

 Media Enquiries
 Ben Atwell / Alex Shaw, FTI Consulting                                    +44 20 3727 1030 / +44 7771 913 902 (Mobile) /
                                                                           +44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.com
                                                                           (mailto:HUTCHMED@fticonsulting.com)
 Zhou Yi, Brunswick                                                        +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com
                                                                           (mailto:HUTCHMED@brunswickgroup.com)

 Nominated Advisor
 Atholl Tweedie / Freddy Crossley / Rupert Dearden, Panmure Liberum        +44 (20) 7886 2500

 

 1    Del Re M, 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. Lung Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf
(https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf)
. Accessed September 2024.

 3  World Health Organization. International Agency for Research on Cancer.
World Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf
(https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf)
. Accessed October 2024.

 4    LUNGevity Foundation. Types of Lung Cancer. Available at:
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer
(https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer)
. Accessed September 2024.

 5    Cheema PK, et al. Perspectives on treatment advances for stage III
locally advanced unresectable non-small-cell lung cancer. Curr Oncol.
2019;26(1):37-42.

 6    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.

 7    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    Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of
Available Methods and Their Use for Analysis of Tumour Tissue and Cytology
Samples. J Clin Pathol. 2013;66:79-89.

 9    Soria JC, et al. Osimertinib in Untreated EGFR-Mutated Advanced
Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113-125.

 10  Mok TS, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive
Lung Cancer. N Engl J Med. 2017;376(7):629-640.

 11  Hartmaier R, et al. Tumor genomics in patients (pts) with advanced
epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer
(NSCLC) whose disease has progressed on first-line (1L) osimertinib therapy in
the Phase II ORCHARD study. Cancer Res 15 June 2022; 82
(12_Supplement): LB078.

 12  Piotrowska, et al.  MET amplification (amp) as a resistance mechanism to
osimertinib. Journal of Clinical Oncology 2017 35:15_suppl, 9020-9020.

 13  Hartmaier, et al. Detection of MET-mediated EGFR tyrosine kinase
inhibitor (TKI) resistance in advanced non-small cell lung cancer (NSCLC):
biomarker analysis of the TATTON study. Cancer Res (2019) 79 (13_Supplement):
4897.

 14  Coleman N, et al. Beyond epidermal growth factor receptor: MET
amplification as a general resistance driver to targeted therapy in
oncogene-driven non-small-cell lung cancer. ESMO Open. 2019;6(6).

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