HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13)
and AstraZeneca PLC (“AstraZeneca”) (LSE/STO/Nasdaq:AZN) have
initiated SACHI, a China Phase III study of ORPATHYS®
(savolitinib), an oral, potent, and highly selective MET tyrosine
kinase inhibitor (“TKI”), in combination with AstraZeneca’s
third-generation, irreversible epidermal growth factor receptor
(“EGFR”) TKI, TAGRISSO® (osimertinib). The first patient received
their first dose on November 22, 2021.
The Phase III trial is a multi-center,
open-label, randomized, controlled study in patients with locally
advanced or metastatic EGFR mutation-positive non-small cell lung
cancer (“NSCLC”) with MET amplification after disease progression
on EGFR inhibitor therapy. The study will evaluate the efficacy and
safety of ORPATHYS® in combination with TAGRISSO®, compared to
platinum-based doublet-chemotherapy (pemetrexed plus cisplatin or
carboplatin), the standard-of-care treatment option in this
setting. The primary endpoint of the study is median progression
free survival (“PFS”) as assessed by investigators. Other endpoints
include median PFS assessed by an independent review committee,
median overall survival (“OS”), objective response rate (“ORR”),
duration of response (“DoR”), disease control rate (“DCR”), time to
response (TTR), and safety. Additional details may be found at
clinicaltrials.gov, using identifier NCT05015608.
About NSCLC, EGFR 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 More than a third of the world’s lung cancer patients are
in China.3 Lung cancer is broadly split into NSCLC and small cell
lung cancer, with 80-85% classified as NSCLC.4 The majority of
NSCLC patients are diagnosed with advanced disease while
approximately 25-30% present with resectable disease at
diagnosis.5,6 For patients with resectable tumors, the majority of
patients eventually develop recurrence despite complete tumor
resection and adjuvant chemotherapy.7
Approximately 10-25% of NSCLC patients in the US
and Europe, and 30-40% of patients in Asia have EGFR-mutated
NSCLC.8,9,10 These patients are particularly sensitive to treatment
with an EGFR TKI which blocks the cell-signaling pathways that
drive the growth of tumor cells.11
MET is a tyrosine kinase receptor.12 Aberration
of MET (amplification or overexpression) is present in both
treatment naïve patients as well as being one of the primary
mechanisms of acquired resistance to EGFR TKIs for metastatic
EGFR-mutated NSCLC.13,14
About Savolitinib
(ORPATHYS® in China)
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) or
gene amplification.
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.
In 2011, following its discovery and initial
development by HUTCHMED, AstraZeneca and HUTCHMED entered a global
licensing agreement to jointly develop and commercialize
savolitinib. Joint development 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.
Savolitinib development in
NSCLC
Phase II study of savolitinib monotherapy in MET
Exon 14 skipping alteration NSCLC (NCT02897479) – In June 2021,
savolitinib was granted drug registration conditional approval by
the National Medical Products Administration of China (NMPA) for
MET Exon 14 skipping alteration NSCLC. The approval was based on
the results of a Phase II study in China; results of this study
were published in The Lancet Respiratory Medicine15. At a median
follow up of 17.6 months, savolitinib demonstrated an ORR of 42.9%
(95% confidence interval [CI] 31.1-55.3) and median PFS of 6.8
months (95% CI 4.2-9.6) in the overall trial population. DCR in the
overall trial population was 82.9% (95% CI 72.0-90.8). The safety
and tolerability profile of savolitinib was consistent with
previous trials, and no new safety signals were identified.
Continued approval is contingent upon the successful completion of
a confirmatory trial in this patient population (NCT04923945).
TATTON Phase Ib/II expansion studies of
savolitinib in combination with TAGRISSO® in patients who have
progressed following EGFR TKI treatment due to MET amplification
(NCT02143466) – This global exploratory study in over 220 EGFR
mutation positive NSCLC patients with MET amplified tumors
following progression after treatment with any EGFR TKI. Results
were published in Lancet Oncology16 and final analysis was
presented at the World Conference on Lung Cancer1. Three cohorts
with patients treated following progression on first- or
second-generation EGFR TKI demonstrated an ORR of 64.7-66.7% and a
median PFS of 9.0-11.1 months. The cohort of patients treated
following progression on a third-generation EGFR TKI demonstrated
an ORR of 33.3% (95% CI 22.4-45.7), with a median PFS of 5.5 months
(95% CI 4.1-7.7). The combination demonstrated encouraging
anti-tumor activity and an acceptable risk-benefit profile.
SAVANNAH Phase II study of savolitinib in
combination with TAGRISSO® in patients who have progressed
following TAGRISSO® due to MET amplification or overexpression
(NCT03778229) – This is a single-arm, open-label, global study in
epidermal growth factor receptor (“EGFR”) mutation positive NSCLC
patients with MET amplified/overexpressed tumors following
progression after treatment with TAGRISSO®, an EGFR TKI owned by
AstraZeneca.
SACHI Phase III study of savolitinib in
combination with TAGRISSO® in patients who have progressed
following EGFR TKI treatment due to MET amplification (NCT05015608)
– This is a randomized, open-label study in China in EGFR mutation
positive NSCLC patients with MET amplified tumors following
progression after treatment with any EGFR TKI.
SANOVO Phase III study of savolitinib in
combination with TAGRISSO® in treatment-naïve patients with EGFR
mutant positive NSCLC with MET overexpression (NCT05009836) – This
is a randomized, blinded study in China in untreated, unresectable
or metastatic patients with EGFR mutation positive NSCLC with MET
positive tumors.
Savolitinib development in kidney
cancer
SAVOIR randomized, controlled study of
savolitinib monotherapy in MET-driven papillary renal cell
carcinoma (“RCC”) (NCT03091192) – In May 2020, data from 60
patients in this global study of savolitinib monotherapy compared
with sunitinib monotherapy in MET-driven papillary RCC was
presented at the ASCO 2020 Program and published simultaneously in
JAMA Oncology17. Savolitinib demonstrated encouraging activity,
including an ORR of 27% versus 7% for sunitinib, with no
savolitinib responding patients experiencing disease progression at
data cut-off, and an encouraging OS hazard ratio of 0.51 (95% CI:
0.21–1.17; p=0.110) with median not reached at data cut-off.
CALYPSO Phase I/II study of savolitinib in
combination with IMFINZI® PD-L1 inhibitor in RCC (NCT02819596) –
The CALYPSO study is an investigator initiated open-label Phase
I/II study of savolitinib in combination with IMFINZI®, a PD-L1
antibody owned by AstraZeneca. The study is evaluating the safety
and efficacy of the savolitinib/IMFINZI® combination in patients
with papillary RCC and clear cell RCC. An analysis of 41 patients
enrolled in the papillary RCC cohort of in this study was presented
at the 2021 ASCO Annual Meeting18, showing a confirmed response
rate in 8 out of the 14 MET-driven patients, or 57%, with a median
DoR of 9.4 months, median PFS of 10.5 months and median OS of 27.4
months. No new safety signals were seen.
SAMETA Phase III study in combination with
IMFINZI® PD-L1 inhibitor in MET-driven, unresectable and locally
advanced or metastatic papillary RCC (NCT05043090) – Based on the
encouraging results of the SAVOIR and CALYPSO studies, we have
initiated SAMETA, a global Phase III, open-label, randomized,
controlled study of savolitinib plus IMFINZI® versus sunitinib
monotherapy versus IMFINZI® monotherapy in patients with
MET-driven, unresectable and locally advanced or metastatic
papillary RCC.
Savolitinib development in gastric
cancer
Phase II study of savolitinib monotherapy in
advanced or metastatic MET amplified gastric cancer (“GC”) or
adenocarcinoma of the gastroesophageal junction (“GEJ”)
(NCT04923932) – This is an open-label, two-cohort, multi-center
study to evaluate the efficacy, safety and pharmacokinetics (PK) of
savolitinib in locally advanced or metastatic GC or GEJ patients
whose disease progressed after at least one line of standard
therapy.
This trial follows multiple Phase II studies
that have been conducted in Asia to study savolitinib in MET-driven
GC patients, including VIKTORY.19 VIKTORY is an
investigator-initiated Phase II umbrella study in GC in South Korea
in which a total of 715 patients were successfully sequenced into
molecular-driven patient groups, including those with MET amplified
GC. Patients whose tumors harbor MET amplification were treated
with savolitinib monotherapy, reporting an ORR of 50% (10/20, 95%
CI: 28.0, 71.9).
Savolitinib development in other cancer
indications
Savolitinib opportunities are also continuing to
be explored in multiple other MET-driven tumor settings via
investigator-initiated studies including colorectal cancer.
About
TAGRISSO®
TAGRISSO® (osimertinib) is a third-generation,
irreversible EGFR TKI with clinical activity against central
nervous system metastases. TAGRISSO® (40mg and 80mg once-daily oral
tablets) has been used to treat more than 485,000 patients across
indications worldwide and AstraZeneca continues to explore
TAGRISSO® as a treatment for patients across multiple stages of
EGFR-mutated NSCLC.
In Phase III trials, TAGRISSO® is being tested
in the neoadjuvant resectable setting (NeoADAURA), in the Stage III
locally advanced unresectable setting (LAURA) and, in combination
with chemotherapy, in the Stage III locally advanced or Stage IV
metastatic settings (FLAURA2). AstraZeneca is also researching ways
to address tumor mechanisms of resistance through the SACHI and
SANOVO Phase III trials, as well as the SAVANNAH and ORCHARD Phase
II trials, which test TAGRISSO® given concomitantly with
savolitinib, (ORPATHYS® in China), as well as other potential new
medicines.
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
4,500 personnel across all its companies, at the center of which is
a team of over 1,400 in oncology/immunology. Since inception it has
advanced eleven cancer drug candidates from in-house discovery into
clinical studies around the world, with its first three oncology
drugs now approved and marketed. For more information, please
visit: www.hutch-med.com or follow us on LinkedIn.
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 its data to support New Drug Application
approval of savolitinib for the treatment of patients with NSCLC in
China, its potential to gain expeditious approvals for savolitinib
in other jurisdictions such as E.U. or Japan, the safety profile of
savolitinib the potential for savolitinib to become a new standard
of care for NSCLC patients, its ability to implement and complete
its further clinical development plans for savolitinib its
potential commercial launch 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.
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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doi:10.1016/S1470-2045(19)30785-5.17 Choueiri TK, et al.
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2021) 4511-4511. doi: 10.1200/JCO.2021.39.15_suppl.4511.19 Lee
J, et al. Tumor Genomic Profiling Guides Patients with Metastatic
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10.1158/2159-8290.CD-19-0442.
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