TIDMHCM
Hutchmed (China) Limited
28 July 2021
Press Release
HUTCHMED and AstraZeneca Initiate Phase II Trial of ORPATHYS(R)
in Patients with MET Amplified Gastric Cancer
- Follows multiple Phase II studies of ORPATHYS(R) in Asia
including VIKTORY, which reported an 50% objective response rate
(ORR) in gastric cancer patients whose tumors harbor MET
amplification -
Hong Kong, Shanghai & Florham Park, NJ - Wednesday, July 28,
2021: HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM;
HKEX:13) and AstraZeneca PLC ("AstraZeneca") (LSE/STO/Nasdaq: AZN)
have initiated a Phase II study of ORPATHYS(R) (savolitinib), an
oral, potent, and highly selective small molecule inhibitor of MET,
a receptor tyrosine kinase, in patients with advanced or metastatic
MET amplified gastric cancer ("GC") or adenocarcinoma of the
gastroesophageal junction ("GEJ"). The first patient was dosed on
July 27, 2021.
The Phase II trial is an open-label, two-cohort, multi-center
study to evaluate the efficacy, safety and pharmacokinetics ("PK")
of ORPATHYS(R) in locally advanced or metastatic GC or GEJ patients
whose disease progressed after at least one line of standard
therapy. The primary endpoint is objective response rate ("ORR") as
assessed by an independent review committee. Other endpoints
include 12-week and 6-month progression-free survival ("PFS")
rates, median PFS, duration of response ("DoR"), disease control
rate ("DCR"), median overall survival ("OS"), safety, PK and
quality of life.
The Beijing Cancer Hospital is the lead institution of this
study. The lead investigator is Dr Shen Lin. For more information,
please see clinicaltrials.gov identifier: NCT04923932.
MET-driven gastric cancer has a very poor prognosis.[1] This
trial follows multiple Phase II studies that have been conducted in
Asia to study ORPATHYS(R) in MET-driven gastric cancer patients,
including VIKTORY.(2) VIKTORY is an investigator initiated Phase II
umbrella study in gastric cancer in South Korea in which a total of
715 patients were successfully sequenced into molecular-driven
patient groups, including those with MET amplified gastric cancer.
Patients whose tumors harbor MET amplification were treated with
ORPATHYS(R) monotherapy, reporting an ORR of 50% (10/20, 95% CI:
28.0, 71.9).
It is estimated that MET amplification accounts for
approximately 4-6% of GC patients.[2](,[3]) The annual incidence of
MET amplification GC is estimated to be approximately 24,000 in
China.[4]
About ORPATHYS(R)
ORPATHYS(R) is an oral, potent, and highly selective MET
tyrosine kinase inhibitor ("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.
ORPATHYS(R) is marketed in China for the treatment of patients
with non-small cell lung cancer ("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 ORPATHYS(R) . 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 ORPATHYS(R) in
China. AstraZeneca is responsible for the commercialization of
ORPATHYS(R) in China and worldwide. Sales of ORPATHYS(R) will be
recognized by AstraZeneca.
ORPATHYS(R) development in NSCLC
Phase II study of ORPATHYS(R) monotherapy in MET Exon 14
skipping alteration NSCLC ( NCT02897479 ) - In June 2021,
ORPATHYS(R) 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 presented during the American Society of Clinical Oncology
ASCO20 Virtual Scientific Program in May 2020, and updated results
were published in The Lancet Respiratory Medicine[5] in June 2021.
At a median follow up of 17.6 months, ORPATHYS (R) demonstrated an
objective response rate ("ORR") of 42.9% (95% confidence interval
[CI] 31.1-55.3) and median progression-free survival ("PFS") of 6.8
months (95% CI 4.2-9.6) in the overall trial population. PFS was
clinically meaningful across subgroups, and ORR results were
consistent regardless of prior treatment or tumor histology,
including in patients with the pulmonary sarcomatoid carcinoma
(PSC) subtype (40.0%, 95% CI 21.1-61.3) and patients with other
NSCLC subtypes (44.4%, 95% CI 29.6-60.0). Disease control rate
("DCR") in the overall trial population was 82.9% (95% CI
72.0-90.8). The safety and tolerability profile of ORPATHYS (R) 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).
SAVANNAH Phase II study of ORPATHYS(R) in combination with
TAGRISSO (R) in patients who have progressed following TAGRISSO(R)
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(R) , an EGFR TKI owned by AstraZeneca.
Phase III study of ORPATHYS(R) in combination with TAGRISSO(R)
in patients who have progressed following EGFR TKI treatment due to
MET amplification (in planning) - 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.
Phase III study of ORPATHYS(R) in combination with TAGRISSO(R)
in treatment naïve patients with EGFR mutant positive NSCLC with
MET overexpression (in planning) - This is a randomized, blinded
study in China in untreated, unresectable or metastatic patients
with EGFR mutation positive NSCLC with MET positive tumors.
ORPATHYS(R) development in kidney cancer
SAVOIR randomized, controlled study of ORPATHYS(R) monotherapy
in MET-driven papillary renal cell carcinoma ("RCC") ( NCT03091192
) - In May 2020, data from 60 patients in this global study of
ORPATHYS(R) monotherapy compared with sunitinib monotherapy in
MET-driven papillary RCC was presented at the ASCO 2020 Program and
published simultaneously in JAMA Oncology[6] . ORPATHYS(R)
demonstrated encouraging activity, including an ORR of 27% versus
7% for sunitinib, with no ORPATHYS(R) responding patients
experiencing disease progression at data cut-off, and an
encouraging overall survival ("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 ORPATHYS(R) in combination with
IMFINZI(R) PD-L1 inhibitor in RCC ( NCT02819596 ) - The CALYPSO
study is an investigator initiated open-label Phase I/II study of
ORPATHYS(R) in combination with IMFINZI(R) , a PD-L1 antibody owned
by AstraZeneca. The study is evaluating the safety and efficacy of
the ORPATHYS(R) /IMFINZI(R) combination in patients with papillary
RCC and clear cell RCC. An analysis of 41 patients enrolled in the
PRCC cohort of in this study was presented at the 2021 ASCO Annual
Meeting[7] , showing a confirmed response rate in 14 MET-driven
patients of 57%, with a median duration of response ("DoR") of 9.4
months, median PFS of 10.5 months and median OS of 27.4 months. No
new safety signals were seen.
Phase III study in combination with IMFINZI(R) PD-L1 inhibitor
in MET-driven, unresectable and locally advanced or metastatic PRCC
(in planning) - Based on the encouraging results of the SAVOIR and
CALYPSO studies, we intend to initiate a global Phase III,
open-label, randomized, controlled study of ORPATHYS(R) plus
IMFINZI(R) versus sunitinib monotherapy versus IMFINZI(R)
monotherapy in patients with MET-driven, unresectable and locally
advanced or metastatic PRCC.
ORPATHYS(R) development in other cancer indications
ORPATHYS(R) opportunities are also continuing to be explored in
multiple other MET-driven tumor settings via investigator-initiated
studies including non-small cell lung cancer, gastric cancer and
colorectal cancer.
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. A dedicated organization of over 1,300
personnel 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 ORPATHYS(R) for the treatment of patients with gastric
cancer, the further clinical development of ORPATHYS(R) in this and
other indications, its expectations as to whether clinical studies
of ORPATHYS(R) 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 ORPATHYS(R) for
the treatment of patients with gastric cancer in China, its
potential to gain expeditious approvals for ORPATHYS(R) in other
jurisdictions such as the U.S., E.U. or Japan, the safety profile
of ORPATHYS(R) , the potential for ORPATHYS(R) to become a new
standard of care for gastric cancer patients, its ability to
implement and complete its further clinical development plans for
ORPATHYS(R) , its potential commercial launch of ORPATHYS(R) in
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(R) and IMFINZI(R) as combination therapeutics with
ORPATHYS(R) , such risks and uncertainties include assumptions
regarding the safety, efficacy, supply and continued regulatory
approval of TAGRISSO(R) and IMFINZI(R) . 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, +1 (917) 570 7340 (Mobile)
Solebury Trout bmiles@troutgroup.com
Europe - Ben Atwell / Alex Shaw, +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile)
FTI Consulting HUTCHMED@fticonsulting.com
Asia - Zhou Yi, +852 97 83 6894 (Mobile)
Brunswick HUTCHMED@brunswickgroup.com
Nominated Advisor
Atholl Tweedie / Freddy Crossley,
Panmure Gordon (UK) Limited +44 (20) 7886 2500
[1] Catenacci DV, Ang A, Liao WL, et al. MET tyrosine kinase
receptor expression and amplification as prognostic biomarkers of
survival in gastroesophageal adenocarcinoma. Cancer.
2017;123(6):1061-1070. doi:10.1002/cncr.30437
[2] Lee J, Kim ST, Kim K, et al. Tumor Genomic Profiling Guides
Patients with Metastatic Gastric Cancer to Targeted Treatment: The
VIKTORY Umbrella Trial. Cancer Discov. 2019;9(10):1388-1405.
doi:10.1158/2159-8290.CD-19-044
[3] Van Cutsem E, Karaszewska B, Kang YK, et al. A Multicenter
Phase II Study of AMG 337 in Patients with MET-Amplified
Gastric/Gastroesophageal Junction/Esophageal Adenocarcinoma and
Other MET-Amplified Solid Tumors. Clin Cancer Res.
2019;25(8):2414-2423. doi:10.1158/1078-0432.CCR-18-1337
[4] Global Cancer Observatory. China Fact Sheet.
gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf.
[5] Lu S, et al. Once-daily savolitinib in Chinese patients with
pulmonary sarcomatoid carcinomas and other non-small-cell lung
cancers harbouring MET exon 14 skipping alterations: a multicentre,
single-arm, open-label, phase 2 study. Lancet Respir Med. 2021 Jun
21:S2213-2600(21)00084-9. doi: 10.1016/S2213-2600(21)00084-9.
[6] Choueiri TK, et al. Efficacy of Savolitinib vs Sunitinib in
Patients With MET-Driven Papillary Renal Cell Carcinoma: The SAVOIR
Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Aug
1;6(8):1247-1255. doi: 10.1001/jamaoncol.2020.2218.
[7] Powles T, et al. A phase II study investigating the safety
and efficacy of savolitinib and durvalumab in metastatic papillary
renal cancer (CALYPSO). J Clin Oncol 37, 2019 (suppl 7S; abstr
545). doi: 10.1200/JCO.2019.37.7_suppl.545.
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