TIDMHCM
Hutchmed (China) Limited
07 March 2022
Press Release
HUTCHMED Receives a US$15 million Milestone from AstraZeneca for
Initiating Start-up Activities for a Global Phase III Study of
ORPATHYS(R) in Lung Cancer
Hong Kong, Shanghai & Florham Park, NJ - Monday, March 7,
2022: (" HUTCHMED ") (Nasdaq/AIM: HCM; HKEX: 13) today announces
that it has received a US$15 million milestone payment from
AstraZeneca PLC ("AstraZeneca") (LSE/STO/Nasdaq: AZN).
This milestone has been triggered by the initiation of start-up
activities for SAFFRON, the first global Phase III study for
ORPATHYS(R) in combination with TAGRISSO(R) in epidermal growth
factor receptor ("EGFR")-mutated non-small cell lung cancer
("NSCLC") patients with mesenchymal epithelial transition receptor
("MET") driven tumors following progression after TAGRISSO(R) .
SAFFRON, which is expected to commence enrolling patients in
mid-2022, follows important lessons learned from the SAVANNAH
study, which is targeted to be presented at an upcoming scientific
conference in the second half of 2022.
To date, AstraZeneca has now paid HUTCHMED US$85 million of the
total US$140 million in upfront payments, development and
first-sale milestones due under the license and collaboration
agreement between HUTCHMED and AstraZeneca.
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. [1]
More than a third of the world's lung cancer patients are in China.
[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 are diagnosed with advanced disease while approximately
25-30% present with resectable disease at diagnosis. [4](, [5]) For
patients with resectable tumors, the majority of patients
eventually develop recurrence despite complete tumor resection and
adjuvant chemotherapy. [6]
Approximately 10-25% of NSCLC patients in the U.S. and Europe,
and 30-40% of patients in Asia have EGFR-mutated NSCLC. [7](, [8] ,
[9]) These patients are particularly sensitive to treatment with an
EGFR tyrosine kinase inhibitor ("TKI") which blocks the
cell-signaling pathways that drive the growth of tumor cells.
[10]
MET is a tyrosine kinase receptor. [11] 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.
[12](, [13]) Approximately 2-3% of NSCLC patients have tumors with
MET exon 14 skipping alterations, a targetable mutation in the MET
gene. [14]
About Savolitinib (ORPATHYS(R) 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(R) 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 and
collaboration agreement to jointly develop and commercialize
savolitinib. Under the current terms of the agreement, a US$15
million milestone payment is triggered by the initiation of
start-up activities for the SAFFRON study. 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.
Savolitinib development in NSCLC
Phase II study of savolitinib monotherapy in MET Exon 14
skipping alteration NSCLC ( NCT02897479 ) - The conditional
approval in China for MET Exon 14 skipping alteration NSCLC was
based on the results of a Phase II study that were published in The
Lancet Respiratory Medicine [15] . At a median follow up of 17.6
months, savolitinib 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. Disease control rate ("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).
Based on results of the TATTON and SAVANNAH studies below,
several Phase III studies of savolitinib in combination with
TAGRISSO(R) have been initiated, including SACHI, and SANOVO and
SAFFRON.
SACHI Phase III study of savolitinib in combination with
TAGRISSO(R) in patients who have progressed following EGFR TKI
treatment due to MET amplification ( NCT05015608 ) - Initiated in
the second half of 2021, 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(R) in treatment-naïve patients with EGFR mutant positive
NSCLC with MET overexpression ( NCT05009836 ) - Initiated in the
second half of 2021, this is a randomized, blinded study in China
in untreated, unresectable or metastatic patients with EGFR
mutation positive NSCLC with MET positive tumors.
TATTON Phase Ib/II studies of savolitinib in combination with
TAGRISSO(R) 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 Oncology [16]
and final analysis was presented at the World Conference on Lung
Cancer [17] . 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 (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 EGFR mutated NSCLC
patients with MET amplified/overexpressed tumors following
progression after treatment with TAGRISSO(R) , an EGFR TKI owned by
AstraZeneca. We plan to submit results for presentation at an
upcoming scientific conference.
Savolitinib development in kidney cancer
SAMETA Phase III study in combination with IMFINZI(R) PD-L1
inhibitor in MET-driven, unresectable and locally advanced or
metastatic papillary renal cell carcinoma ("RCC") ( NCT05043090 ) -
Based on the encouraging results of the SAVOIR monotherapy and
CALYPSO combination therapy studies below, we initiated SAMETA, a
global Phase III, open-label, randomized, controlled study of
savolitinib plus IMFINZI(R) versus sunitinib monotherapy versus
IMFINZI(R) monotherapy in patients with MET-driven, unresectable
and locally advanced or metastatic papillary RCC.
SAVOIR randomized, controlled study of savolitinib monotherapy
in MET-driven PRCC ( NCT03091192 ) - 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 Oncology [18] .
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 study of savolitinib in combination with IMFINZI(R)
PD-L1 inhibitor in RCC ( NCT02819596 ) - This investigator
initiated open-label Phase I/II study of savolitinib in combination
with IMFINZI(R) , a PD-L1 antibody owned by AstraZeneca, evaluated
the safety and efficacy of the savolitinib/IMFINZI(R) combination
in patients with RCC. An analysis of 41 papillary RCC patients was
presented at the 2021 American Society of Clinical Oncology (ASCO)
Annual Meeting [19] , 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.
Savolitinib development in gastric cancer and other cancer
indications
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 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 [20] . 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 opportunities are also continuing to be explored in
multiple other MET-driven tumor settings via investigator-initiated
studies including 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. It has more than 4,600 personnel across all
its companies, at the center of which is a team of over 1,500 in
oncology/immunology. Since inception it has advanced 12 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(R) and IMFINZI(R) as combination therapeutics with
savolitinib, 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] World Health Organization. International Agency for Research
on Cancer. Lung Fact Sheet. Available at gco.iarc.fr/ today/ data/
factsheets/ cancers/ 15-Lung-fact-sheet.pdf. Accessed June
2021.
[2] World Health Organization. International Agency for Research
on Cancer. Globocan China Fact Sheet 2020. Available at
gco.iarc.fr/ today/ data/ factsheets/
populations/160-china-fact-sheets.pdf. Accessed June 2021.
[3] LUNGevity Foundation. Types of Lung Cancer. Available at lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed June 2021.
[4] Cagle PT, Allen TC, Olsen RJ. Lung Cancer Biomarkers:
Present Status and Future Developments. Arch Pathol Lab Med. 2013;
137(9): 1191-1198. doi: 10.5858/arpa.2013-0319-CR.
[5] Le Chevalier T, et al. Adjuvant Chemotherapy for Resectable
Non-Small Cell Lung Cancer: Where is it Going? Ann Oncol.
2010;21:vii196-vii198. doi: 10.1093/annonc/mdq376.
[6] Pignon J, et al. Lung Adjuvant Cisplatin Evaluation: A
Pooled Analysis by the LACE Collaborative Group. J Clin Oncol.
2008;26:3552-3559. doi: 10.1200/jco.2007.13.9030.
[7] Zhang YL, 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):78985-78993. doi:
10.18632/oncotarget.12587.
[8] Keedy V.L., 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. doi:
10.1200/JCO.2010.31.8923 .
[9] 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. doi:
10.1136/jclinpath-2012-201194.
[10] Cross DA, et al. AZD9291, an Irreversible EGFR TKI,
Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung
Cancer. Cancer Discov. 2014;4(9):1046-1061. doi:
10.1158/2159-8290.CD-14-0337.
[11] Organ SL, Tsao MS. An overview of the c-MET signaling
pathway. Ther Adv Med Oncol 2011; 3(1 Suppl):S7-S19. doi: 10.1177/
1758834011422556.
[12] Ramalingham SS, et al. Mechanisms of acquired resistance to
first-line osimertinib: Preliminary data from the phase III FLAURA
study. Ann Oncol. 2018; 29, SUPPLEMENT 8, VIII740. doi:
10.1093/annonc/mdy424.063.
[13] Sterlacci W, et al. MET overexpression and gene
amplification: prevalence, clinico-pathological characteristics and
prognostic signific-ance in a large cohort of patients with
surgically resected NSCLC. Virchows Arch. 2017;471(1):49-55.
doi:10.1007/s00428-017-2131-1.
[14] Vuong HG, et al. Clinicopathological implications of MET
exon 14 mutations in non-small cell lung cancer - A systematic
review and meta-analysis. Lung Cancer 2018; 123: 76-82. doi:
10.1016/j.lungcan.2018.07.006 .
[15] 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.
[16] Sequist LV, et al. Osimertinib plus savolitinib in patients
with EGFR mutation-positive, MET-amplified, non-small-cell lung
cancer after progression on EGFR tyrosine kinase inhibitors:
interim results from a multicentre, open-label, phase 1b study.
Lancet Oncol. 2020;21(3):373-386.
doi:10.1016/S1470-2045(19)30785-5.
[17] Han JY, et al. Osimertinib + savolitinib in patients with
EGFRm MET-amplified/overexpressed NSCLC: Phase Ib TATTON Parts B
and D final analysis. WCLC January 2021 #FP14.03. doi:
10.1016/j.jtho.2021.01.146.
[18] 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.
[19] Suarez C, et al. Clinical activity of durvalumab and
savolitinib in MET-driven, metastatic papillary renal cancer. J
Clin Oncol 39, no. 15_suppl (May 20, 2021) 4511-4511. doi:
10.1200/JCO.2021.39.15_suppl.4511.
[20] Lee J, 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-19-0442.
This information is provided by Reach, the non-regulatory press
release distribution service of RNS, part of the London Stock
Exchange. Terms and conditions relating to the use and distribution
of this information may apply. For further information, please
contact rns@lseg.com or visit www.rns.com.
Reach is a non-regulatory news service. By using this service an
issuer is confirming that the information contained within this
announcement is of a non-regulatory nature. Reach announcements are
identified with an orange label and the word "Reach" in the source
column of the News Explorer pages of London Stock Exchange's
website so that they are distinguished from the RNS UK regulatory
service. Other vendors subscribing for Reach press releases may use
a different method to distinguish Reach announcements from UK
regulatory news.
RNS may use your IP address to confirm compliance with the terms
and conditions, to analyse how you engage with the information
contained in this communication, and to share such analysis on an
anonymised basis with others as part of our commercial services.
For further information about how RNS and the London Stock Exchange
use the personal data you provide us, please see our Privacy
Policy.
NRAUPUBPWUPPUQM
(END) Dow Jones Newswires
March 07, 2022 02:01 ET (07:01 GMT)
Hutchison China Meditech (LSE:0J7G)
Graphique Historique de l'Action
De Juin 2024 à Juil 2024
Hutchison China Meditech (LSE:0J7G)
Graphique Historique de l'Action
De Juil 2023 à Juil 2024