TIDMHCM
Hutchmed (China) Limited
01 November 2021
Press Release
HUTCHMED and AstraZeneca Initiate SAMETA Global Phase III Trial
of Savolitinib in Combination with PD-L1 Inhibitor IMFINZI(R) in
Patients with MET-Driven Advanced Papillary Renal Cell
Carcinoma
- Follows multiple global studies of savolitinib in papillary
renal cell carcinoma patients including SAVOIR and CALYPSO -
- In CALYPSO, savolitinib and IMFINZI(R) combination
demonstrated a 57% confirmed response rate in PRCC patients with
tumors harboring MET-driven alterations -
Hong Kong, Shanghai & Florham Park, NJ - Monday, November 1,
2021: HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM;
HKEX:13) and AstraZeneca PLC ("AstraZeneca") (LSE/STO/Nasdaq: AZN)
have initiated SAMETA, a global Phase III study of savolitinib
(ORPATHYS(R) in China), an oral, potent, and highly selective small
molecule inhibitor of MET, a receptor tyrosine kinase, in
combination with AstraZeneca's PD-L1 inhibitor IMFINZI(R)
(durvalumab) in patients with MET-driven advanced papillary renal
cell carcinoma ("PRCC"). The first patient received their first
dose on October 28, 2021.
The Phase III trial is an open-label, randomized, controlled
study in treatment-naïve patients with MET-driven, unresectable and
locally advanced or metastatic PRCC, to evaluate the efficacy and
safety of savolitinib in combination with IMFINZI(R) , compared to
single agent IMFINZI(R) or single agent SUTENT(R) (sunitinib), an
oral multi-kinase inhibitor considered the standard-of-care
treatment option in PRCC. The primary endpoint of the study is
median progression free survival ("PFS"). Other endpoints include
median overall survival ("OS"), objective response rate ("ORR"),
duration of response ("DoR"), 6-months and 12-months disease
control rate ("DCR"), time to second progression (PFS2), safety,
pharmacokinetics ("PK") and quality of life. Additional details may
be found at clinicaltrials.gov, using identifier NCT05043090.
About PRCC
PRCC is a subtype of kidney cancer that is unusually difficult
to treat, with low response rates from current treatment options
and no treatments approved for patients with tumors that harbor
MET-driven alterations. Worldwide, about 430,000 new patients were
diagnosed with kidney cancer in 2020.(1) In the US, an estimated
76,000 people will be diagnosed with kidney cancer in 2021(2) .
Approximately 90% of kidney tumors are renal cell carcinoma
("RCC"), which consist of several heterogeneous subtypes with
highly variable clinical courses and outcomes(3,4) . PRCC accounts
for up to 15% of RCC(4,5) . The MET gene has been found to be a
major chromosome-level alteration in 81% of type-1 PRCC and 46% of
type-2 PRCC, or 63% of PRCC(6) .
About Savolitinib (ORPATHYS(R) in China)
Savolitinib 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.
Savolitinib is marketed in China under the brand name
ORPATHYS(R) 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 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 Medicine (7) . 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(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 (8) and final analysis was presented
at the World Conference on Lung Cancer(9) . 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 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.
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 ) - 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 ) - 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 PRCC ( 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 Oncology (10) . 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(R) 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(R) , a PD-L1 antibody owned
by AstraZeneca. The study is evaluating the safety and efficacy of
the savolitinib/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 (11) , 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(R) PD-L1
inhibitor in MET-driven, unresectable and locally advanced or
metastatic PRCC ( 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(R) versus sunitinib monotherapy versus
IMFINZI(R) 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 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.(12) 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 IMFINZI(R)
IMFINZI (R) (durvalumab) is a human monoclonal antibody that
binds to the PD-L1 protein and blocks the interaction of PD-L1 with
PD-1 and CD80 proteins, countering the tumor's immune-evading
tactics and releasing the inhibition of immune responses.
IMFINZI (R) is the only approved immunotherapy in the
curative-intent setting of unresectable, Stage III NSCLC in
patients whose disease has not progressed after chemoradiation
therapy and is the global standard of care in this setting based on
the PACIFIC Phase III trial.
IMFINZI (R) is also approved in the US, EU, Japan, China and
many other countries around the world for the treatment of
extensive-stage small cell lung cancer ("SCLC") based on the
CASPIAN Phase III trial.
IMFINZI (R) is also approved for previously treated patients
with advanced bladder cancer in several countries. Since the first
approval in May 2017, more than 100,000 patients have been treated
with IMFINZI (R) .
As part of a broad development program, IMFINZI (R) is being
tested as a single treatment and in combinations with other
anti-cancer treatments for patients with NSCLC, SCLC, bladder
cancer, liver cancer, biliary tract cancer, esophageal cancer,
gastric and gastroesophageal cancer, cervical cancer, ovarian
cancer, endometrial cancer, and other solid tumors.
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 kidney
cancer, 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 kidney cancer, its potential to gain
expeditious approvals for savolitinib in other jurisdictions such
as China E.U. or Japan, the safety profile of savolitinib the
potential for savolitinib to become a new standard of care for
kidney cancer 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) The Global Cancer Observatory, kidney cancer fact sheet.
https://gco.iarc.fr/today/data/factsheets/cancers/29-Kidney-fact-sheet.pdf.
Accessed August 16, 2021.
(2) SEER, Cancer Stat Facts: Kidney and Renal Pelvis Cancer.
https://seer.cancer.gov/statfacts/html/kidrp.html. Accessed August
16, 2021.
(3) American Cancer Society. What Is Kidney Cancer?
https://www.cancer.org/cancer/kidney-cancer/about/what-is-kidney-cancer.html.
Accessed August 16, 2021.
(4) Leibovich BC, Lohse CM, Crispen PL, et al. Histological
subtype is an independent predictor of outcome for patients with
renal cell carcinoma. J Urol. 2010;183(4):1309-1315. doi:
10.1016/j.juro.2009.12.035.
(5)
https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-kidney-tumors/papillary-renal-cell-carcinoma.
Accessed August 16, 2021.
(6) Cancer Genome Atlas Research Network, Linehan WM, Spellman
PT, et al. Comprehensive Molecular Characterization of Papillary
Renal-Cell Carcinoma. N Engl J Med. 2016;374(2):135-145. doi:
10.1056/NEJMoa1505917.
(7) 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.
(8) 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.
(9) 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.
(10) 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.
(11) 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.
(12) 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.
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