RCS - Hutchmed China Ltd - HUTCHMED and AZ Initiate SACHI Phase 3 Trial

HUTCHMED (China)Announcement

24/11/2021 07:00

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RNS Number : 3210T  Hutchmed (China) Limited  24 November 2021

Press Release

 

HUTCHMED and AstraZeneca Initiate SACHI Phase III Trial of ORPATHYS(®) and TAGRISSO(®) Combination in Certain Lung Cancer Patients in China After Progression on EGFR Inhibitor Therapy

 

- Follows important findings from the TATTON 1  (#_edn1) study of the
combination in EGFR inhibitor refractory lung cancer patients whose tumors
harbor aberrations of MET -

Hong Kong, Shanghai & Florham Park, NJ - Wednesday, November 24, 2021:
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 NCT
(https://clinicaltrials.gov/ct2/show/NCT05015608) 05015608
(https://clinicaltrials.gov/ct2/show/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  (#_edn2)  More than a
third of the world's lung cancer patients are in China. 3  (#_edn3) Lung
cancer is broadly split into NSCLC and small cell lung cancer, with 80-85%
classified as NSCLC. 4  (#_edn4) The majority of NSCLC patients are diagnosed
with advanced disease while approximately 25-30% present with
resectable disease at diagnosis. 5  (#_edn5) (,) 6  (#_edn6) For patients
with resectable tumors, the majority of patients eventually develop recurrence
despite complete tumor resection and adjuvant chemotherapy. 7  (#_edn7)

 

Approximately 10-25% of NSCLC patients in the US and Europe, and 30-40% of
patients in Asia have EGFR-mutated NSCLC. 8  (#_edn8) (,) 9  (#_edn9) , 10 
(#_edn10) 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  (#_edn11)

 

MET is a tyrosine kinase receptor. 12  (#_edn12) 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  (#_edn13) (,) 14  (#_edn14)

 

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
(https://www.hutch-med.com/first-commercial-sale-of-orpathys-milestone-payment/)
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 (https://clinicaltrials.gov/ct2/show/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 15  (#_edn15) . 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 (https://clinicaltrials.gov/ct2/show/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
(https://clinicaltrials.gov/ct2/show/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  (#_edn16) ) and final analysis was presented
at the World Conference on Lung Cancer(1). 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 (https://clinicaltrials.gov/ct2/show/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 (https://clinicaltrials.gov/ct2/show/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 (https://clinicaltrials.gov/ct2/show/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
(https://clinicaltrials.gov/ct2/show/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( 17  (#_edn17) ).
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
(https://clinicaltrials.gov/ct2/show/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 Meeting( 18  (#_edn18) ), 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 (https://clinicaltrials.gov/ct2/show/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
(https://clinicaltrials.gov/ct2/show/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 
(#_edn19) 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 (https://www.hutch-med.com/) or
follow us on LinkedIn (https://www.linkedin.com/company/hutchmed/) .

 

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,             +1 (917) 570 7340 (Mobile)

Solebury Trout
bmiles@troutgroup.com (mailto:bmiles@troutgroup.com)
 Europe - Ben Atwell / Alex Shaw,   +44 20 3727 1030 / +44 7771 913 902 (Mobile) /

FTI Consulting                    +44 7779 545 055 (Mobile)

HUTCHMED@fticonsulting.com (mailto:HUTCHMED@fticonsulting.com)
 Asia - Zhou Yi,                    +852 9783 6894 (Mobile)

Brunswick
HUTCHMED@brunswickgroup.com (mailto:HUTCHMED@brunswickgroup.com)

 Nominated Advisor
 Atholl Tweedie / Freddy Crossley,  +44 (20) 7886 2500

Panmure Gordon (UK) Limited

 

 

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