RCS - Hutchmed China Ltd - Results of SAVANNAH Global Phase II Trial at WCLC

HUTCHMED (China)Announcement

13/07/2022 07:00

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RNS Number : 1941S  Hutchmed (China) Limited  13 July 2022

 

Press Release

 

HUTCHMED Highlights First Presentation of Results of the SAVANNAH Global Phase II Trial of Savolitinib plus TAGRISSO(®) at the 2022 WCLC Annual Meeting

 

- 49% ORR amongst SAVANNAH patients with higher MET levels -

 

Hong Kong, Shanghai & Florham Park, NJ - Wednesday, July 13, 2022:
HUTCHMED (China) Limited ("HUTCHMED (https://www.hutch-med.com/) ")
(Nasdaq/AIM:HCM; HKEX:13) today announces the first presentation of results
from the ongoing SAVANNAH global Phase II trial at the upcoming International
Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung
Cancer ("WCLC"), taking place August 6-9 in Vienna, Austria.

 

SAVANNAH is a global Phase II study of HUTCHMED and AstraZeneca's
(LSE/STO/Nasdaq:AZN) savolitinib in combination with AstraZeneca's
TAGRISSO(®) (osimertinib) in epidermal growth factor receptor
("EGFR")-mutated non-small cell lung cancer ("NSCLC") patients with
mesenchymal epithelial transition receptor ("MET") driven tumors, following
disease progression on treatment with TAGRISSO(®). In addition to continuing
TAGRISSO(®) treatment, patients received savolitinib 300mg once daily, 300mg
twice daily, or 600mg once daily. A total of 294 patients are enrolled in the
study.

 

The abstract presents results from an analysis of 193 efficacy evaluable
patients who received savolitinib 300mg once daily plus TAGRISSO(®) 80mg once
daily at data cut-off date of August 27, 2021. Qualifying MET aberrations are
MET amplification as detected by FISH (MET copy number ≥ 5 and/or MET: CEP
signal ratio ≥ 2  FISH5+ ) or MET overexpression as detected by IHC (3+ in
≥ 50% tumor cells  IHC50+ ). Additional analysis using an exploratory,
higher cut-off level of MET aberration are presented. The higher cut-off
levels for MET aberration are MET copy number ≥ 10 (FISH10+) and/or 3+
staining ≥ 90% tumor cells (IHC90+). The prevalence of this higher cut-off
levels of MET aberration was 34% of patients centrally tested for enrollment
in this study.

 

Results showed a trend toward improved response rates with increasing level of
MET aberration. Across all patients in this analysis, objective response rate
("ORR") was 32% [95% confidence interval ("CI"): 26-39%], median duration of
response ("DoR") was 8.3 months [95% CI: 6.9-9.7 months], and median
progression-free survival ("PFS") was 5.3 months [95% CI: 4.2- 5.8 months].
These results are consistent with the previously presented results from the
TATTON global exploratory study in over 220 EGFR mutation positive NSCLC
patients with MET amplified tumors following progression after treatment with
any EGFR TKI.

 

Among the SAVANNAH patients who met the criteria for higher cut-off levels of
MET aberration (n=108), ORR was 49% [95% CI: 39-59%], median DoR was 9.3
months [95% CI: 7.6-10.6 months], and mPFS was 7.1 months [95% CI: 5.3-8.0
months]. The safety profile of savolitinib plus TAGRISSO(®) was consistent
with the known profiles of the combination and each treatment alone.

 

Findings based on the ongoing SAVANNAH study, and the previously presented
TATTON Phase Ib/II study, supported the initiation of the SAFFRON global Phase
III study in patients with EGFR-mutated, MET-driven, locally advanced or
metastatic NSCLC whose disease progressed on first- or second-line treatment
with TAGRISSO(®) as the most recent therapy. Patients will be prospectively
selected for the higher level of MET aberration. The SAFFRON study will
evaluate the efficacy and safety of savolitinib in combination with
TAGRISSO(®) compared to pemetrexed plus platinum doublet-chemotherapy, the
current standard-of-care treatment in this setting. Approximately 324 patients
are planned to be randomized. If successful, the multi-regional clinical trial
("MRCT") may support registration for this combination globally. Two
registrational studies are ongoing in China in EGFR mutation positive NSCLC
with MET aberrations: the SANOVO study in treatment naïve patients, and SACHI
study in patients whose disease progressed following treatment with any EGFR
tyrosine kinase inhibitor ("TKI").

 

Further details from SAVANNAH will be available at WCLC. Further details of
the savolitinib WCLC updates are as follows:

 

 Title:          MET Biomarker-based Preliminary Efficacy Analysis in SAVANNAH:
                 savolitinib+osimertinib in EGFRm NSCLC Post-Osimertinib
 Presenter:      Myung-Ju Ahn, Division of Hematology-Oncology, Department of Medicine, Samsung
                 Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
 Other Authors:  Filippo De Marinis, Laura Bonanno, Byoung Chul Cho, Tae-Min Kim, Susanna
                 Cheng, Silvia Novello, Claudia Proto, Sang-We Kim, Jong Seok Lee, Giulio
                 Metro, James Chih-Hsin Yang, Wanning Xu, Ryan Hartmaier, Aino
                 Telaranta-Keerie, Lynne Poole, Lecia Sequist
 Session:        EP08.02 - Metastatic Non-small Cell Lung Cancer - Molecular Targeted
                 Treatments
 Abstract No.:   EP08.02-140
                 (https://library.iaslc.org/conference-program?product_id=25&author=&category=&date=&session_type=&session=&presentation=EP08.02-140&keyword=&cme=undefined&)

 

 Title:          SAFFRON: Ph3 Savolitinib + Osimertinib vs Chemotherapy in EGFRm NSCLC with MET
                 Overexpression/Amplification Post-Osimertinib
 Presenter:      Shun Lu, Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong
                 University, Shanghai, China
 Other Authors:  Wanning Xu, Aino Telaranta-Keerie, Nan Jia, Ryan Hartmaier
 Session:        EP08.02 - Metastatic Non-small Cell Lung Cancer - Molecular Targeted
                 Treatments
 Abstract No.:   EP08.02-138
                 (https://library.iaslc.org/conference-program?product_id=25&author=&category=&date=&session_type=&session=&presentation=EP08.02-138&keyword=&cme=undefined&)

 

 Title:          SANOVO: A Phase 3 Study of Savolitinib or Placebo in Combination with
                 Osimertinib in Patients with EGFR-mutant and MET Overexpressed NSCLC
 Presenter:      Qing Zhou, Guangdong General Hospital
 Other Authors:  Jingchang Li, Jianghong Wang, Lin Yang, Jian Fang, Xiaorong Dong, Tienan Yi,
                 Xuhong Min, Fei Xu, Jianhua Chen, Diansheng Zhong, Jun Bai, Laiyu Liu, Aiping
                 Zeng, Junfang Tang, Hongcheng Wu, Xian Luo, Jie Yu, Weiguo Su, Yi-Long Wu
 Session:        EP08.02 - Metastatic Non-small Cell Lung Cancer - Molecular Targeted
                 Treatments
 Abstract No.:   EP08.02-063
                 (https://library.iaslc.org/conference-program?product_id=25&author=&category=&date=&session_type=&session=&presentation=EP08.02-063&keyword=&cme=undefined&)

 

 

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  (#_edn1) More than a
third of the world's lung cancer patients are in China. 2  (#_edn2) Lung
cancer is broadly split into NSCLC and small cell lung cancer, with 80-85%
classified as NSCLC. 3  (#_edn3) The majority of NSCLC patients are diagnosed
with advanced disease while approximately 25-30% present with resectable
disease at diagnosis. 4  (#_edn4) (, 5  (#_edn5) )

 

Approximately 10-25% of NSCLC patients in the U.S. and Europe and 30-40% of
patients in Asia have EGFR-mutated NSCLC. 6  (#_edn6) (, 7  (#_edn7) , 8 
(#_edn8) ) These patients are particularly sensitive to treatment with an EGFR
TKI which blocks the cell-signaling pathways that drive the growth of tumor
cells. 9  (#_edn9) While an EGFR TKI can provide a durable survival benefit to
most patients, the majority will ultimately develop resistance to their
first-line treatment, underscoring a great unmet need to tackle acquired
resistance in this patient population. 10  (#_edn10)

 

MET is a tyrosine kinase receptor. 11  (#_edn11) 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  (#_edn12) (, 13  (#_edn13) )
Approximately 2-3% of NSCLC patients have tumors with MET exon 14 skipping
alterations, a targetable mutation in the MET gene. 14  (#_edn14) Among
patients who experience disease progression post-osimertinib treatment,
approximately 15-50% present with MET aberration. 15  (#_edn15) (, 16 
(#_edn16) , 17  (#_edn17) , 18  (#_edn18) , 19  (#_edn19) ) The prevalence of
MET amplification and overexpression may differ depending on the sample type,
detection method and assay cut-off used.

 

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 and collaboration
agreement to jointly develop and commercialize savolitinib. 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 (https://clinicaltrials.gov/ct2/show/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 20  (#_edn20) . 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. 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
(https://clinicaltrials.gov/ct2/show/NCT04923945) ).

 

Based on results of the TATTON and SAVANNAH studies below, several Phase III
studies of savolitinib in combination with TAGRISSO(®) have been initiated,
including SACHI, SANOVO and SAFFRON.

 

·      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) ) - Initiated in the second
half of 2021, this is a randomized, open-label study in China in EGFR mutated
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) ) - Initiated in the second
half of 2021, this is a randomized, double-blinded study in China in
untreated, unresectable or metastatic patients with EGFR mutated NSCLC with
MET overexpressed tumors.

 

·      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 an open-label,
global study in EGFR mutated NSCLC patients with MET amplified/overexpressed
tumors following progression after treatment with TAGRISSO(®). Results were
accepted for presentation at the upcoming WCLC annual meeting.

 

·      SAFFRON Phase III study of savolitinib in combination with
TAGRISSO(®) in patients who have progressed following TAGRISSO(®) due to MET
amplification or overexpression (NCT05261399
(https://clinicaltrials.gov/ct2/show/NCT05261399) ) - This is a global Phase
III study in patients with EGFR mutated, MET-driven, locally advanced or
metastatic NSCLC whose disease progressed on first- or second-line treatment
with TAGRISSO(®) as the most recent therapy.  Patients will be prospectively
selected for the higher level of MET aberration. The SAFFRON study will
evaluate the efficacy and safety of savolitinib in combination with
TAGRISSO(®) compared to pemetrexed plus platinum doublet-chemotherapy, the
current standard-of-care treatment in this setting. Approximately 324 patients
are planned to be randomized. If successful, the MRCT may support registration
for this combination globally.

 

·      TATTON Phase Ib/II 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 included over 220 EGFR mutated NSCLC patients with MET amplified tumors
following progression after treatment with any EGFR TKI. Results were
published in Lancet Oncology 21  (#_edn21) and final analysis was presented at
the 2021 World Conference on Lung Cancer 22  (#_edn22) . 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 first- and
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.

 

Savolitinib development in kidney cancer

SAMETA Phase III study in combination with IMFINZI(®) PD-L1 inhibitor in
MET-driven, unresectable and locally advanced or metastatic papillary renal
cell carcinoma ("RCC") (NCT05043090
(https://clinicaltrials.gov/ct2/show/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(® )versus sunitinib
monotherapy versus IMFINZI(®) monotherapy in patients with MET-driven,
unresectable and locally advanced or metastatic papillary RCC.

 

SAVOIR randomized, controlled study of savolitinib monotherapy in MET-driven
locally advanced or metastatic PRCC (NCT03091192
(https://clinicaltrials.gov/ct2/show/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 American Society
of Clinical Oncology ("ASCO") 2020 Program and published simultaneously in
JAMA Oncology 23  (#_edn23) . 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 the
median not reached at data cut-off.

 

CALYPSO study of savolitinib in combination with IMFINZI(®) PD-L1 inhibitor
in RCC (NCT02819596 (https://clinicaltrials.gov/ct2/show/NCT02819596) ) -
This investigator initiated open-label Phase I/II study of savolitinib in
combination with IMFINZI(®), a PD-L1 antibody owned by AstraZeneca, evaluated
the safety and efficacy of the savolitinib/IMFINZI(®) combination in
patients with RCC. An analysis of 41 papillary RCC patients was presented at
the 2021 ASCO Annual Meeting 24  (#_edn24) , 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
(https://clinicaltrials.gov/ct2/show/NCT04923932) ) - This is an open-label,
two-cohort, multi-center study to evaluate the efficacy, safety and
pharmacokinetics 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 25 
(#_edn25) . 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 4,900
personnel across all its companies, at the center of which is a team of over
1,800 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 (http://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
HUTCHMED's data to support New Drug Application approval of savolitinib for
the treatment of patients with NSCLC in China, the U.S., E.U., Japan or other
jurisdictions, the safety profile of savolitinib, the potential for
savolitinib to become a new standard of care for patients with NSCLC and other
types of cancer, its ability to implement and complete its further clinical
development plans for savolitinib, the potential commercial launch of
savolitinib 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
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 Nominated Advisor
 Atholl Tweedie / Freddy Crossley,  +44 (20) 7886 2500

Panmure Gordon (UK) Limited

 

 

 

 

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