RCS - Hutchmed China Ltd - Phase II/III Study of Fruquintinib and Sintilimab

HUTCHMED (China)Announcement

19/03/2025 07:15

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RNS Number : 2008B  Hutchmed (China) Limited  19 March 2025

Press Release

 

HUTCHMED and Innovent Jointly Announce that the FRUSICA-2 Phase II/III Study of Fruquintinib and Sintilimab Combination Has Met its Primary Endpoint in Advanced Renal Cell Carcinoma in China

 

Hong Kong, Shanghai & Florham Park, NJ - Wednesday, March 19, 2025:
HUTCHMED (China) Limited ("HUTCHMED (https://www.hutch-med.com/) ")
(Nasdaq/AIM:HCM; HKEX:13) and Innovent Biologics, Inc. ("Innovent") (HKEX:
01801), today jointly announce that the FRUSICA-2 Phase II/III clinical trial
evaluating fruquintinib in combination with sintilimab as second-line
treatment for locally advanced or metastatic renal cell carcinoma ("RCC") in
China has met its primary endpoint of progression free survival ("PFS") per
RECIST 1.1 as assessed by blinded independent central review (BICR).

 

The combination of fruquintinib and sintilimab received conditional approval
from the China National Medical Products Administration ("NMPA") for the
treatment of patients with advanced endometrial cancer with Mismatch Repair
proficient (pMMR) tumors that have failed prior systemic therapy and are not
candidates for curative surgery or radiation, based on data from the FRUSICA-1
study (NCT03903705 (https://www.clinicaltrials.gov/study/NCT03903705) ).

 

The FRUSICA-2 study is a randomized, open-label, active-controlled study to
evaluate the efficacy and safety of fruquintinib in combination with
sintilimab versus axitinib or everolimus monotherapy for the second-line
treatment of advanced RCC (NCT05522231
(https://clinicaltrials.gov/study/NCT05522231) ). In addition to the primary
endpoint PFS, the combination also demonstrated improvements in secondary
endpoints including objective response rate ("ORR") and duration of response
("DoR"). Full results will be submitted for presentation at an upcoming
scientific conference.

 

Prof Dingwei Ye of Fudan University Shanghai Cancer Center and the co-leading
Principal Investigator of the FRUSICA-2 study, said, "The rapid advancements
in targeted therapies, immunotherapies, and their combination regimens have
led to a significant evolution in the treatment landscape for advanced renal
cell carcinoma. Targeted therapy remains an indispensable and crucial
component in systemic treatment of advanced RCC in China. Optimizing the
selection of targeted therapy, either as monotherapy or in combination with
immunotherapy, for individual patients is a key focus of clinical interest.
The results from the FRUSICA‑2 study underscore the potential of the
fruquintinib and sintilimab combination to address the pressing medical needs
of patients with this challenging disease."

 

Prof Zhisong He of Peking University First Hospital and the co-leading
Principal Investigator of the FRUSICA-2 study, said, "The positive results
from this Phase III study of the fruquintinib and sintilimab combination
represent a significant advancement in the treatment of advanced renal cell
carcinoma. We are optimistic about the clinical implications of the findings
as we strive to provide more effective treatment options for patients who may
not have had adequate responses to previous therapies."

 

"The encouraging results from our study provide clear evidence for the
combination of fruquintinib and sintilimab as a viable new treatment option
for advanced renal cell carcinoma patients who have progressed on previous
therapy. This not only reaffirms our commitment to advancing cancer therapies
but also represents an important step forward in addressing unmet medical
needs within this patient population," said Dr Michael Shi, Head of R&D
and Chief Medical Officer of HUTCHMED. "I extend my heartfelt gratitude to the
patients and investigators who participated in this research; their
contributions have been vital to our success. We look forward to sharing
detailed findings with regulatory authorities and progressing toward NDA
filings in the coming months."

 

"We are encouraged by the positive results in the FRUSICA-2 clinical trial.
These outcomes not only underscore the great potential of the combination
therapy of sintilimab and fruquintinib but also bring new hope to
previously-treated patients with advanced renal cell carcinoma. We look
forward to working closely with HUTCHMED to jointly advance the registrational
communication of this innovative combo therapy and make it available to
patients as soon as possible," said Dr Hui Zhou, Senior Vice President of
Innovent.

 

About Kidney Cancer and RCC

It is estimated that approximately 435,000 new patients were diagnosed with
kidney cancer worldwide in 2022.(( 1  (#_edn1) )) In China, an estimated
74,000 new patients were diagnosed with kidney cancer in 2022.(( 2  (#_edn2)
)) Approximately 90% of kidney tumors are RCC.

 

About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three vascular endothelial
growth factor ("VEGF") receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a
pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to
have enhanced selectivity that limits off-target kinase activity, allowing for
drug exposure that achieves sustained target inhibition and flexibility for
potential use as part of a combination therapy. 3  (#_edn3)

 

About Fruquintinib Approvals

Fruquintinib is co-developed and co-marketed in China by HUTCHMED and Eli
Lilly and Company under the brand name ELUNATE(®). It is approved for the
treatment of patients with metastatic colorectal cancer who have previously
received fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy, and
those who have previously received or are not suitable for receiving anti-VEGF
therapy or anti-epidermal growth factor receptor (EGFR) therapy (RAS
wild-type) in China. It was included in the China National Reimbursement Drug
List (NRDL) in January 2020. Since its launch in China, over 100,000 patients
with colorectal cancer have been treated with fruquintinib.

 

The combination of ELUNATE(®) (fruquintinib) and TYVYT(®) (sintilimab
injection) has conditional approval in China for the treatment of patients
with advanced endometrial cancer with Mismatch Repair proficient (pMMR) tumors
that have failed prior systemic therapy and are not candidates for curative
surgery or radiation.

 

Takeda holds the exclusive worldwide license to further develop,
commercialize, and manufacture fruquintinib outside mainland China, Hong Kong
and Macau, marketing it under the brand name FRUZAQLA(®). Fruquintinib
received approval for the treatment of previously treated metastatic
colorectal cancer in the US
(https://www.hutch-med.com/us-fda-approval-of-fruzaqla-fruquintinib/) in
November 2023, in the EU
(https://www.hutch-med.com/european-commission-approval-for-fruzaqla-fruquintinib/)
in June 2024, in Switzerland and Argentina in August 2024, in Canada, Japan
(https://www.hutch-med.com/japan-approval-for-fruzaqla-fruquintinib/) and the
United Kingdom in September 2024, in Australia and Singapore in October 2024
and in Israel and the United Arab Emirates in December 2024. Regulatory
applications are progressing in many other jurisdictions.

 

The global regulatory submissions are based on data from two large,
randomized, controlled Phase III trials in colorectal cancer, the global,
multi-regional FRESCO-2 trial and the FRESCO trial conducted in China, showing
consistent benefit among a total of 734 metastatic colorectal cancer patients
treated with fruquintinib. Safety profiles were consistent across trials.
Results from the FRESCO-2 trial were published
(https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00772-9/fulltext)
in The Lancet in June 2023, 4  (#_edn4) while results from the FRESCO trial
were published (https://jamanetwork.com/journals/jama/fullarticle/2685988) in
The Journal of the American Medical Association, JAMA. 5  (#_edn5)

 

 

The safety and efficacy of fruquintinib for the following investigational uses
have not been established and there is no guarantee that it will receive
health authority approval or become commercially available in any country for
the uses being investigated:

About Fruquintinib for Second-line Treatment of RCC

The U.S. Food and Drug Administration (FDA) has approved five immune-oncology
combination therapies for the first-line treatment of advanced RCC. However,
only one immune-oncology combination therapy has been approved in China for
advanced RCC patients classified as having intermediate or poor risk by the
International mRCC Database Consortium (IMDC). Single-agent targeted therapy
continues to be one of the primary choices for first-line treatment of
advanced RCC in China. Notably, advanced RCC patients who have experienced
failure with single-agent targeted therapy previously still indicate an unmet
medical need.

 

Results from a proof-of-concept Phase Ib/II study of fruquintinib plus
sintilimab were published in Targeted Oncology in January 2025. The
combination demonstrated promising efficacy and a tolerable safety profile in
this setting. At the data cutoff of October 9, 2024, all 20 enrolled
previously treated patients were evaluable for efficacy, with a median
follow-up duration of 45.7 months. The confirmed ORR was 60.0% and DCR was
85.0%. Median DoR was 13.9 months and median PFS was 15.9 months. Overall
survival ("OS") was not reached, and the 36-month OS rate was 58.3%. 6 
(#_edn6)

 

About Sintilimab

Sintilimab, marketed as TYVYT(®) (sintilimab injection) in China, is a PD-1
immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly
and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody,
which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 /
PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells.  7 
(#_edn7)

 

In China, sintilimab has been approved and included in the updated NRDL for
seven indications. The updated NRDL reimbursement scope for TYVYT(®)
(sintilimab injection) includes:

·      For the treatment of relapsed or refractory classic Hodgkin's
lymphoma after two lines or later of systemic chemotherapy;

·      For the first-line treatment of unresectable locally advanced or
metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver
gene mutations;

·      For the treatment of patients with EGFR-mutated locally advanced
or metastatic non-squamous non-small cell lung cancer who progressed after
EGFR-TKI therapy;

·      For the first-line treatment of unresectable locally advanced or
metastatic squamous non-small cell lung cancer;

·      For the first-line treatment of unresectable or metastatic
hepatocellular carcinoma with no prior systematic treatment;

·      For the first-line treatment of unresectable locally advanced,
recurrent or metastatic esophageal squamous cell carcinoma;

·      For the first-line treatment of unresectable locally advanced,
recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.

 

Furthermore, sintilimab's eighth indication, in combination with fruquintinib
for the treatment of patients with advanced endometrial cancer with pMMR
tumors that have failed prior systemic therapy and are not candidates for
curative surgery or radiation, was conditional approved by the NMPA in
December 2024. And the NDA for sintilimab in combination with ipilimumab as
neoadjuvant treatment for resectable MSI-H/dMMR colon cancer is under the NMPA
review and has been granted Priority Review designation.

 

In addition, three clinical studies of sintilimab have met their primary
endpoints:

·      Phase 2 study of sintilimab monotherapy as second-line treatment
of esophageal squamous cell carcinoma;

·      Phase 3 study of sintilimab monotherapy as second-line treatment
for squamous non-small cell lung cancer with disease progression following
platinum-based chemotherapy;

·      Phase 2/3 study of sintilimab in combination with fruquintinib
versus axitinib or everolimus monotherapy for the second-line treatment of
advanced RCC.

 

Statement: Innovent does not recommend the use of any unapproved
drug(s)/indication(s).

 

About HUTCHMED

HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage,
biopharmaceutical company. It is committed to the discovery, global
development and commercialization of targeted therapies and immunotherapies
for the treatment of cancer and immunological diseases. Since inception,
HUTCHMED has focused on bringing drug candidates from in-house discovery to
patients around the world, with its first three medicines marketed in China,
the first of which is also approved around the world including in the US,
Europe and Japan. 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/) .

 

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the
mission to empower patients worldwide with affordable, high-quality
biopharmaceuticals. The company discovers, develops, manufactures and
commercializes innovative medicines that target some of the most intractable
diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic,
autoimmune and eye diseases. Innovent has launched 15 products in the market.
It has 3 new drug applications under regulatory review, 3 assets in Phase III
or pivotal clinical trials and 16 more molecules in early clinical stage.
Innovent partners with over 30 global healthcare companies, including Lilly,
Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.

 

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent
maintains the highest standard of industry practices and works collaboratively
to advance the biopharmaceutical industry so that first-rate pharmaceutical
drugs can become widely accessible. For more information, visit
www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Statement:

（1）Innovent does not recommend the use of any unapproved drug
(s)/indication(s).

（2）Ramucirumab (Cyramza(®)) and Selpercatinib (Retsevmo(®)) and
Pirtobrutinib (Jaypirca(®)) were developed by Eli Lilly and Company.

 

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 the fruquintinib and sintilimab combination for the
treatment of patients with RCC and the further clinical development of the
fruquintinib and sintilimab combination in this and other indications.
Forward-looking statements involve risks and uncertainties. Such risks and
uncertainties include, among other things, assumptions regarding the timing
and outcome of clinical studies and the sufficiency of clinical data to
support NDA approval of the fruquintinib and sintilimab combination for the
treatment of patients with RCC or other indications in China or other
jurisdictions, its potential to gain approvals from regulatory authorities on
an expedited basis or at all, the safety profile of the fruquintinib and
sintilimab combination, HUTCHMED's ability to fund, implement and complete its
further clinical development and commercialization plans for fruquintinib and
the timing of these events. In addition, as certain studies rely on the use of
other drug products such as sintilimab as combination therapeutics with
fruquintinib, such risks and uncertainties include assumptions regarding the
safety, efficacy, supply and continued regulatory approval of these
therapeutics. 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 The Stock
Exchange of Hong Kong Limited and on AIM. 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.

Medical Information

This press release contains information about products that may not be
available in all countries, or may be available under different trademarks,
for different indications, in different dosages, or in different strengths.
Nothing contained herein should be considered a solicitation, promotion or
advertisement for any prescription drugs including the ones under development.

 

CONTACTS
 Investor Enquiries                                   +852 2121 8200 / ir@hutch-med.com (mailto:ir@hutch-med.com)

 Media Enquiries
 FTI Consulting -                                     +44 20 3727 1030 / HUTCHMED@fticonsulting.com
                                                      (mailto:HUTCHMED@fticonsulting.com)
 Ben Atwell / Alex Shaw                               +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile)
 Brunswick - Zhou Yi                                  +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com
                                                      (mailto:HUTCHMED@brunswickgroup.com)

 Panmure Liberum                                      Nominated Advisor and Joint Broker
 Atholl Tweedie / Freddy Crossley / Rupert Dearden    +44 20 7886 2500

 HSBC                                                 Joint Broker
 Simon Alexander / Alina Vaskina / Arnav Kapoor       +44 20 7991 8888

 Cavendish                                            Joint Broker
 Geoff Nash / Nigel Birks                             +44 20 7220 0500

 

 1  (#_ednref1)    The Global Cancer Observatory, kidney cancer fact sheet.
https://gco.iarc.who.int/media/globocan/factsheets/cancers/29-kidney-fact-sheet.pdf
(https://gco.iarc.who.int/media/globocan/factsheets/cancers/29-kidney-fact-sheet.pdf)
. Accessed February 19, 2025.

 2  (#_ednref2)    The Global Cancer Observatory, China fact sheet.
https://gco.iarc.who.int/media/globocan/factsheets/populations/160-china-fact-sheet.pdf
(https://gco.iarc.who.int/media/globocan/factsheets/populations/160-china-fact-sheet.pdf)
. Accessed February 19, 2025.

 3  (#_ednref3)    Sun Q, et al. Discovery of fruquintinib, a potent and
highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases
for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45. doi:
10.4161/15384047.2014.964087.

 4  (#_ednref4)     Dasari NA, et al. Fruquintinib versus placebo in
patients with refractory metastatic colorectal cancer (FRESCO‑2): an
international, multicentre, randomised, double‑blind, Phase III study.
Lancet. 2023;402(10395):41‑53. doi:10.1016/S0140‑6736(23)00772‑9.

 5  (#_ednref5)     Li J, et al. Effect of Fruquintinib vs Placebo on
Overall Survival in Patients With Previously Treated Metastatic Colorectal
Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486-2496.
doi:10.1001/jama.2018.7855.

 6  (#_ednref6)    Xu H, et al. Fruquintinib Plus Sintilimab in Patients
with Treatment‑Naïve and Previously Treated Advanced Renal Cell Carcinoma:
Results from a Phase Ib/II Clinical Trial. Targeted Oncology. 2025;
20:113-125. doi.org/10.1007/s11523-024-01120-6.

 7  (#_ednref7)    Wang J, et al. Durable blockade of PD-1 signaling links
preclinical efficacy of sintilimab to its clinical benefit. mAbs 2019;11(8):
1443-1451. doi: 10.1080/19420862.2019.1654303.

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