RCS - Hutchmed China Ltd - Phase Ib/II Trial of Fruquintinib & Tislelizumab

HUTCHMED (China)Announcement

26/08/2021 07:00

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RNS Number : 7824J  Hutchmed (China) Limited  26 August 2021

Press Release

 

HUTCHMED Initiates a Phase Ib/II Trial of Fruquintinib in Combination with Tislelizumab in Advanced Triple Negative Breast Cancer or Advanced Endometrial Cancer

 

Hong Kong, Shanghai & Florham Park, NJ - Thursday, August 26, 2021:
HUTCHMED (China) Limited ("HUTCHMED (https://www.hutch-med.com/) ")
(Nasdaq/AIM: HCM; HKEX:13) has initiated a Phase Ib/II study of fruquintinib
in combination with BeiGene's tislelizumab in patients with advanced triple
negative breast cancer ("TNBC") or advanced endometrial cancer ("EC") in the
U.S. The first patient was dosed on August 24, 2021. This trial is to explore
the potential for the addition of a highly selective vascular endothelial
growth factor receptor ("VEGFR") inhibitor, fruquintinib, to anti-programmed
death-1 ("PD-1") antibody tislelizumab in inducing activity to immune
checkpoint inhibitors.

 

This is an open-label, multi-center, non-randomized study to assess the safety
and efficacy of fruquintinib in combination with tislelizumab in patients with
locally advanced or metastatic TNBC or advanced EC. This study will be
conducted in two parts; a safety lead-in phase (Part 1) and a dose expansion
phase (Part 2). The safety lead-in phase will determine safety and
tolerability and the recommended Phase II dose ("RP2D") of the combination. In
the dose expansion phase, the RP2D will be administered to two cohorts of
patients: Cohort A - Patients with TNBC who have received prior therapy with
an immune checkpoint inhibitor; and Cohort B - Patients with TNBC who have not
received prior therapy with an immune checkpoint inhibitor. A cohort
evaluating the combination in second line advanced EC is anticipated to open
in 3Q2021. Additional details may be found at clinicaltrials.gov, using
identifier NCT04577963 (https://clinicaltrials.gov/ct2/show/NCT04577963) .

 

 

About TNBC and EC

 

Breast cancer is a common type of cancer in the U.S., estimated to be
diagnosed in over 281,000 women during 2021. 1  TNBC is one of several
subtypes of breast cancer, accounting for approximately 10% of newly diagnosed
breast cancer cases. 2  The number of women living with TNBC in the U.S. was
estimated to be over 150,000 in 2018. 3  PD-L1 expression is estimated to be
present in approximately 20% of TNBC. 4   TNBC is distinguished from the
other subtypes of breast cancer in that the cancer cells do not have receptors
for the hormones estrogen or progesterone (hormone receptor negative) and do
not make excessive amount of the protein human epidermal growth factor
receptor 2 (HER2). TNBC is more aggressive and has a worse prognosis compared
to other types of breast cancer.

 

EC is the fourth most common type of cancer among women in the U.S., estimated
to be diagnosed in over 66,000 women during 2021. 5   The number of women
living with EC in the U.S. was estimated to be over 800,000 in 2018. Options
are limited beyond front line chemotherapy treatment for the 20-30% of women
who are diagnosed at an advanced stage of the disease, as well as those who
develop advanced disease that are not curable with surgery.  Among patients
with EC, an estimated 14% of advanced stage tumors express PD-L1, and
approximately 20-30% of EC are microsatellite instability-high
(MSI-H). 6 (, 7 , 8 , 9 )

 

Immune checkpoint inhibitors ("ICIs") have improved clinical outcomes in TNBC
and EC, but a large proportion of patients do not respond to ICIs and initial
responders eventually develop resistance. Combination therapy including VEGFR
inhibition may improve the clinical efficacy of ICIs by promoting inhibition
of angiogenesis in the tumor region, which can suppress tumor growth and
reduce metastasis.

 

 

About Fruquintinib

 

Fruquintinib is a highly selective and potent oral inhibitor of VEGFR-1, -2
and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis.
Fruquintinib was designed to improve kinase selectivity to minimize off-target
toxicities, improve tolerability and provide more consistent target coverage.
The generally good tolerability in patients to date, along with fruquintinib's
low potential for drug-drug interaction based on preclinical assessment,
suggests that it may also be highly suitable for combinations with other
anti-cancer therapies.

 

HUTCHMED retains all rights to fruquintinib outside of China. In China,
HUTCHMED is partnered with Eli Lilly and Company and is responsible for
development and execution of all on-the-ground medical detailing, promotion
and local and regional marketing.

 

 

About Fruquintinib Development

 

Metastatic colorectal cancer in China: Fruquintinib was approved for marketing
by the China National Medical Products Administration ("NMPA") in September
2018 and commercially launched in China in late November 2018 under the brand
name Elunate(®). It was included in the China National Reimbursement Drug
List (NRDL) in January 2020. Elunate(®) is for the treatment of patients with
metastatic colorectal cancer ("CRC") who have been previously treated with
fluoropyrimidine, oxaliplatin and irinotecan, including those who have
previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild
type). Results of the FRESCO study, a Phase III pivotal registration trial of
fruquintinib in 416 patients with metastatic CRC in China, were published
(https://jamanetwork.com/journals/jama/fullarticle/2685988) in The Journal of
the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov
identifier: NCT02314819 (https://clinicaltrials.gov/ct2/show/NCT02314819) ).

 

Metastatic CRC in the U.S., Europe, and Japan: The U.S. Food and Drug
Administration ("FDA") granted Fast Track Designation for the development of
fruquintinib for the treatment of patients with metastatic CRC in June 2020
(https://www.hutch-med.com/fruquintinib-granted-us-fda-fast-track-designation-for-mcrc/)
. A Phase III registration study of fruquintinib for the treatment of patients
with metastatic CRC, FRESCO-2, is currently underway in the U.S., Europe,
Japan and Australia. Additional details of the study may be found at
clinicaltrials.gov, using identifier NCT04322539
(https://clinicaltrials.gov/ct2/show/NCT04322539) . The U.S. FDA has
acknowledged that the totality of the fruquintinib clinical data, including
the FRESCO-2 study (if positive), the prior positive Phase III FRESCO study
demonstrating improvement in overall survival that led to fruquintinib
approval for metastatic CRC in China in 2018, and additional completed and
ongoing supporting studies in metastatic CRC, could potentially support a New
Drug Application (NDA) for the treatment of patients with advanced metastatic
CRC (third-line and above). The FRESCO-2 study design was also reviewed and
endorsed by The European Medicines Agency (EMA) and Japanese Pharmaceuticals
and Medical Devices Agency (PMDA).

 

Gastric Cancer in China: In October 2017, HUTCHMED initiated the FRUTIGA
study, a randomized, double-blind, Phase III trial evaluating the efficacy and
safety of fruquintinib combined with paclitaxel for second-line treatment of
advanced gastric or esophagogastric junction ("GEJ") adenocarcinoma. The trial
is designed to enroll patients who did not respond to first-line standard
chemotherapy. Subjects receive either fruquintinib combined with paclitaxel or
placebo combined with paclitaxel. Patients are randomized at a 1:1 ratio and
stratified according to factors such as stomach vs. GEJ tumor type and
performance status. The primary efficacy endpoint is overall survival.
Secondary efficacy endpoints include progression-free survival (as defined by
RECIST 1.1), objective response rate, disease control rate, duration of
response, and quality-of-life score (EORTC QLQ-C30, version 3.0). Biomarkers
related to the antitumor activity of fruquintinib will also be explored
(clinicaltrials.gov identifier: NCT03223376
(https://clinicaltrials.gov/ct2/show/NCT03223376) ). In June 2020, HUTCHMED
completed a planned interim data review. Based on the preset criteria, the
Independent Data Monitoring Committee (IDMC) recommended that the trial
continue.

 

Metastatic breast cancer: HUTCHMED initiated this open-label, multi-center,
non-randomized, Phase Ib/II study in the U.S. to assess the safety and
efficacy of fruquintinib in combination with tislelizumab in patients with
advanced, refractory TNBC. This study is being conducted to investigate if the
addition of fruquintinib can potentially induce activity to ICIs therapy in
TNBC. Additional details of the study may be found at clinicaltrials.gov,
using identifier NCT04577963 (https://clinicaltrials.gov/ct2/show/NCT04577963)
. Safety and preliminary efficacy of fruquintinib were demonstrated in
advanced solid tumors, including TNBC, in a phase I study conducted in China
(NCT01645215 (https://clinicaltrials.gov/ct2/show/NCT01645215) ) and a phase
1/1b study is ongoing in the United States (NCT03251378
(https://clinicaltrials.gov/ct2/show/NCT03251378) ).

 

Other Immunotherapy combinations: HUTCHMED has entered into other
collaboration agreements to evaluate the safety, tolerability and efficacy of
fruquintinib in combination with PD-1 monoclonal antibodies, including with
Tyvyt (https://www.hutch-med.com/a181129/) (®
(https://www.hutch-med.com/a181129/) ) (sintilimab, IBI308, developed by
Innovent Biologics, Inc.).

 

 

About Tislelizumab

 

Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody
specifically designed to minimize binding to FcγR on macrophages. In
pre-clinical studies, binding to FcγR on macrophages has been shown to
compromise the anti-tumor activity of PD-1 antibodies through activation of
antibody-dependent macrophage-mediated killing of T effector cells.
Tislelizumab is the first drug from BeiGene's immuno-oncology biologics
program and is being developed internationally as a monotherapy and in
combination with other therapies for the treatment of a broad array of both
solid tumor and hematologic cancers.

 

The NMPA has granted tislelizumab approval in five indications, including full
approval for first-line treatment of patients with advanced squamous non-small
cell lung cancer ("NSCLC") in combination with chemotherapy and for first-line
treatment of patients with advanced non-squamous NSCLC in combination with
chemotherapy; and conditional approval for the treatment of patients with
classical Hodgkin's lymphoma (cHL) who received at least two prior therapies,
for the treatment of patients with locally advanced or metastatic urothelial
carcinoma (UC) with PD-L1 high expression whose disease progressed during or
following platinum-containing chemotherapy or within 12 months of neoadjuvant
or adjuvant treatment with platinum-containing chemotherapy, and for the
treatment of patients with hepatocellular carcinoma (HCC) who have received at
least one systemic therapy. Full approval for these indications is contingent
upon results from ongoing randomized, controlled confirmatory clinical trials.

 

In addition, four supplemental Biologics License Applications for tislelizumab
have been accepted by the Center for Drug Evaluation (CDE) of the NMPA and are
under review for second- or third-line treatment of patients with locally
advanced or metastatic NSCLC who progressed on prior platinum-based
chemotherapy, for patients with previously treated, locally advanced
unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch
repair-deficient (dMMR) solid tumors, for the treatment of patients with
locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who
have disease progression following or are intolerant to first-line standard
chemotherapy, and for first-line treatment of patients with recurrent or
metastatic nasopharyngeal cancer (NPC).

 

BeiGene has initiated or completed 17 potentially registration-enabling
clinical trials in China and globally, including 13 Phase III trials and four
pivotal Phase II trials.

 

In January 2021, BeiGene and Novartis entered into a collaboration and license
agreement granting Novartis rights to develop, manufacture, and commercialize
tislelizumab in North America, Europe, and Japan.

 

Tislelizumab is not approved for use outside of China.

 

 

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. A dedicated
organization of over 1,400 personnel 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 (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 and other federal securities laws, including statements regarding
the clinical development of fruquintinib in combination with tislelizumab,
HUTCHMED's and BeiGene's roles and responsibilities in the collaboration, the
opportunity and potential benefits of their product candidates both as
monotherapies and in combination, and other information that is not historical
information. Actual results may differ materially from those indicated in the
forward-looking statements as a result of various important factors, including
the ability of HUTCHMED and BeiGene to develop and receive regulatory
approvals for the combination therapies in the collaboration; the risk that
the potential benefits of the collaboration do not materialize or do not
outweigh the costs; the ability of HUTCHMED and BeiGene to demonstrate the
efficacy and safety of their respective drug candidates as monotherapies or in
combination; the clinical results for such drug candidates, which may not
support further development or marketing approval; actions of regulatory
agencies, which may affect the initiation, timing and progress of clinical
trials and marketing approval; HUTCHMED's and BeiGene's ability to achieve
commercial success for their marketed products and drug candidates, if
approved; HUTCHMED's and BeiGene's ability to obtain and maintain protection
of intellectual property for their respective technology and drugs; HUTCHMED's
and BeiGene's reliance on third parties to conduct drug development,
manufacturing and other services; HUTCHMED's and BeiGene's limited experience
in obtaining regulatory approvals and commercializing pharmaceutical products
and HUTCHMED's and BeiGene's ability to obtain additional funding for
operations and to complete the development and commercialization of their drug
candidates; and the impact of the COVID-19 pandemic on general economic
regulatory and political conditions and on HUTCHMED's and BeiGene's clinical
development, regulatory, commercial and other operations. 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 or BeiGene's
filings with the U.S. Securities and Exchange Commission, The Stock Exchange
of Hong Kong Limited and, in the case of HUTCHMED, on AIM. All information in
this press release is as of the date of this press release, and neither
HUTCHMED nor BeiGene undertakes a duty to update such information unless
required by law.

 

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, Panmure Gordon (UK) Limited   +44 (20) 7886 2500

 

 

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 4  Mittendorf, E., Philips, A., Funda, M., et al. PD-L1 Expression in
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 8  Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al.
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doi:10.1200/JCO.2012.48.2596

 

 

 

 

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