PRINCETON, N.J., Jan. 25, 2020 /PRNewswire/ -- Taiho
Oncology, Inc. announced today the presentation of a pooled
analysis for hematologic adverse events of the global Phase III
TAGS and RECOURSE trials evaluating LONSURF®
(trifluridine and tipiracil) in patients with metastatic colorectal
cancer (mCRC) and metastatic gastric or gastroesophageal junction
cancer (mGC/GEJC), respectively. The company also presented updates
on two trials in progress with futibatinib, the Phase III
FOENIX-CCA3 study of futibatinib as first-line treatment for
patients with advanced cholangiocarcinoma (CCA) harboring
FGFR 2 gene rearrangements and a Phase II basket study of
futibatinib in patients with advanced solid tumors harboring
FGFR genomic aberrations.
These data were highlighted at the ASCO 2020 Gastrointestinal
Cancers Symposium (ASCO GI) in San
Francisco on January 23-25,
2020.
LONSURF Pooled Safety Analysis
The pooled safety
analysis of the TAGS and RECOURSE trials determined that
hematologic adverse events with LONSURF in subgroups of patients
with mild to moderate renal impairment and mild hepatic impairment
were manageable and similar to those in the overall patient
population.
"Beyond the therapeutic effects of treatment and its impact on
disease progression and survival in people living with cancer, the
safety and tolerability of our medicines are the highest priority
to us," said Karin Blakolmer, MD,
MBA, Senior Vice President and Head of Medical Affairs, Taiho
Oncology, Inc. "For patients treated with LONSURF in the TAGS and
RECOURSE trials, we are pleased to see that hematologic adverse
events for certain subgroups were in line with what we saw in the
overall patient population and, as important, were manageable. This
is good news for people living with metastatic colorectal cancer
and metastatic gastric cancer who are receiving treatment with
LONSURF."
Futibatinib Trials in Progress
The first trial in
progress is FOENIX-CCA3, a Phase III multicenter, open-label,
randomized study that will be conducted in patients with metastatic
or unresectable intrahepatic CCA harboring FGFR2
rearrangements. Approximately 216 patients will be randomized to
receive first-line therapy with 20 mg futibatinib once daily or
gemcitabine and cisplatin for up to 8 cycles. Patients are to be
treated until the first occurrence of disease progression, death or
other protocol specified discontinuation criteria. The primary
endpoint is progression-free survival (PFS). Secondary endpoints
include objective response rate (ORR) and disease control rate and
safety.
The second trial in progress is a Phase II global, open-label
study that will explore treatment with futibatinib in patients
(n=~60) with metastatic or locally advanced solid tumors, except
primary brain tumors or intrahepatic CCA, harboring FGFR1–4
rearrangements and with disease progression after standard
treatment (Cohort A), and in patients (n=~35) with metastatic or
locally advanced gastric tumors harboring FGFR2
amplifications and with two or more lines of prior therapy (Cohort
B). Patients will receive 20 mg of futibatinib once daily in a
continuous 28-day cycle until disease progression, unacceptable
toxicity or other discontinuation criteria are met. The primary
endpoint is independently assessed ORR. Secondary endpoints include
ORR per investigator, disease control rate, duration of response,
PFS, overall survival and safety.
About TAGS
The TAGS (TAS-102
Gastric Study) trial was a
Taiho-sponsored, global, pivotal Phase III, multinational,
randomized, double-blind study evaluating LONSURF (trifluridine and
tipiracil, FTD/TPI), plus best supportive care (BSC) versus placebo
plus BSC in patients with metastatic gastric cancer, including
gastroesophageal junction cancer, refractory to standard
treatments. The primary endpoint in the TAGS trial was overall
survival (OS), and the main secondary endpoint measures included
progression-free survival (PFS), safety and tolerability, as well
as quality of life.
The TAGS trial enrolled 507 adult patients with metastatic
gastric cancer who had previously received at least two prior
regimens for advanced disease. The study was conducted in 17
countries and 110 sites around the world.
About RECOURSE
The RECOURSE trial was a global,
randomized, double-blind, placebo-controlled Phase III comparison
trial evaluating the efficacy and safety of orally administered
LONSURF in patients with previously treated mCRC. The trial
enrolled 800 patients in North
America, Japan,
Europe and Australia. Patients were randomized (2:1) to
receive LONSURF (35 mg/m2) or placebo, plus BSC, twice
daily. The study met its primary and secondary endpoints of OS and
PFS versus placebo.
About Metastatic Colorectal Cancer
Colorectal cancer
is the 4th most commonly diagnosed cancer in
the United States
(U.S.).1 In 2019, there were an estimated 145,600
new cases and 51,020 deaths in the U.S.1 Approximately
22 percent of U.S. patients with colorectal cancer are diagnosed at
the distant or metastasized stage.1 Metastatic
colorectal cancer (mCRC) is associated with poor prognosis with a
five-year survival rate of approximately 14
percent.1
Over the last decade, clinical outcomes for patients with mCRC
have improved considerably due to the advent of novel treatment
agents, predictive biomarkers, and a more strategic approach to the
delivery of systemic therapies. Currently, the median overall
survival for patients with mCRC being treated both in Phase III
trials and in large observational series or registries is 30 months
– more than double that of 20 years ago.2,3,4
About Cholangiocarcinoma
Cholangiocarcinoma (CCA), also known as bile duct cancer, is not
common. About 8,000 people in the U.S. are diagnosed with CCA each
year.5 This includes both intrahepatic (inside the
liver) and extrahepatic (outside the liver) cancers. CCA can occur
at younger ages, but it is seen mainly in older people. The average
age of people in the U.S. diagnosed with cancer of the intrahepatic
bile ducts is 70, and for cancer of the extrahepatic bile ducts it
is 72.5 The chances of survival for patients with CCA
depend to a large extent on its location and how advanced it is
when it is found.5
The main treatment for CCA is surgery. Radiation therapy and
chemotherapy may be used if the cancer cannot be entirely removed
with surgery and in cases where the edges of the tissues removed at
the operation show cancer cells (also called a positive margin).
Both stage III and stage IV cancers cannot be completely removed
surgically. Currently, standard treatment options are limited to
radiation, palliative therapy, liver transplantation, surgery,
chemotherapy and interventional radiology.6
About Metastatic Gastric Cancer
Gastric cancer, also
known as stomach cancer, is the 15th most commonly
diagnosed cancer in the U.S.7 In 2019, there were
an estimated 27,510 new cases and 11,140 deaths. Approximately 62
percent of U.S. patients with gastric cancer are diagnosed at
advanced disease. Metastatic gastric cancer (mGC) is associated
with a five-year survival rate of about 5 percent.7
In the U.S., standard chemotherapy regimens for advanced gastric
cancer include fluoropyrimidines, platinum derivatives, and taxanes
(with ramucirumab), or irinotecan. After failure of first- and
second-line therapies, subsequent treatment options are
limited.
About Gastroesophageal Junction
Cancer
Gastroesophageal junction cancer is a type of cancer
that begins in cells located near the gastroesophageal junction,
the area where the esophagus connects to the
stomach.8 It remains a significant clinical problem
that is increasing in incidence and is associated with a poor
prognosis. The majority of patients present with advanced disease,
and less than 50 percent undergo curative
treatment.9
About Futibatinib (TAS-120)
Futibatinib (TAS-120) is
an investigational, oral, potent, selective, and irreversible
small-molecule inhibitor of FGFR1, 2, 3, and 4 being studied
as a potential treatment for patients with advanced solid tumors,
including cholangiocarcinoma, who were previously treated with
chemotherapy or other therapies including other FGFR
inhibitors. Futibatinib selectively and irreversibly binds to
the ATP binding pocket of FGFR 1-4 resulting in the
inhibition of FGFR-mediated signal transduction pathways,
reduced tumor cell proliferation and increased tumor cell death in
tumors with FGFR1-4 genomic aberrations.
About LONSURF10
LONSURF is an oral nucleoside antitumor agent discovered and
developed by Taiho Pharmaceutical Co., Ltd. LONSURF consists of a
thymidine-based nucleoside analog, trifluridine, and the thymidine
phosphorylase (TP) inhibitor, tipiracil, which increases
trifluridine exposure by inhibiting its metabolism by TP.
Trifluridine is incorporated into DNA, resulting in DNA dysfunction
and inhibition of cell proliferation.
Since 2015, Taiho Pharmaceutical and Servier have been in an
exclusive license agreement for the co-development and
commercialization of LONSURF in Europe and other countries outside of
the United States, Canada, Mexico, and Asia.
Indications and Use
LONSURF is indicated for the
treatment of adult patients with:
- metastatic colorectal cancer previously treated with
fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy,
an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR
therapy
- metastatic gastric or gastroesophageal junction adenocarcinoma
previously treated with at least two prior lines of chemotherapy
that included a fluoropyrimidine, a platinum, either a taxane or
irinotecan, and if appropriate, HER2/neu-targeted therapy.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Severe Myelosuppression:
LONSURF caused severe and life‑threatening myelosuppression
(Grade 3‑4) consisting of neutropenia (38%), anemia (18%),
thrombocytopenia (5%), and febrile neutropenia (3%). Two patients
(0.2%) died due to neutropenic infection. A total of 12% of
LONSURF‑treated patients received granulocyte‑colony stimulating
factors. Obtain complete blood counts prior to and on day 15 of
each cycle of LONSURF and more frequently as clinically indicated.
Withhold LONSURF for febrile neutropenia, absolute neutrophil count
less than 500/mm3, or platelets less than
50,000/mm3. Upon recovery, resume LONSURF at a reduced
dose as clinically indicated.
Embryo‑Fetal Toxicity:
LONSURF can cause fetal harm when administered to a pregnant
woman. Advise pregnant women of the potential risk to the fetus.
Advise females of reproductive potential to use effective
contraception during treatment and for at least 6 months after the
final dose.
USE IN SPECIFIC POPULATIONS
Lactation: It is not known whether LONSURF or its
metabolites are present in human milk. There are no data to assess
the effects of LONSURF or its metabolites on the breast‑fed infant
or the effects on milk production. Because of the potential for
serious adverse reactions in breast‑fed infants, advise women not
to breastfeed during treatment with LONSURF and for 1 day following
the final dose.
Male Contraception: Because of the potential for
genotoxicity, advise males with female partners of reproductive
potential to use condoms during treatment with LONSURF and for at
least 3 months after the final dose.
Geriatric Use: Patients 65 years of age or over who
received LONSURF had a higher incidence of the following compared
to patients younger than 65 years: Grade 3 or 4 neutropenia (46% vs
32%), Grade 3 anemia (22% vs 16%), and Grade 3 or 4
thrombocytopenia (7% vs 4%).
Hepatic Impairment: Do not initiate LONSURF in patients
with baseline moderate or severe (total bilirubin greater than 1.5
times ULN and any AST) hepatic impairment. Patients with severe
hepatic impairment (total bilirubin greater than 3 times ULN and
any AST) were not studied. No adjustment to the starting dose of
LONSURF is recommended for patients with mild hepatic
impairment.
Renal Impairment: No adjustment to the starting
dosage of LONSURF is recommended in patients with mild or moderate
renal impairment (CLcr of 30 to 89 mL/min). Reduce the starting
dose of LONSURF for patients with severe renal impairment (CLcr of
15 to 29 mL/min) to a recommended dosage of 20
mg/m2.
ADVERSE REACTIONS
Most Common Adverse Drug Reactions in Patients Treated With
LONSURF (≥5%): The most common adverse drug reactions in
LONSURF‑treated patients vs placebo‑treated patients with mCRC,
respectively, were asthenia/fatigue (52% vs 35%), nausea (48% vs
24%), decreased appetite (39% vs 29%), diarrhea (32% vs 12%),
vomiting (28% vs 14%), infections (27% vs 16%), abdominal pain (21%
vs 18%), pyrexia (19% vs 14%), stomatitis (8% vs 6%), dysgeusia (7%
vs 2%), and alopecia (7% vs 1%). In metastatic gastric cancer or
gastroesophageal junction (GEJ), the most common adverse drug
reactions, respectively were, nausea (37% vs 32%), decreased
appetite (34% vs 31%), vomiting (25% vs 20%), infections (23% vs
16%) and diarrhea (23% vs 14%).
Pulmonary emboli occurred more frequently in LONSURF‑treated
patients compared to placebo: in mCRC (2% vs 0%) and in
metastatic gastric cancer and GEJ (3% vs 2%).
Interstitial lung disease (0.2%), including fatalities, has been
reported in clinical studies and clinical practice settings in
Asia.
Laboratory Test Abnormalities in Patients Treated With
LONSURF: The most common laboratory test abnormalities in
LONSURF‑treated patients vs placebo-treated patients with mCRC,
respectively, were anemia (77% vs 33%), neutropenia (67% vs 1%),
and thrombocytopenia (42% vs 8%). In metastatic gastric
cancer or GEJ, the test abnormalities, respectively, were
neutropenia (66% vs 4%), anemia (63% vs 38%), and thrombocytopenia
(34% vs 9%).
Please see full Prescribing
Information.
https://www.taihooncology.com/us/prescribing-information.pdf
About Taiho Oncology, Inc. (U.S.)
Taiho Oncology,
Inc., a subsidiary of Taiho Pharmaceutical Co., Ltd. and Otsuka
Holdings Co., Ltd., has established a world class clinical
development organization that works urgently to develop innovative
cancer treatments and has built a commercial business in the U.S.
Taiho has an oral oncology pipeline consisting of both novel
antimetabolic agents and selectively targeted agents. Advanced
technology, dedicated researchers, and state of the art facilities
are helping us to define the way the world treats cancer. It's our
work; it's our passion; it's our legacy.
For more information about Taiho Oncology, please visit:
https://www.taihooncology.com/us/
For more information about Taiho Pharmaceutical Co., Ltd.,
please visit:
https://www.taiho.co.jp/en/
For more information about Otsuka Holdings Co., Ltd., please
visit:
https://www.otsuka.com/en/
For more information about Servier, please visit:
https://www.servier.com/en/
U.S. Media Contact:
Craig
Heit
GCI Health on behalf of Taiho Oncology
Taihooncology@gcihealth.com
212-798-9919
LON-PM-US-1337 01/20
1 National Cancer Institute Surveillance
Epidemiology and End Results Program. Cancer Stat Facts: Colon and
Rectum Cancer.
https://seer.cancer.gov/statfacts/html/colorect.html. Accessed
December 2019.
2 Brenner H, Kloor M, Pox CP. Colorectal cancer.
Lancet. 2014;383(9927):1490-1502.
3 Price TJ, Segelov E, Burge M, et al. Current
opinion on optimal systemic treatment for metastatic colorectal
cancer: outcome of the ACTG/AGITG expert meeting ECCO 2013.
Expert review of anticancer therapy.
2014;14(12):1477-1493.
4 Van Cutsem E, Cervantes A, Adam R, et al. ESMO
consensus guidelines for the management of patients with metastatic
colorectal cancer. Ann Oncol. 2016;27(8):1386-1422.
5 American Cancer Society; What are the key
statistics about bile duct cancer?
https://www.cancer.org/cancer/bile-duct-cancer/about/key-statistics.html#references.
Accessed December 2019.
6 The Cholangiocarcinoma Foundation. Treatment
Options.
https://cholangiocarcinoma.org/the-disease/treatment-options.
Accessed December 2019.
7 National Cancer Institute Surveillance Epidemiology
and End Results Program. Cancer Stat Facts: Stomach Cancer.
https://seer.cancer.gov/statfacts/html/stomach.html. Accessed
April 26, 2019.
8 The Migration of Gastric Cancer to the GE
Junction. Johns Hopkins Surgery. Summer 2014.
https://www.hopkinsmedicine.org/news/publications/johns_hopkins_surgery/johns_hopkins_surgery_summer_2014/the_migration_of_gastric_cancer_to_the_ge_junction.
Accessed December 2019.
9 Barbour A, Rizk, N, Gonen, M, et al.
Adenocarcinoma of the gastroesophageal junction. Ann
Surg. 2007 Jul; 246(1): 1-8.
10 LONSURF [US prescribing information];
Princeton, NJ: Taiho Oncology,
Inc.; 2019. 2019.
View original content to download
multimedia:http://www.prnewswire.com/news-releases/taiho-oncology-presents-data-on-lonsurf-trifluridine-and-tipiracil-and-futibatinib-tas-120-at-asco-2020-gastrointestinal-cancers-symposium-asco-gi-300993200.html
SOURCE Taiho Oncology, Inc.