INDIANAPOLIS, Jan. 13, 2020 /PRNewswire/ -- Today, Eli
Lilly and Company (NYSE: LLY) jointly announced with Innovent
Biologics, Inc. the results of a Phase 3 study in China; the ORIENT-11 trial of
Tyvyt® (sintilimab injection) in combination with
ALIMTA® (pemetrexed) and platinum in first-line advanced
or recurrent nonsquamous non-small cell lung cancer (nsqNSCLC),
without sensitive EGFR mutation or ALK rearrangement, met the
predefined primary endpoint of progression-free survival (PFS) in
an interim analysis.
Based on the interim analysis conducted by the Independent Data
Monitoring Committee (IDMC), sintilimab in combination with ALIMTA
and platinum demonstrated a statistically significant improvement
in PFS compared with placebo in combination with ALIMTA and
platinum, which met the pre-defined efficacy criteria. The safety
profile of sintilimab in this trial was consistent with previously
reported studies, and no new safety signals were identified.
Relevant data will be presented at an upcoming medical
conference. Based on the IDMC recommendations, Lilly and Innovent
will initiate regulatory discussions for registration with the
National Medical Products Administration (NMPA) in China in the near future.
Professor Li Zhang, Head of the
Department of Internal Medicine, Sun
Yat-sen University Cancer Center, stated: "In 2019, the
National Cancer Center published Chinese data on lung cancer from
2015, showing an incidence of 20 percent and a mortality rate of
about 27 percent, ranking it first among all cancer types. Patients
who have nsqNSCLC without sensitive EGFR mutation or ALK
rearrangement need more treatment options. Treatment with an
anti-PD-1 monoclonal antibody in combination with chemotherapy may
bring a greater survival benefit to this patient population. We are
glad to see that these findings from this trial of sintilimab met
the predefined primary endpoint in the interim analysis."
"We are excited about these results, which show Tyvyt plus
ALIMTA and platinum significantly delayed disease progression in
this patient population. This study is another example of the joint
commitment from Lilly and Innovent to provide new treatment options
to patients with lung cancer," said Dr. Wang Li, Senior Vice-President of Lilly China and Head of Lilly China Drug
Development and Medical Affairs. "We would like to thank the
patients, investigators and clinical trial sites that are
participating in the study, and our colleagues from Innovent. We
look forward to bringing this new treatment option to lung cancer
patients in China."
Dr. Hui Zhou, Vice President and
Head of Oncology Strategy and Medical Sciences, Innovent,
said: "So far, Tyvyt is the only anti-PD-1 monoclonal antibody
included in the New Catalogue of the National Reimbursement Drug
List. It was officially approved by the NMPA on December 24, 2018 for the treatment of relapsed
or refractory classic Hodgkin's lymphoma after at least second-line
system chemotherapy. Currently, we have several ongoing
Phase 3 randomized clinical trials in lung cancer. With
the encouraging result of ORIENT-11 we anticipate that sintilimab
has the potential to benefit more patients with lung cancer and
provide them more time with their families."
About ORIENT-11 Trial
ORIENT-11 is a randomized,
double-blind, Phase 3 clinical trial to evaluate the efficacy and
safety of Tyvyt (sintilimab injection) or placebo in combination
with ALIMTA and platinum as first-line therapy for advanced or
recurrent nsqNSCLC without sensitive EGFR mutation or ALK
rearrangement (ClinicalTrials.gov, NCT03607539). The primary
endpoint is progression-free survival (PFS) assessed by the
Independent Radiographic Review Committee (IRRC) based on RECIST
v1.1. The other secondary endpoints include overall survival (OS)
and safety profile.
A total of 397 subjects have been enrolled in the ORIENT-11
trial and randomized in a 2:1 ratio to receive either sintilimab
200mg or placebo in combination with ALIMTA and platinum
every three weeks for up to four cycles, followed by
either sintilimab or placebo plus ALIMTA maintenance therapy. The
subjects will receive treatment until radiographic disease
progression, unacceptable toxicity or any other conditions that
require treatment discontinuation. Conditional crossover is
permitted.
About nsqNSCLC
Lung cancer is a malignancy with the
highest morbidity and mortality rates in China. NSCLC accounts for about 80 percent to
85 percent of lung cancers. Approximately 70 percent of NSCLC are
locally advanced or metastatic at initial diagnosis, rendering the
patients with no chance of radical resection. Meanwhile, even after
radical surgery patients still have a high chance of recurrence and
eventually die from disease progression. About 70 percent of NSCLC
in China are nonsquamous subtype
and 50 percent of nsqNSCLC are without sensitive EGFR mutation or
ALK rearrangement. These patients do not respond well to targeted
therapy and there are limited treatment options available to
them.
About Tyvyt® (Sintilimab Injection)
Tyvyt® (sintilimab injection), an innovative drug
jointly developed in China by
Innovent and Lilly, has been granted marketing approval by the NMPA
for relapsed or refractory classic Hodgkin's lymphoma after at
least second-line system chemotherapy, and is included in
the 2019 Guidelines of Chinese Society of Clinical Oncology for
Lymphoid Malignancies. Tyvyt is the only PD-1 inhibitor with global
quality that has been included in the new Catalogue of the National
Reimbursement Drug List (NRDL) in November
2019.
Tyvyt 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. Innovent is currently conducting more than 20
clinical studies for sintilimab injection to evaluate its safety
and efficacy in a wide variety of cancer indications, including
eight registration or pivotal clinical trials.
Tyvyt (sintilimab injection) is not an approved product in
the United States. ALIMTA®
(pemetrexed for injection) is not approved for use in combination
with Tyvyt in the United States.
U.S. INDICATIONS FOR ALIMTA® (pemetrexed for
injection)
ALIMTA is indicated:
- in combination with pembrolizumab and platinum chemotherapy for
the initial treatment of patients with nonsquamous metastatic
non-small cell lung cancer (mNSCLC) with no EGFR or ALK genomic
tumor aberrations.
- in combination with cisplatin for the initial treatment of
patients with locally advanced or metastatic nonsquamous non-small
cell lung cancer (NSCLC).
- as a single agent for the maintenance treatment of patients
with locally advanced or metastatic nonsquamous non-small cell lung
cancer (NSCLC) whose disease has not progressed after four cycles
of platinum-based first-line chemotherapy.
- as a single agent for the treatment of patients with recurrent
metastatic nonsquamous non-small cell lung cancer (NSCLC) after
prior chemotherapy. Limitation of Use: ALIMTA is not indicated for
the treatment of patients with squamous cell non-small cell lung
cancer.
- in combination with cisplatin, for the initial treatment of
patients with malignant pleural mesothelioma (MPM) whose disease is
unresectable or who are otherwise not candidates for curative
surgery.
U.S. IMPORTANT SAFETY INFORMATION FOR ALIMTA®
(pemetrexed for injection)
CONTRAINDICATION
- ALIMTA is contraindicated in patients who have a history of
severe hypersensitivity reaction to pemetrexed.
WARNINGS AND PRECAUTIONS
Myelosuppression and Increased Risk of Myelosuppression
Without Vitamin Supplementation
- ALIMTA can cause severe myelosuppression resulting in a
requirement for transfusions and which may lead to neutropenic
infection. The risk of myelosuppression is increased in patients
who do not receive vitamin supplementation.
- Prior to treatment with ALIMTA, patients must be instructed to
initiate supplementation with oral folic acid. Intramuscular
injections of vitamin B12 are also required prior to
ALIMTA treatment. Folic acid and vitamin B12
supplementation should be continued during treatment and for 21
days after the last dose of ALIMTA as they may reduce the severity
of treatment-related hematologic and gastrointestinal toxicities.
Obtain a complete blood count at the beginning of each cycle. Do
not administer ALIMTA until the ANC is at least 1500
cells/mm3 and platelet count is at least 100,000
cells/mm3. Permanently reduce ALIMTA in patients with an
ANC of less than 500 cells/mm3 or platelet count of less
than 50,000 cells/mm3 in previous cycles.
- In Studies JMDB and JMCH, among patients who received vitamin
supplementation, incidence of Grade 3-4 neutropenia was 15% and
23%, the incidence of Grade 3-4 anemia was 6% and 4%, and incidence
of Grade 3-4 thrombocytopenia was 4% and 5%, respectively. In Study
JMCH, 18% of patients in the ALIMTA arm required red blood cell
transfusions compared to 7% of patients in the cisplatin arm. In
Studies JMEN, PARAMOUNT, and JMEI, where all patients received
vitamin supplementation, incidence of Grade 3-4 neutropenia ranged
from 3% to 5%, and incidence of Grade 3-4 anemia ranged from 3% to
5%.
Renal Failure
- ALIMTA can cause severe, and sometimes fatal, renal toxicity.
Determine creatinine clearance before each dose and periodically
monitor renal function during treatment with ALIMTA.
- The incidences of renal failure in clinical studies in which
patients received ALIMTA with cisplatin were 2.1% in Study JMDB and
2.2% in Study JMCH. The incidence of renal failure in clinical
studies in which patients received ALIMTA as a single agent ranged
from 0.4% to 0.6% (Studies JMEN, PARAMOUNT, and JMEI).
- Withhold ALIMTA in patients with a creatinine clearance of less
than 45 mL/min.
Bullous and Exfoliative Skin Toxicity
- Serious and sometimes fatal, bullous, blistering, and
exfoliative skin toxicity, including cases suggestive of
Stevens-Johnson Syndrome/toxic epidermal necrolysis, can occur with
ALIMTA. Permanently discontinue ALIMTA for severe and
life-threatening bullous, blistering, or exfoliating skin
toxicity.
Interstitial Pneumonitis
- Serious interstitial pneumonitis, including fatal cases, can
occur with ALIMTA treatment. Withhold ALIMTA for acute onset of new
or progressive unexplained pulmonary symptoms such as dyspnea,
cough, or fever pending diagnostic evaluation. If pneumonitis is
confirmed, permanently discontinue ALIMTA.
Radiation Recall
- Radiation recall can occur with ALIMTA in patients who have
received radiation weeks to years previously. Monitor patients for
inflammation or blistering in areas of previous radiation
treatment. Permanently discontinue ALIMTA for signs of radiation
recall.
Increased Risk of Toxicity With Ibuprofen in Patients With
Renal Impairment
- Exposure to ALIMTA is increased in patients with mild to
moderate renal impairment who take concomitant ibuprofen,
increasing the risks of adverse reactions of ALIMTA. In patients
with creatinine clearances between 45 mL/min and 79 mL/min, avoid
administration of ibuprofen for 2 days before, the day of, and 2
days following administration of ALIMTA. If concomitant ibuprofen
use cannot be avoided, monitor patients more frequently for ALIMTA
adverse reactions, including myelosuppression, renal, and
gastrointestinal toxicity.
Embryo-Fetal Toxicity
- Based on findings from animal studies and its mechanism of
action, ALIMTA can cause fetal harm when administered to a pregnant
woman. In animal reproduction studies, intravenous administration
of pemetrexed to pregnant mice during the period of organogenesis
was teratogenic, resulting in developmental delays and increased
malformations at doses lower than the recommended human dose of 500
mg/m2. Advise pregnant women of the potential risk to
the fetus. Advise females of reproductive potential to use
effective contraception during treatment with ALIMTA and for 6
months after the final dose. Advise males with female partners of
reproductive potential to use effective contraception during
treatment with ALIMTA and for 3 months after the final dose.
DRUG INTERACTIONS
- Ibuprofen increases exposure (AUC) of pemetrexed. In patients
with creatinine clearance between 45 mL/min and 79 mL/min:
- Avoid administration of ibuprofen for 2 days before, the day
of, and 2 days following administration of ALIMTA.
- Monitor patients more frequently for myelosuppression, renal,
and gastrointestinal toxicity, if concomitant administration of
ibuprofen cannot be avoided.
ADVERSE REACTIONS
- Severe adverse reactions (Grade 3-4) occurring in ≥20% of
patients with metastatic nonsquamous non-small cell lung cancer
(NSCLC) receiving ALIMTA in combination with pembrolizumab and
platinum chemotherapy (carboplatin or cisplatin) versus ALIMTA with
platinum chemotherapy + placebo for initial treatment
(KEYNOTE-189), respectively, were fatigue (12% vs 6%); diarrhea (5%
vs 3%); dyspnea (3.7% vs 5%); vomiting (3.7% vs 3%); nausea (3.5%
vs 3.5%); rash (2% vs 2.5%); decreased appetite (1.5% vs 0.5%);
constipation (1% vs 0.5%); and pyrexia (0.2% vs 0%).
- Common adverse reactions (all grades) occurring in ≥20% of
patients with metastatic nonsquamous non-small cell lung cancer
(NSCLC) receiving ALIMTA in combination with pembrolizumab and
platinum chemotherapy (carboplatin or cisplatin) versus ALIMTA with
platinum chemotherapy + placebo for initial treatment
(KEYNOTE-189), respectively, were nausea (56% vs 52%); fatigue (56%
vs 58%); constipation (35% vs 32%); diarrhea (31% vs 21%);
decreased appetite (28% vs 30%); rash (25% vs 17%); vomiting (24%
vs 23%); cough (21% vs 28%); dyspnea (21% vs 26%); and pyrexia (20%
vs 15%).
USE IN SPECIFIC PATIENT POPULATIONS
- Lactation: There is no information regarding the
presence of pemetrexed or its metabolites in human milk, the
effects on the breastfed infant, or the effects on milk production.
Because of the potential for serious adverse reactions in breastfed
infants from ALIMTA, advise women not to breastfeed during
treatment with ALIMTA and for one week after the last dose.
- Males of Reproductive Potential: ALIMTA may impair
fertility in males of reproductive potential. It is not known
whether these effects on fertility are reversible.
- Pediatric Use: The safety and effectiveness of ALIMTA in
pediatric patients have not been established. Adverse reactions
observed in pediatric patients studied were similar to those
observed in adults.
- Patients with Renal Impairment: ALIMTA is primarily
excreted by the kidneys. Decreased renal function results in
reduced clearance and greater exposure (AUC) to ALIMTA compared
with patients with normal renal function. No dose is recommended
for patients with creatinine clearance less than 45 mL/min.
- Geriatric: The incidences of Grade 3-4 anemia, fatigue,
thrombocytopenia, hypertension, and neutropenia were higher in
patients 65 years of age and older as compared to younger patients:
in at least one of five randomized clinical trials.
PM_HCP_ISI_NSCLC1L_Combo_30JAN2019
For U.S. safety and dosing guidelines for ALIMTA, see
complete Warnings and Precautions, Adverse Reactions, and Dosage
and Administration sections in the full U.S. Prescribing
Information and Patient Prescribing Information.
ALIMTA® is a registered trademark owned by or
licensed to Eli Lilly and Company, its subsidiaries, or
affiliates.
About Lilly Oncology
For more than 50 years, Lilly
has been dedicated to delivering life-changing medicines and
support to people living with cancer and those who care for them.
Lilly is determined to build on this heritage and continue making
life better for all those affected by cancer around the world. To
learn more about Lilly's commitment to people with cancer, please
visit www.LillyOncology.com.
About Eli Lilly and Company
Lilly is a global health care leader that unites caring with
discovery to create medicines that make life better for people
around the world. We were founded more than a century ago by a man
committed to creating high-quality medicines that meet real needs,
and today we remain true to that mission in all our work. Across
the globe, Lilly employees work to discover and bring life-changing
medicines to those who need them, improve the understanding and
management of disease, and give back to communities through
philanthropy and volunteerism. To learn more about Lilly, please
visit us at lilly.com and lilly.com/newsroom.
About Innovent
Inspired by the spirit of "Start with
Integrity, Succeed through Action," Innovent's mission is to
develop and commercialize high quality biopharmaceutical products
that are affordable to ordinary people. Established in 2011,
Innovent is committed to developing, manufacturing and
commercializing high quality innovative medicines for the treatment
of oncology, autoimmune, metabolic and other major diseases. On
October 31, 2018, Innovent was listed
on the Main Board of the Stock Exchange of Hong Kong Limited with
the stock code: 01801.HK.
Since it was founded, Innovent has developed a fully-integrated
platform which includes R&D, CMC (Chemistry, Manufacturing, and
Controls), clinical development and commercialization capabilities.
Leveraging the platform, the company has built a robust pipeline of
21 innovative assets in the fields of oncology, autoimmune,
metabolic diseases and other major therapeutic areas, with sixteen
in clinical development, five in Phase III clinical trials, three
NDAs under review by NMPA with priority review status, while
Tyvyt®, officially approved for marketing in China in 2018, has been the only PD-1
inhibitor included in the NRDL since 2019.
Innovent has built an international team of advanced talents in
high-end biological drug development and commercialization,
including many overseas experts. The company has also entered into
strategic collaborations with Eli Lilly and Company, Adimab,
Incyte, Hanmi and other international pharmaceutical companies.
Innovent strives to work with all relevant parties to help advance
China's biopharmaceutical industry, improve drug availability to
ordinary people and enhance the quality of the patients' lives. For
more information, please visit:www.innoventbio.com.
About Innovent Biologics' strategic cooperation with Eli
Lilly and Company
Eli Lilly and Company launched a program
focusing on biological medicine co-development with Innovent
Biologics in March 2015 – a
groundbreaking partnership between a Chinese pharmaceutical company
and a multinational pharmaceutical company. Under the agreement,
Lilly and Innovent Biologics will co-develop and commercialize
oncology medicines, including Tyvyt in China. In October
2015, the two companies announced the extension of their
existing collaboration to include co-development of three
additional antibodies targeting oncology indications. Its
collaboration with Lilly indicates that Innovent Biologics has
established a comprehensive level of cooperation between China's
innovative pharmaceuticals sector and the international
pharmaceuticals sector in fields such as R&D, pipeline quality
and commercial.
P-LLY
© Lilly USA, LLC 2019. ALL
RIGHTS RESERVED.
Lilly Forward-Looking Statement
This press release
contains forward-looking statements (as that term is defined in the
Private Securities Litigation Reform Act of 1995) about the
ORIENT-11 trial and Tyvyt® (sintilimab injection) in
combination with ALIMTA®(pemetrexed) and
platinum in first-line advanced or recurrent nonsquamous
non-small cell lung cancer, and reflects Lilly's current beliefs.
However, as with any pharmaceutical product, there are substantial
risks and uncertainties in the process of development and
commercialization. Among other things, there can be no guarantee
that Tyvyt will receive regulatory approval for first-line advanced
or recurrent nonsquamous non-small cell lung cancer or will be
commercially successful. For further discussion of these and other
risks and uncertainties, see Lilly's most recent Form 10-K and Form
10-Q filings with the United States Securities and Exchange
Commission. Except as required by law, Lilly undertakes no duty to
update forward- looking statements to reflect events after the date
of this release.
Contact:
Media:
Innovent: pr@innoventbio.com; +86 512-6956
6088
Lilly: Carole Copeland;
Carole_Copeland@Lilly.com; (317) 610-6196
Investors:
Innovent: ir@innoventbio.com; +86 512-6956
6088
Lilly: Kevin Hern;
hern_kevin_r@lilly.com; (317) 277-1838
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