-- Phase 1/2 Study Planned for 2018
--
Kite, a Gilead Company (Nasdaq: GILD), announced it has entered
into a clinical trial collaboration with Pfizer, Inc. to evaluate
the safety and efficacy of the investigational combination of
Yescarta™ (axicabtagene ciloleucel) and Pfizer's utomilumab, a
fully humanized 4-1BB agonist monoclonal antibody, in patients with
refractory large B-cell lymphoma. A multi-center Phase 1/2 study
sponsored by Kite is expected to begin in 2018. The results of this
study will be used to evaluate options for further development of
this combination, or similar combinations between Kite’s engineered
T cell products and utomilumab.
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the full release here:
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Yescarta is the first chimeric antigen receptor T (CAR T) cell
therapy to be indicated for the treatment of adult patients with
relapsed or refractory large B-cell lymphoma after two or more
lines of systemic therapy, including DLBCL not otherwise specified,
primary mediastinal large B-cell lymphoma, high grade B-cell
lymphoma and DLBCL arising from follicular lymphoma. Yescarta is
not indicated for patients with primary central nervous system
lymphoma.
Utomilumab, also known as PF-05082566, is an investigational
4-1BB agonist that has been shown in preclinical models to enhance
T cell mediated immune responses. Pfizer is currently investigating
utomilumab in both hematologic cancers and solid tumors as a single
agent and in combination with other anti-cancer therapies. Evidence
also suggests that 4-1BB, a costimulatory protein expressed on
activated T cells, is upregulated upon exposure to CD19-expressing
tumor cells. Utomilumab could potentially enhance T cell
proliferation and activity by augmenting the CD28 costimulatory
domain of Yescarta with exogenous 4-1BB signaling.
“Kite is committed to realizing the full potential of Yescarta
and other cell therapy technologies across a range of cancers,”
said David Chang, MD, PhD, Worldwide Head of Research and
Development and Chief Medical Officer at Kite. “We are pleased to
collaborate with Pfizer on this study with utomilumab, which adds
to the growing number of combination approaches we are exploring
with Yescarta for patients living with lymphoma.”
The combination of Yescarta and utomilumab is investigational
and has not been proven safe and effective.
U.S. Important Safety Information for
Yescarta
BOXED WARNING: CYTOKINE RELEASE SYNDROME and
NEUROLOGIC TOXICITIES
- Cytokine Release Syndrome (CRS),
including fatal or life-threatening reactions, occurred in patients
receiving Yescarta. Do not administer Yescarta to patients with
active infection or inflammatory disorders. Treat severe or
life-threatening CRS with tocilizumab or tocilizumab and
corticosteroids.
- Neurologic toxicities, including
fatal or life-threatening reactions, occurred in patients receiving
Yescarta, including concurrently with CRS or after CRS resolution.
Monitor for neurologic toxicities after treatment with Yescarta.
Provide supportive care and/or corticosteroids as needed.
- Yescarta is available only through a
restricted program under a Risk Evaluation and Mitigation Strategy
(REMS) called the Yescarta REMS.
Cytokine Release Syndrome (CRS)
CRS, including fatal or life-threatening reactions, occurred
following treatment with Yescarta. In Study 1, CRS occurred in 94%
(101/108) of patients receiving Yescarta, including ≥ Grade 3 (Lee
grading system) CRS in 13% (14/108) of patients. Among patients who
died after receiving Yescarta, four had ongoing CRS events at the
time of death. The median time to onset was 2 days (range: 1 to 12
days) and the median duration of CRS was 7 days (range: 2 to 58
days). Key manifestations of CRS include fever (78%), hypotension
(41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious
events that may be associated with CRS include cardiac arrhythmias
(including atrial fibrillation and ventricular tachycardia),
cardiac arrest, cardiac failure, renal insufficiency, capillary
leak syndrome, hypotension, hypoxia, and hemophagocytic
lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
Ensure that 2 doses of tocilizumab are available prior to
infusion of Yescarta. Monitor patients at least daily for 7 days at
the certified healthcare facility following infusion for signs and
symptoms of CRS. Monitor patients for signs or symptoms of CRS for
4 weeks after infusion. Counsel patients to seek immediate medical
attention should signs or symptoms of CRS occur at any time. At the
first sign of CRS, institute treatment with supportive care,
tocilizumab or tocilizumab and corticosteroids as indicated.
Neurologic Toxicities
Neurologic toxicities, that were fatal or life-threatening,
occurred following treatment with Yescarta. Neurologic toxicities
occurred in 87% of patients. Ninety-eight percent of all neurologic
toxicities occurred within the first 8 weeks of Yescarta infusion,
with a median time to onset of 4 days (range: 1 to 43 days). The
median duration of neurologic toxicities was 17 days. Grade 3 or
higher neurologic toxicities occurred in 31% of patients.
The most common neurologic toxicities included encephalopathy
(57%), headache (44%), tremor (31%), dizziness (21%), aphasia
(18%), delirium (17%), insomnia (9%) and anxiety (9%). Prolonged
encephalopathy lasting up to 173 days was noted. Serious events
including leukoencephalopathy and seizures occurred with Yescarta.
Fatal and serious cases of cerebral edema have occurred in patients
treated with Yescarta.
Monitor patients at least daily for 7 days at the certified
healthcare facility following infusion for signs and symptoms of
neurologic toxicities. Monitor patients for signs or symptoms of
neurologic toxicities for 4 weeks after infusion and treat
promptly.
Yescarta REMS
Because of the risk of CRS and neurologic toxicities, Yescarta
is available only through a restricted program under a Risk
Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS.
The required components of the Yescarta REMS are:
- Healthcare facilities that dispense and
administer Yescarta must be enrolled and comply with the REMS
requirements. Certified healthcare facilities must have on-site,
immediate access to tocilizumab, and ensure that a minimum of two
doses of tocilizumab are available for each patient for infusion
within 2 hours after Yescarta infusion, if needed for treatment of
CRS.
- Certified healthcare facilities must
ensure that healthcare providers who prescribe, dispense or
administer Yescarta are trained about the management of CRS and
neurologic toxicities.
Further information is available at www.YescartaREMS.com or
1-844-454-KITE (5483).
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of Yescarta.
Serious hypersensitivity reactions including anaphylaxis, may be
due to dimethyl sulfoxide (DMSO) or residual gentamicin in
Yescarta.
Serious Infections
Severe or life-threatening infections occurred in patients after
Yescarta infusion. In Study 1, infections (all grades) occurred in
38% of patients. Grade 3 or higher infections occurred in 23% of
patients. Grade 3 or higher infections with an unspecified pathogen
occurred in 16% of patients, bacterial infections in 9%, and viral
infections in 4%. Yescarta should not be administered to patients
with clinically significant active systemic infections. Monitor
patients for signs and symptoms of infection before and after
Yescarta infusion and treat appropriately. Administer prophylactic
anti-microbials according to local guidelines.
Febrile neutropenia was observed in 36% of patients after
Yescarta infusion and may be concurrent with CRS. In the event of
febrile neutropenia, evaluate for infection and manage with broad
spectrum antibiotics, fluids and other supportive care as medically
indicated.
Viral Reactivation
Hepatitis B virus (HBV) reactivation, in some cases resulting in
fulminant hepatitis, hepatic failure and death, can occur in
patients treated with drugs directed against B cells. Perform
screening for HBV, HCV, and HIV in accordance with clinical
guidelines before collection of cells for manufacturing.
Prolonged Cytopenias
Patients may exhibit cytopenias for several weeks following
lymphodepleting chemotherapy and Yescarta infusion. In Study 1,
Grade 3 or higher cytopenias not resolved by Day 30 following
Yescarta infusion occurred in (28%) of patients and included
thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor
blood counts after Yescarta infusion.
Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can occur in patients
receiving treatment with Yescarta. In Study 1,
hypogammaglobulinemia occurred in 15% of patients. Monitor
immunoglobulin levels after treatment with Yescarta and manage
using infection precautions, antibiotic prophylaxis and
immunoglobulin replacement.
The safety of immunization with live viral vaccines during or
following Yescarta treatment has not been studied. Vaccination with
live virus vaccines is not recommended for at least 6 weeks prior
to the start of lymphodepleting chemotherapy, during Yescarta
treatment, and until immune recovery following treatment with
Yescarta.
Secondary Malignancies
Patients treated with Yescarta may develop secondary
malignancies. Monitor life-long for secondary malignancies. In the
event that a secondary malignancy occurs, contact Kite at
1-844-454-KITE (5483) to obtain instructions on patient samples to
collect for testing.
Effects on Ability to Drive and Use Machines
Due to the potential for neurologic events, including altered
mental status or seizures, patients receiving Yescarta are at risk
for altered or decreased consciousness or coordination in the 8
weeks following Yescarta infusion. Advise patients to refrain from
driving and engaging in hazardous occupations or activities, such
as operating heavy or potentially dangerous machinery, during this
initial period.
Adverse Reactions
The most common adverse reactions (incidence ≥ 20%) include CRS,
fever, hypotension, encephalopathy, tachycardia, fatigue, headache,
decreased appetite, chills, diarrhea, febrile neutropenia,
infections-pathogen unspecified, nausea, hypoxia, tremor, cough,
vomiting, dizziness, constipation, and cardiac arrhythmias. Serious
adverse reactions occurred in 52% of patients. The most common
serious adverse reactions (> 2%) include encephalopathy, fever,
lung infection, febrile neutropenia, cardiac arrhythmia, cardiac
failure, urinary tract infection, renal insufficiency, aphasia,
cardiac arrest, Clostridium difficile infection, delirium,
hypotension, and hypoxia.
The most common (≥ 10%) Grade 3 or higher reactions include
febrile neutropenia, fever, CRS, encephalopathy,
infections-pathogen unspecified, hypotension, hypoxia and lung
infections.
U.S. Indication for
Yescarta
Yescarta is a CD19-directed genetically modified autologous T
cell immunotherapy indicated for the treatment of adult patients
with relapsed or refractory large B-cell lymphoma after two or more
lines of systemic therapy, including diffuse large B-cell lymphoma
(DLBCL) not otherwise specified, primary mediastinal large B-cell
lymphoma, high-grade B-cell lymphoma, and DLBCL arising from
follicular lymphoma.
Limitation of Use: Yescarta is not indicated for the treatment
of patients with primary central nervous system lymphoma.
About Kite
Kite, a Gilead Company, is a biopharmaceutical company based in
Santa Monica, California. Kite is engaged in the development of
innovative cancer immunotherapies. The company is focused on
chimeric antigen receptor and T cell receptor engineered cell
therapies. For more information on Kite, please visit
www.kitepharma.com.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that
discovers, develops and commercializes innovative therapeutics in
areas of unmet medical need. The company’s mission is to advance
the care of patients suffering from life-threatening diseases.
Gilead has operations in more than 30 countries worldwide, with
headquarters in Foster City, California.
Forward-Looking
Statement
This press release includes forward-looking statements, within
the meaning of the Private Securities Litigation Reform Act of 1995
that are subject to risks, uncertainties and other factors,
including the risk that future clinical trials involving Yescarta
may have unfavorable results. All statements other than statements
of historical fact are statements that could be deemed
forward-looking statements. Investors are cautioned that any such
forward-looking statements are not guarantees of future performance
and involve risks and uncertainties and are cautioned not to place
undue reliance on these forward-looking statements. Actual results
may differ materially from those currently anticipated due to a
number of risks and uncertainties. Risks and uncertainties that
could cause the actual results to differ from expectations
contemplated by forward-looking statements include risks and
uncertainties detailed from time to time in Gilead Sciences, Inc.’s
Quarterly Report on Form 10-Q for the quarter ended September 30,
2017 as filed with the Securities and Exchange Commission. All
forward-looking statements are based on information currently
available to Gilead and Kite, and Gilead and Kite assume no
obligation and disclaim any intent to update any such
forward-looking statements.
US Prescribing Information for Yescarta,
including BOXED WARNING and Medication Guide, is available
at www.yescarta.com.
For more information on Gilead Sciences,
please visit the company’s website at www.gilead.com, follow
Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.
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version on businesswire.com: http://www.businesswire.com/news/home/20180118005218/en/
Gilead SciencesInvestorsSung Lee, 650-524-7792orMediaNathan
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