Market Overview

Kite Announces Clinical Collaboration to Evaluate Investigational Combination of Yescarta™ (Axicabtagene Ciloleucel) and Pfizer's Utomilumab in Large B-Cell Lymphoma


-- 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.

This press release features multimedia. View the full release here:

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

The combination of Yescarta and utomilumab is investigational and has
not been proven safe and effective.

U.S. Important Safety Information for Yescarta


  • 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

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

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
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


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
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

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

For more information on Gilead Sciences, please visit the company's
website at,
follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.

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