-- Landmark ZUMA-7 Study was Initiated
in 2017 as the First Randomized Clinical Trial to Test the Earlier
Use of a CAR T-cell Therapy Against Standard of Care --
-- Study Met the Primary and Key
Secondary Endpoints of Event-Free Survival and Objective Response
Rate, Demonstrating a Highly Statistically and Clinically
Significant Improvement Compared to Standard of Care --
Kite, a Gilead Company (Nasdaq: GILD), today announced top-line
results from the primary analysis of ZUMA-7, a randomized Phase 3
global, multicenter study showing superiority of Yescarta®
(axicabtagene ciloleucel) compared to standard of care (SOC) in
second-line relapsed or refractory large B-cell lymphoma (LBCL).
With a median follow-up of two years, the study met the primary
endpoint of event-free survival (EFS; hazard ratio 0.398, p
<0.0001). The study also met the key secondary endpoint of
objective response rate (ORR). The interim analysis of overall
survival (OS) showed a trend favoring Yescarta; however, the data
are immature at this time, and further analyses are planned for the
future.
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Kite Pharma ZUMA-7 Global Clinical Trial
Sites Map - Centers
Overall survival measures deaths over time from any cause.
Event-free survival is defined as time from randomization to
disease progression, commencement of new lymphoma therapy, or death
from any cause. ZUMA-7 was conducted under a Special Protocol
Agreement (SPA) with the U.S. Food and Drug Administration (FDA)
whereby the trial design, clinical endpoints and statistical
analysis were agreed in advance with the Agency.
Safety results from the study were consistent with or lower than
the known safety profile of Yescarta for the treatment of LBCL in
the third-line setting. Six percent of patients experienced
cytokine release syndrome (CRS) Grade 3 or higher, with a median
onset of three days, and 21% experienced neurological events Grade
3 or higher. No new safety concerns were identified in this
second-line setting.
“The top-line results of the randomized ZUMA-7 trial paint the
picture of a potential paradigm shift in the treatment of large
B-cell lymphoma,” said Frederick L. Locke, MD, ZUMA-7 Lead
Principal Investigator and Co-Leader of the Immuno-Oncology Program
at Moffitt Cancer Center, Tampa, Florida. “The outcomes for
patients relapsing after frontline chemotherapy in this study are
dramatically improved with rapid referral (to a CAR T center) and a
single infusion of axicabtagene ciloleucel as compared to
chemotherapy and consolidative autologous transplant, the
longstanding second-line standard of care.”
ZUMA-7 evaluated an one-time infusion of the CAR T-cell therapy
Yescarta compared to SOC in adult patients with relapsed or
refractory LBCL. Standard of care for relapsed or refractory LBCL
is a two-step process: immunochemotherapy is reintroduced, and if
the patient responds and can tolerate further treatment, they move
on to high-dose chemotherapy plus stem cell transplant.
“Yescarta has been instrumental in transforming outcomes for
patients with third-line LBCL. Our goal has always been to bring
the benefit of CAR T-cell therapy to more patients, earlier in
their treatment, where the potential for benefit may be even
greater,” said Christi Shaw, Chief Executive Officer of Kite. “As
the leader in cell therapy, Kite is honored to deliver this
landmark study and would like to thank the patients, families,
physicians and care teams around the world that made this
possible.”
ZUMA-7 was initiated in 2017 and enrolled 359 patients in 77
centers around the world. Results released today represent the
longest follow-up time of any study in this setting with two years
median follow-up. Patients enrolled in the study ranged in age from
22 to 81, with 30% of the patients 65 or older.
“Over 40 years ago, we learned the important role T-cells play
in fighting cancer, and 20 years ago autologous stem cell
transplant became an option to treat lymphoma. Today's results show
us the potential power of cell therapy for patients with lymphoma
when used earlier, and instead of standard treatment options,” said
Frank Neumann, MD, PhD, Kite’s Global Head of Clinical
Development.
Detailed results from ZUMA-7 will be submitted for presentation
at a future medical congress, and Kite plans to initiate
discussions with the U.S. Food and Drug Administration, European
Medicines Agency and other global health authorities regarding
submission of a supplemental Biologics License Application later
this year to expand the currently approved indications for
Yescarta. See About Yescarta section for current Yescarta approved
indications. Yescarta has not been approved by any regulatory
agency for the treatment of patients in the second-line setting
similar to those in ZUMA-7.
About 40% of patients with LBCL will need second-line treatment,
as their cancer will either relapse (return) or become refractory
(not respond) to treatment.
About ZUMA-7 Study
Design
ZUMA-7 is a randomized, open-label, global, multicenter, Phase 3
study evaluating the safety and efficacy of Yescarta versus current
standard of care (SOC) for second-line therapy (platinum-based
salvage combination chemotherapy regimen followed by high-dose
therapy and autologous stem cell transplant in those who respond to
salvage chemotherapy) in adult patients with relapsed or refractory
(within or equal to 12 months of first-line therapy), large B-cell
lymphoma (LBCL). In the study, 359 patients were randomized (1:1)
to receive a single infusion of Yescarta or current SOC second-line
therapy. The primary endpoint is event-free survival (EFS), defined
as the time from randomization to the earliest date of disease
progression per Lugano Classification (Cheson et al, 2014),
commencement of new lymphoma therapy, or death from any cause as
determined by blinded central review. Key secondary endpoints
include objective response rate (ORR) and overall survival (OS).
Other secondary endpoints include modified EFS, progression-free
survival (PFS) and duration of response (DOR).
About 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. Limitations of Use: Yescarta is not indicated for
the treatment of patients with primary central nervous system
lymphoma.
- Adult patients with relapsed or refractory follicular lymphoma
(FL) after two or more lines of systemic therapy. This indication
is approved under accelerated approval based on response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trial(s).
U.S. IMPORTANT SAFETY
INFORMATION
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 and Tecartus REMS Program.
CYTOKINE RELEASE SYNDROME (CRS), including fatal or
life-threatening reactions, occurred. CRS occurred in 88% (224/254)
of all patients with non-Hodgkin lymphoma (NHL), including Grade ≥3
in 10%. CRS occurred in 94% (101/108) of patients with large B-cell
lymphoma (LBCL), including Grade ≥3 in 13%. Among patients with
LBCL who died after receiving Yescarta, 4 had ongoing CRS events at
the time of death. The median time to onset of CRS was 2 days
(range: 1-12 days) and the median duration was 7 days (range: 2-58
days) for patients with LBCL. CRS occurred in 84% (123/146) of
patients with indolent non-Hodgkin lymphoma (iNHL), including Grade
≥3 in 8% (11/146). Among patients with iNHL who died after
receiving Yescarta, 1 patient had an ongoing CRS event at the time
of death. The median time to onset of CRS was 4 days (range: 1-20
days) and median duration was 6 days (range: 1-27 days) for
patients with iNHL. Key manifestations of CRS (≥10%) in all
patients combined included fever (80%), hypotension (38%),
tachycardia (29%), hypoxia (21%), chills (21%), and headache (13%).
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, multi-organ failure
and hemophagocytic lymphohistiocytosis/macrophage activation
syndrome. In a subsequent cohort of LBCL patients, tocilizumab
and/or corticosteroids were administered for ongoing Grade 1
events. CRS occurred in 93% (38/41) of these patients and 2% (1/41)
had Grade 3 CRS, with no patients experiencing a Grade 4 or 5
event. The median time to onset of CRS was 2 days (range: 1 to 8
days) and the median duration of CRS was 7 days (range: 2 to 16
days). Key manifestations of CRS (>5%) included pyrexia,
hypotension, chills, headache, nausea, tachycardia, C-reactive
protein increased, fatigue, hypoxia, and vomiting. Ensure that 2
doses of tocilizumab are available prior to Yescarta infusion.
Following infusion, monitor patients for signs and symptoms of CRS
at least daily for 7 days at the certified healthcare facility, and
for 4 weeks thereafter. 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 that were fatal or life-threatening
occurred. Neurologic toxicities occurred in 81% (206/254) of all
patients with NHL receiving Yescarta, including Grade ≥3 in 26%.
Neurologic toxicities occurred in 87% (94/108) of patients with
LBCL, including Grade ≥3 in 31%. The median time to onset was 4
days (range: 1-43 days) and the median duration was 17 days for
patients with LBCL. Neurologic toxicities occurred in 77% (112/146)
of patients with iNHL, including Grade ≥3 in 21%. The median time
to onset was 6 days (range: 1-79 days) and the median duration was
16 days for patients with iNHL. 98% of all neurologic toxicities in
patients with LBCL and 99% of all neurologic toxicities in patients
with iNHL occurred within the first 8 weeks of Yescarta infusion.
Neurologic toxicities occurred within the first 7 days of infusion
for 89% of affected patients with LBCL and 74% of affected patients
with iNHL. The most common neurologic toxicities (≥10%) in all
patients combined included encephalopathy (53%), headache (45%),
tremor (31%), dizziness (20%), delirium (16%), aphasia (15%), and
insomnia (11%). Prolonged encephalopathy lasting up to 173 days was
noted. Serious events, including leukoencephalopathy and seizures,
as well as fatal and serious cases of cerebral edema, have
occurred. In a subsequent cohort of LBCL patients who received
corticosteroids at the onset of Grade 1 toxicities, neurologic
toxicities occurred in 78% (32/41) of these patients and 20% (8/41)
had Grade 3 neurologic toxicities with no patients experiencing a
Grade 4 or 5 event. The median time to onset of neurologic
toxicities was 6 days (range: 1-93 days) with a median duration of
8 days (range: 1-144 days). The most common neurologic toxicities
were consistent with the overall LBCL population treated with
Yescarta. Following Yescarta infusion, monitor patients for signs
and symptoms of neurologic toxicities at least daily for 7 days at
the certified healthcare facility, and for 4 weeks thereafter, and
treat promptly.
REMS: Because of the risk of CRS and neurologic
toxicities, Yescarta is available only through a restricted program
called the Yescarta and Tecartus REMS Program which requires that:
Healthcare facilities that dispense and administer Yescarta must be
enrolled and comply with the REMS requirements and must have
on-site, immediate access to a minimum of 2 doses of tocilizumab
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.YescartaTecartusREMS.com or 1-844-454-KITE (5483).
HYPERSENSITIVITY REACTIONS: Allergic reactions, including
serious hypersensitivity reactions or anaphylaxis, may occur with
the infusion of Yescarta.
SERIOUS INFECTIONS: Severe or life-threatening infections
occurred. Infections (all grades) occurred in 47% (119/254) of all
patients with NHL. Grade ≥3 infections occurred in 19% of patients,
Grade ≥3 infections with an unspecified pathogen occurred in 15%,
bacterial infections in 5%, viral infections in 2%, and fungal
infections in 1%. Yescarta should not be administered to patients
with clinically significant active systemic infections. Monitor
patients for signs and symptoms of infection before and after
infusion and treat appropriately. Administer prophylactic
anti-microbials according to local guidelines. Febrile neutropenia
was observed in 40% of all patients with NHL 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. In immunosuppressed
patients, including those who have received Yescarta,
life-threatening and fatal opportunistic infections including
disseminated fungal infections (e.g., candida sepsis and
aspergillus infections) and viral reactivation (e.g., human herpes
virus-6 [HHV-6] encephalitis and JC virus progressive multifocal
leukoencephalopathy [PML]) have been reported. The possibility of
HHV-6 encephalitis and PML should be considered in immunosuppressed
patients with neurologic events and appropriate diagnostic
evaluations should be performed. 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. Grade ≥3 cytopenias not resolved by Day 30 following
Yescarta infusion occurred in 30% of all patients with NHL and
included neutropenia (22%), thrombocytopenia (13%), and anemia
(5%). Monitor blood counts after infusion.
HYPOGAMMAGLOBULINEMIA and B-cell aplasia can occur.
Hypogammaglobulinemia occurred in 17% of all patients with NHL.
Monitor immunoglobulin levels after treatment 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.
SECONDARY MALIGNANCIES may develop. Monitor life-long for
secondary malignancies. In the event that one 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 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%) in patients with LBCL included CRS, fever,
hypotension, encephalopathy, tachycardia, fatigue, headache,
decreased appetite, chills, diarrhea, febrile neutropenia,
infections with pathogen unspecified, nausea, hypoxia, tremor,
cough, vomiting, dizziness, constipation, and cardiac arrhythmias.
The most common non-laboratory adverse reactions (incidence ≥20%)
in patients with iNHL included fever, CRS, hypotension,
encephalopathy, fatigue, headache, infections with pathogen
unspecified, tachycardia, febrile neutropenia, musculoskeletal
pain, nausea, tremor, chills, diarrhea, constipation, decreased
appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness.
Please see full Prescribing Information, including BOXED
WARNING and Medication Guide.
About Kite
Kite, a Gilead Company, is a global biopharmaceutical company
based in Santa Monica, California, with commercial manufacturing
operations in North America and Europe. Kite’s singular focus is
cell therapy to treat and potentially cure cancer. As the cell
therapy leader, Kite has more approved CAR T indications to help
more patients than any other company. For more information on Kite,
please visit www.kitepharma.com.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has
pursued and achieved breakthroughs in medicine for more than three
decades, with the goal of creating a healthier world for all
people. The company is committed to advancing innovative medicines
to prevent and treat life-threatening diseases, including HIV,
viral hepatitis and cancer. Gilead operates in more than 35
countries worldwide, with headquarters in Foster City,
California.
Forward-Looking
Statements
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 possibility of unfavorable results from ongoing and
additional clinical trials involving Yescarta. These and other
risks, uncertainties and other factors are described in detail in
Gilead’s Quarterly Report on Form 10-Q for the quarter ended March
31, 2021, as filed with the U.S. Securities and Exchange
Commission. These risks, uncertainties and other factors could
cause actual results to differ materially from those referred to in
the forward-looking statements. 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. All
forward-looking statements are based on information currently
available to Kite and Gilead, and Kite and Gilead assume no
obligation and disclaim any intent to update any such
forward-looking statements.
U.S. Prescribing Information for Yescarta
including BOXED WARNING, is available at www.kitepharma.com
and www.gilead.com.
Kite, the Kite logo, Yescarta, Tecartus, XLP
and GILEAD are trademarks of Gilead Sciences, Inc. or its related
companies.
For more information on Kite, please visit the
company’s website at www.kitepharma.com or call Gilead Public
Affairs at 1-800-GILEAD-5 or 1-650-574-3000. Follow Kite on social
media on Twitter (@KitePharma) and LinkedIn.
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version on businesswire.com: https://www.businesswire.com/news/home/20210628005449/en/
Jacquie Ross, Investors (650) 358-1054
Mary Lynn Carver, Media (410) 443-1853
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