-- Median Overall Survival Still Not Reached
After Single Infusion of Tecartus in Pivotal ZUMA-2 Trial
--
-- Significant and Durable Rate of Complete
Response Further Supports Tecartus as First and Only CAR T-Cell
Therapy in Relapsed or Refractory MCL --
Kite, a Gilead Company (Nasdaq: GILD), today announced follow-up
results from the pivotal ZUMA-2 trial of Tecartus™ (brexucabtagene
autoleucel, formerly KTE-X19) in adult patients with relapsed or
refractory mantle cell lymphoma (MCL). At a median follow-up of
17.5 months (n=60 evaluable for efficacy), 92 percent of patients
had achieved a response, including 67 percent with a complete
response (CR). Secondary endpoints of median duration of response,
progression-free survival (PFS) and overall survival (OS) all were
not yet reached. These data were presented at the 62nd ASH Annual
Meeting and Exposition (Abstract #1120).
“Patients with mantle cell lymphoma face a disease that often
becomes more aggressive over time and nearly always relapses after
initial therapy,” said Michael Wang, MD, Puddin Clarke Endowed
Professor, Department of Lymphoma and Myeloma at The University of
Texas MD Anderson Cancer Center. “Many patients with relapsed or
refractory MCL will have high-risk disease that is more likely to
keep progressing after treatment, so our goal with any therapy is
to provide durable remission. With more than half of the patients
in the ZUMA-2 trial still alive at nearly one and a half years
after infusion, these results reinforce brexucabtagene autoleucel’s
potential to address the gap in existing treatment.”
Among all efficacy-evaluable patients (n=60), 48 percent had
ongoing responses at data cut-off. Estimates for PFS and OS at 15
months were 59 percent and 76 percent, respectively. The first 28
patients treated had a median follow-up of 32.3 months, and 39
percent of these patients remain in remission with no further
therapy.
Among all patients (n=68), Grade 3 or higher cytokine release
syndrome (CRS) and neurologic events (NE) occurred in 15 percent
and 31 percent of patients, respectively. No new Grade 5 events
occurred with additional follow-up.
“These Tecartus data build on the significant response rates
seen previously with an impressive durability, which continues to
show that we have a potentially transformative treatment option for
patients with relapsed or refractory MCL,” said Ken Takeshita, MD,
Kite’s Global Head of Clinical Development. “As we continue to
observe longer-term results with Tecartus, as well as with the most
recent four-year results for Yescarta, our first CAR T-cell
therapy, we are encouraged by the unparalleled long-term survival
benefits that may be possible with these cell therapies.”
In July, Tecartus became the first CAR T-cell therapy to receive
accelerated approval from the FDA for the treatment of relapsed or
refractory mantle cell lymphoma, based on overall response rate and
durability of response. Continued approval for this indication may
be contingent upon additional data from a confirmatory trial. The
Tecartus U.S. Prescribing Information has a Boxed Warning in its
product label regarding the risks of CRS and neurologic toxicities,
and Tecartus is approved with a risk evaluation and mitigation
strategy (REMS) due to these risks; see below for Indication and
Important Safety Information.
About Mantle Cell
Lymphoma
MCL is a rare form of non-Hodgkin lymphoma (NHL) that arises
from cells originating in the “mantle zone” of the lymph node and
predominantly affects men over the age of 60. MCL is highly
aggressive following relapse, with many patients progressing
following therapy.
About ZUMA-2
ZUMA-2 is an ongoing, single arm, open-label trial that enrolled
74 adult patients with relapsed or refractory MCL who had
previously received anthracycline- or bendamustine-containing
chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine
kinase inhibitor (ibrutinib or acalabrutinib). The primary endpoint
is objective response rate (ORR) per the Lugano Classification
(2014), defined as the combined rate of CR and partial responses as
assessed by an Independent Radiologic Review Committee (IRRC).
About Tecartus
Tecartus is an autologous, anti-CD19 CAR T cell therapy.
Tecartus uses the XLP™ manufacturing process that includes T cell
enrichment, a necessary step in certain B-cell malignancies in
which circulating lymphoblasts are a common feature. In addition to
MCL, Tecartus is also currently in Phase 1/2 trials in acute
lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia
(CLL). The use of Tecartus in ALL and CLL is investigational, and
its safety and efficacy have not been established in these cancer
types.
Tecartus Indication
Tecartus is a CD19-directed genetically modified autologous T
cell immunotherapy indicated for the treatment of adult patients
with relapsed or refractory mantle cell lymphoma (MCL).
This indication is approved under accelerated approval based on
overall response rate and durability of response. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in a confirmatory trial.
IMPORTANT SAFETY
INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC
TOXICITIES
- Cytokine Release Syndrome (CRS), including life-threatening
reactions, occurred in patients receiving Tecartus. Do not
administer Tecartus to patients with active infection or
inflammatory disorders. Treat severe or life-threatening CRS with
tocilizumab or tocilizumab and corticosteroids.
- Neurologic toxicities, including life-threatening reactions,
occurred in patients receiving Tecartus, including concurrently
with CRS or after CRS resolution. Monitor for neurologic toxicities
after treatment with Tecartus. Provide supportive care and/or
corticosteroids as needed.
- Tecartus 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
life-threatening reactions, occurred following treatment with
Tecartus. In ZUMA-2, CRS occurred in 91% (75/82) of patients
receiving Tecartus, including ≥ Grade 3 CRS in 18% of patients.
Among the patients who died after receiving Tecartus, one had a
fatal CRS event. The median time to onset of CRS was three days
(range: 1 to 13 days) and the median duration of CRS was ten days
(range: 1 to 50 days). Among patients with CRS, key manifestations
(>10%) included fever (99%), hypotension (60%), hypoxia (37%),
chills (33%), tachycardia (37%), headache (24%), fatigue (19%),
nausea (13%), alanine aminotransferase increased (13%), aspartate
aminotransferase increased (12%), and diarrhea (11%). Serious
events associated with CRS included hypotension, fever, hypoxia,
acute kidney injury, and tachycardia.
Ensure that a minimum of two doses of tocilizumab are available
for each patient prior to infusion of Tecartus. Following infusion,
monitor patients for signs and symptoms of CRS daily for at least
seven days at the certified healthcare facility, and for four 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, including those that were
life-threatening, occurred following treatment with Tecartus. In
ZUMA-2, neurologic events occurred in 81% of patients, 37% of whom
experienced Grade ≥3 adverse reactions. The median time to onset
for neurologic events was six days (range: 1 to 32 days).
Neurologic events resolved for 52 out of 66 (79%) patients with a
median duration of 21 days (range: 2 to 454 days). Three patients
had ongoing neurologic events at the time of death, including one
patient with serious encephalopathy. The remaining unresolved
neurologic events were either Grade 1 or Grade 2. Fifty-four (66%)
patients experienced CRS by the onset of neurological events. Five
(6%) patients did not experience CRS with neurologic events and
eight patients (10%) developed neurological events after the
resolution of CRS. 85% of all treated patients experienced the
first CRS or neurological event within the first seven days after
Tecartus infusion.
The most common neurologic events (>10%) included
encephalopathy (51%), headache (35%), tremor (38%), aphasia (23%),
and delirium (16%). Serious events including encephalopathy,
aphasia, and seizures occurred.
Monitor patients daily for at least seven days at the certified
healthcare facility and for four weeks following infusion for signs
and symptoms of neurologic toxicities and treat promptly.
REMS Program: Because of the risk of CRS and neurologic
toxicities, Tecartus is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the
Yescarta and Tecartus REMS Program which requires that:
- Healthcare facilities that dispense and administer Tecartus
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 two hours after
Tecartus infusion, if needed for treatment of CRS.
- Certified healthcare facilities must ensure that healthcare
providers who prescribe, dispense, or administer Tecartus are
trained in the management of CRS and neurologic toxicities. Further
information is available at www.YescartaTecartusREMS.com or
1-844-454-KITE (5483).
Hypersensitivity Reactions: Serious hypersensitivity
reactions, including anaphylaxis, may occur due to dimethyl
sulfoxide (DMSO) or residual gentamicin in Tecartus.
Severe Infections: Severe or life-threatening infections
occurred in patients after Tecartus infusion. In ZUMA-2, infections
(all grades) occurred in 56% of patients. Grade 3 or higher
infections, including bacterial, viral, and fungal infections,
occurred in 30% of patients. Tecartus 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
antimicrobials according to local guidelines.
Febrile neutropenia was observed in 6% of patients after
Tecartus 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 Tecartus
infusion. In ZUMA-2, Grade ≥3 cytopenias not resolved by Day 30
following Tecartus infusion occurred in 55% of patients and
included thrombocytopenia (38%), neutropenia (37%), and anemia
(17%). Monitor blood counts after infusion.
Hypogammaglobulinemia and B-cell aplasia can occur in
patients receiving treatment with Tecartus. In ZUMA-2,
hypogammaglobulinemia occurred in 16% of patients. Monitor
immunoglobulin levels after treatment with Tecartus and manage
using infection precautions, antibiotic prophylaxis, and
immunoglobulin replacement. The safety of immunization with live
viral vaccines during or following Tecartus treatment has not been
studied. Vaccination with live virus vaccines is not recommended
for at least six weeks prior to the start of lymphodepleting
chemotherapy, during treatment, and until immune recovery following
treatment with Tecartus.
Secondary Malignancies may develop. Monitor life-long for
secondary malignancies. In the event that it 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 Tecartus
infusion. Advise patients to refrain from driving and engaging in
hazardous activities, such as operating heavy or potentially
dangerous machinery, during this period.
Adverse Reactions: The most common adverse reactions
(incidence ≥ 20%) were pyrexia, CRS, hypotension, encephalopathy,
fatigue, tachycardia, arrhythmia, infection – pathogen unspecified,
chills, hypoxia, cough, tremor, musculoskeletal pain, headache,
nausea, edema, motor dysfunction, constipation, diarrhea, decreased
appetite, dyspnea, rash, insomnia, pleural effusion, and aphasia.
Serious adverse reactions occurred in 66% of patients. The most
common serious adverse reactions (> 2%) were encephalopathy,
pyrexia, infection – pathogen unspecified, CRS, hypoxia, aphasia,
renal insufficiency, pleural effusion, respiratory failure,
bacterial infections, dyspnea, fatigue, arrhythmia, tachycardia,
and viral infections.
Please see full Prescribing Information, including BOXED
WARNING and Medication Guide.
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 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.
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 and Tecartus REMS Program.
CYTOKINE RELEASE SYNDROME (CRS) occurred in 94% of
patients, with 13% ≥ Grade 3. Among patients who died after
receiving Yescarta, 4 had ongoing CRS at death. The median time to
onset was 2 days (range: 1-12 days) and median duration was 7 days
(range: 2-58 days). Key manifestations 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 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 occurred in 87% of patients, 98% of
which occurred within the first 8 weeks with a median time to onset
of 4 days (range: 1-43 days) and a median duration of 17 days.
Grade ≥3 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, as well as fatal and serious cases of cerebral edema have
occurred. 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 38% of patients.
Grade ≥3 infections occurred in 23% of patients; those due to 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 infusion and treat appropriately.
Administer prophylactic anti-microbials according to local
guidelines. Febrile neutropenia was observed in 36% of patients 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. 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 28% of patients and included
thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor
blood counts after infusion.
HYPOGAMMAGLOBULINEMIA and B-cell aplasia can occur.
Hypogammaglobulinemia occurred in 15% of patients. 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 (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.
Please see full Prescribing Information, including BOXED
WARNING and Medication Guide.
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, Inc. is a research-based biopharmaceutical
company that discovers, develops and commercializes innovative
medicines in areas of unmet medical need. The company strives to
transform and simplify care for people with life-threatening
illnesses around the world. Gilead has operations in more than 35
countries worldwide, with headquarters in Foster City, California.
For more information on Gilead Sciences, please visit the company’s
website at www.gilead.com.
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 physicians and patients may not see the
potential benefits of Tecartus therapy and the possibility of
unfavorable results from other ongoing and additional clinical
studies involving Tecartus for the treatment of adult patients with
relapsed or refractory MCL and other potential indications. There
is also the risk that the European Commission may not approve
KTE-X19 for the treatment of relapsed or refractory MCL in the
anticipated timelines or at all, and the marketing approval, if
granted, may have significant limitations on its use. All
statements other than statements of historical fact are statements
that could be deemed forward-looking statements. These risks,
uncertainties and other factors could cause actual results to
differ materially from those referred to in the forward-looking
statements. The reader is cautioned not to rely on these
forward-looking statements. These and other risks are described in
detail in Gilead’s Quarterly Report on Form 10-Q for the quarter
ended September 30, 2020, as filed with the U.S. 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 to update any such forward-looking
statements.
U.S. Prescribing Information for Tecartus and
Yescarta, including BOXED WARNINGS, 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/20201205005004/en/
Douglas Maffei, PhD, Investors (650) 522-2739
Nathan Kaiser, Media (650) 522-1853
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