-- In Three-Year Follow-up in Adults with
Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia, Tecartus
Shows High Rates of Durable Response (CR+CRi 71%) and a Median
Overall Survival of 26 Months --
Kite, a Gilead Company (Nasdaq: GILD), today announced the
three-year follow-up results from the pivotal ZUMA-3 study of the
CAR T-cell therapy Tecartus® (brexucabtagene autoleucel). Results
from the analysis showed a median overall survival (OS) of 26
months and demonstrated that responses remained durable in adults
with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R
B-ALL) with a consistent safety profile observed since the two-year
analysis. These findings were presented today during a poster
session at the 5th European CAR T-cell Meeting, taking place in
Rotterdam, the Netherlands.
“For adult patients living with ALL, there is a need for
therapeutic options that provide long-term responses,” said Bijal
Shah, MD, ZUMA-3 investigator and medical oncologist, Moffitt
Cancer Center, Tampa, Florida. “The continued durable response and
significant improvement in survival indicated by these new data can
potentially establish a new standard of care for adult patients
living with this aggressive form of leukemia.”
In the Phase 2 treated patient cohort (n=55) the median
follow-up was 38.8 months (range, 32.7-44.6). The OS rate at 36.0
months was 47.1% (95% CI, 32.7-60.2), with a median OS of 26.0
months among all treated Phase 2 patients (n=55) and 38.9 months in
patients with complete remission (CR) or complete remission with
incomplete hematologic recovery (CRi; n=39). Overall CR rate (CR +
CRi), CR, and subsequent allogeneic stem cell transplant (alloSCT)
rates remained unchanged since the prior data cut at 71%, 56%, and
20%, respectively. Median (95% CI) relapse-free survival (RFS)
censored and not censored at subsequent alloSCT were both 11.6
(2.7-20.5) and 11.7 months (2.8-20.5), respectively.
For patients treated at the pivotal dose in both Phase 1 and 2
(n=78), the median follow-up at data cutoff was 41.6 months (range,
32.7-70.3). Median (95% CI) DOR censored and not censored at
subsequent alloSCT was 18.6 (9.6-24.1) and 20.0 (10.3-24.1) months,
respectively. Median (95% CI) RFS were both 11.7 (6.1-20.5) months.
At data cutoff, 36% of patients (28) were still alive with a median
OS of 25.6 months (95% CI, 16.2-47.0) in all treated patients
(n=78). The proportion of pooled Phase 1 and 2 patients with Grade
≥3 AEs that were deemed treatment-related was unchanged since the
prior data cut. No Grade 5 AEs occurred since the prior data cut
off.
“We are encouraged by the sustained benefit that a single
one-time treatment of Tecartus continues to provide for patients
living with this difficult-to-treat blood cancer,” said Frank
Neumann, MD, PhD, SVP, Kite’s Global Head of Clinical Development.
“Our hope is that these results, along with our commitment to
long-term research of Tecartus, will continue to provide clarity to
physicians on optimal treatment methods for these patients living
with this rare disease who have suffered historically poor
outcomes.”
In this trial, longer follow-up of the pivotal analysis and
outcomes of a larger pooled analysis of Phase 1 and 2 patients who
received the pivotal dose of Tecartus were reported. Most patients
in the analysis were heavily pre-treated, with a median of two
prior therapies, and 47% had received three or more prior
therapies.
About ZUMA-3
ZUMA-3 is an ongoing international multicenter (US, Canada,
Europe), single arm, open label, registrational Phase 1/2 study of
Tecartus in adult patients (≥18 years old) with ALL whose disease
is refractory to or has relapsed following standard systemic
therapy or hematopoietic stem cell transplantation. The primary
endpoint is the rate of overall complete remission or complete
remission with incomplete hematological recovery by central
assessment. Duration of remission and relapse-free survival,
overall survival, minimal residual disease (MRD) negativity rate,
and alloSCT rate were assessed as secondary endpoints.
About Acute Lymphoblastic
Leukemia
ALL is an aggressive and rare type of blood cancer that can also
involve the lymph nodes, spleen, liver, central nervous system and
other organs. While 80% of ALL occurs in children, it represents a
devastating disease in adults. In adults, B-cell precursor ALL is
the most common form, accounting for 75% of cases. Survival rates
in adults with R/R B-ALL are poor, with median OS at less than
eight months.
About Tecartus
Please see full FDA Prescribing Information, including BOXED
WARNING and Medication Guide.
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.
- Adult patients with relapsed or refractory B-cell precursor
acute lymphoblastic leukemia (ALL).
U.S. 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. CRS occurred in 92% (72/78) of patients with ALL,
including ≥ Grade 3 (Lee grading system) CRS in 26% of patients.
Three patients with ALL had ongoing CRS events at the time of
death. The median time to onset of CRS was five days (range: 1 to
12 days) and the median duration of CRS was eight days (range: 2 to
63 days) for patients with ALL.
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 Events, including those that were fatal or
life-threatening, occurred following treatment with Tecartus.
Neurologic events occurred in 87% (68/78) of patients with ALL,
including ≥ Grade 3 in 35% of patients. The median time to onset
for neurologic events was seven days (range: 1 to 51 days) with a
median duration of 15 days (range: 1 to 397 days) in patients with
ALL. For patients with MCL, 54 (66%) patients experienced CRS
before 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.
Neurologic events resolved for 119 out of 134 (89%) patients
treated with Tecartus. Nine patients (three patients with MCL and
six patients with ALL) had ongoing neurologic events at the time of
death. For patients with ALL, neurologic events occurred before,
during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of patients;
respectively. Three patients (4%) had neurologic events without
CRS. The onset of neurologic events can be concurrent with CRS,
following resolution of CRS or in the absence of CRS.
The most common neurologic events (>10%) were similar in MCL
and ALL and included encephalopathy (57%), headache (37%), tremor
(34%), confusional state (26%), aphasia (23%), delirium (17%),
dizziness (15%), anxiety (14%), and agitation (12%). Serious events
including encephalopathy, aphasia, confusional state, and seizures
occurred after treatment with Tecartus.
Monitor patients daily for at least seven days for patients with
MCL and at least 14 days for patients with ALL 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. Infections (all
grades) occurred in 56% (46/82) of patients with MCL and 44%
(34/78) of patients with ALL. Grade 3 or higher infections,
including bacterial, viral, and fungal infections, occurred in 30%
of patients with ALL and MCL. Tecartus should not be administered
to patients with clinically significant active systemic infections.
Monitor patients for signs and symptoms of infection before and
after Tecartus infusion and treat appropriately. Administer
prophylactic antimicrobials according to local guidelines.
Febrile neutropenia was observed in 6% of patients with MCL and
35% of patients with ALL after Tecartus infusion and may be
concurrent with CRS. The febrile neutropenia in 27 (35%) of
patients with ALL includes events of “febrile neutropenia” (11
(14%)) plus the concurrent events of “fever” and “neutropenia” (16
(21%)). 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, life-threatening and fatal
opportunistic infections have been reported. The possibility of
rare infectious etiologies (e.g., fungal and viral infections such
as HHV-6 and progressive multifocal leukoencephalopathy) should be
considered in 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 Tecartus
infusion. In patients with MCL, Grade 3 or higher cytopenias not
resolved by Day 30 following Tecartus infusion occurred in 55%
(45/82) of patients and included thrombocytopenia (38%),
neutropenia (37%), and anemia (17%). In patients with ALL who were
responders to Tecartus treatment, Grade 3 or higher cytopenias not
resolved by Day 30 following Tecartus infusion occurred in 20%
(7/35) of the patients and included neutropenia (12%) and
thrombocytopenia (12%); Grade 3 or higher cytopenias not resolved
by Day 60 following Tecartus infusion occurred in 11% (4/35) of the
patients and included neutropenia (9%) and thrombocytopenia (6%).
Monitor blood counts after Tecartus infusion.
Hypogammaglobulinemia: B cell aplasia and
hypogammaglobulinemia can occur in patients receiving treatment
with Tecartus. Hypogammaglobulinemia was reported in 16% (13/82) of
patients with MCL and 9% (7/78) of patients with ALL. 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 Tecartus
treatment, and until immune recovery following treatment with
Tecartus.
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 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 non-laboratory adverse
reactions (≥ 20%) were fever, cytokine release syndrome,
hypotension, encephalopathy, tachycardia, nausea, chills, headache,
fatigue, febrile neutropenia, diarrhea, musculoskeletal pain,
hypoxia, rash, edema, tremor, infection with pathogen unspecified,
constipation, decreased appetite, and vomiting. The most common
serious adverse reactions (≥ 2%) were cytokine release syndrome,
febrile neutropenia, hypotension, encephalopathy, fever, infection
with pathogen unspecified, hypoxia, tachycardia, bacterial
infections, respiratory failure, seizure, diarrhea, dyspnea, fungal
infections, viral infections, coagulopathy, delirium, fatigue,
hemophagocytic lymphohistiocytosis, musculoskeletal pain, edema,
and paraparesis.
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, focused on cell therapy to treat
and potentially cure cancer. As the global cell therapy leader,
Kite has treated more patients with CAR T-cell therapy than any
other company. Kite has the largest in-house cell therapy
manufacturing network in the world, spanning process development,
vector manufacturing, clinical trial production and commercial
product manufacturing. 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.
Gilead Sciences acquired Kite in 2017.
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 Gilead and Kite’s ability to initiate, progress or
complete clinical trials within currently anticipated timelines or
at all, and the possibility of unfavorable results from ongoing or
additional clinical trials, including those involving Tecartus; the
risk that physicians and patients may not see the potential
benefits of Tecartus for the treatment of adult patients with
relapsed or refractory B-cell ALL; and any assumptions underlying
any of the foregoing. 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 September 30, 2022, 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 Tecartus
including BOXED WARNING, is available at www.kitepharma.com
and www.gilead.com.
Kite, the Kite logo, Tecartus 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/20230209005227/en/
Jacquie Ross, Investors investor_relations@gilead.com
Anna Padula, Kite Media apadula@kitepharma.com
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