– At Almost Four Years of Follow-up in the
Pivotal ZUMA-2 Study, Median Overall Survival was 46.4 Months,
Supporting Long-Term Response in Adult Patients with
Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) –
– Real-World Evidence (RWE) Shows
Effectiveness in Adult R/R MCL with a Complete Response Rate of 81%
and 84% for High-Risk Features (Patients with TP53 /17p Deletion)
–
– RWE Also Shows a Complete Remission/CRi
Rate of 76% in Adult Patients with R/R B-Cell Precursor Acute
Lymphoblastic Leukemia (B-ALL) –
Kite, a Gilead Company (Nasdaq: GILD), today announced the
results of four new analyses supporting the use of Tecartus®
(brexucabtagene autoleucel) in relapsed/refractory mantle cell
lymphoma (R/R MCL) and relapsed/refractory adult B-cell precursor
acute lymphoblastic leukemia (R/R B-ALL). These results include
four-year overall survival (OS) data from the pivotal ZUMA-2 study
and primary results from ZUMA-18, an expanded access study,
evaluating the CAR T-cell therapy Tecartus in patients with R/R MCL
that were presented orally (Abstract #106) at the 2023 American
Society of Hematology (ASH) Annual Meeting & Exposition.
An analysis from ZUMA-2 showing that patients who received early
versus late intervention for management of cytokine release
syndrome (CRS) and neurological events experienced improved safety
outcomes was also presented in a poster session (Abstract
#2120).
In addition, real-world findings on effectiveness and safety
outcomes from the Center for International Blood and Marrow
Transplant Research (CIBMTR) observational database of U.S.
patients who received Tecartus for R/R MCL (Abstract #107) were
highlighted in an oral session; CIBMTR data from adult patients
with R/R B-ALL (Abstract #1029) were also presented orally
today.
“The clinical results and real-world evidence presented at ASH
clearly support the potential for long-term response and safety of
Tecartus in aggressive blood cancers for which patients have
limited treatment options,” said Frank Neumann, MD, PhD, Senior
Vice President, Global Head of Clinical Development, Kite. “We are
particularly encouraged that the real-world evidence demonstrates
consistent outcomes for Tecartus among a broader range of
patients.”
Detailed Information on Tecartus
Abstracts:
(Abstract #106)
Outcomes of Patients with Relapsed/Refractory Mantle Cell
Lymphoma (R/R MCL) Treated with Brexucabtagene Autoleucel
(Brexu-cel) in ZUMA-2 and ZUMA-18, an Expanded Access Study
At a median follow-up of 47.5 months in all 68 patients with R/R
MCL who had previously received anthracycline or
bendamustine-containing chemotherapy; an anti CD20 antibody; and a
Bruton’s tyrosine kinase inhibitor (BTKi; ibrutinib or
acalabrutinib); and were treated with Tecartus in the pivotal
ZUMA-2 study, median OS was 46.4 months with 30 patients (44%)
still alive at data cutoff. The median OS for patients with
complete response (CR) (n=46) was 58.7 months.
Efficacy and safety outcomes for 23 patients with R/R MCL
enrolled in ZUMA-18, a multicenter, open-label, expanded-access
study of Tecartus, were also presented. With a median follow-up of
33.5 months, the investigator-assessed objective response rate
(ORR) was 87% (95% Confidence Interval [CI], 66.4-97.2); 57% had a
CR (95% CI, 34.5-76.8), 30% had a partial response (95% CI,
13.2-52.9), and 9% had progressive disease (95% CI, 1.1-28.0) as
their best response to Tecartus. The median OS was not reached (95%
CI, 10.4-not estimable) at data cutoff with a 58% OS rate at 24
months.
At data cutoff, 61% of patients were still alive. All 23
patients who received Tecartus in ZUMA-18 experienced at least one
Grade ≥3 adverse event (AE); Grade ≥3 CRS and neurological events
occurred in one patient (4%) and eight patients (35%),
respectively. Five Grade 5 AEs occurred, one that was deemed
related to Tecartus therapy (multiple organ dysfunction syndrome on
Day 20) and four that were deemed unrelated to Tecartus therapy
(sepsis [2, Days 123 and 219], aspiration [1, on Day 49], and
encephalopathy [1, on Day 68]).
“Consistent with ZUMA-2 findings, which showed a median overall
survival of 46.4 months in patients with a complete response,
brexu-cel demonstrated a high level of efficacy in
relapsed/refractory mantle cell lymphoma patients in the ZUMA-18
expanded-access study, with less serious cytokine release
syndrome,” said Andre Goy, MD, ZUMA-2 investigator and Lymphoma
Division Chief, John Theurer Cancer Center, Hackensack University
Medical Center. “Together, the results of these two studies provide
strong support for the continued use of brexu-cel in the
relapsed/refractory mantle cell lymphoma setting.”
(Abstract #107)
Real-world Outcomes of Brexucabtagene Autoleucel (Brexu-cel) for
Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL): A CIBMTR
Subgroup Analysis of High-Risk Characteristics
Patients with R/R MCL and TP53 mutation/deletion or high Ki-67
proliferation index (PI) have historically had limited treatment
options with dismal outcomes. In a previously presented three-year
follow-up of ZUMA-2, outcomes were comparable across various
high-risk subgroups, including in patients with TP53 mutation or
Ki-67 PI ≥ 30% or ≥ 50%.
An analysis of a CIBMTR observational database of R/R MCL
patients receiving Tecartus from 84 U.S. centers was presented.
With a median follow-up of 12.2 months, CR rates were high among
these challenging-to-treat sub-populations:
- For patients with deletion of TP53/17p (n=44), CR was 84%
compared to 81% in those without (n=183)
- For patients with Ki-67 PI ≥ 50% (n=146), CR was 83% vs 84% in
those with Ki-67 PI < 50% (n=111).
Safety endpoints were largely consistent among all subgroups.
Prolonged neutropenia and thrombocytopenia occurred more frequently
in patients with vs without deletion of TP53/17p (25% vs 13% and
28% vs 16%, respectively). Grade ≥ 3 CRS occurred more frequently
in ZUMA-2-ineligible vs eligible patients (13% vs 7%). After
multivariable adjustment, all effectiveness and most safety
outcomes were consistent regardless of deletion of TP53/17p and
Ki-67 >+50%.
“These real-world findings suggest that outcomes of brexu-cel
treatment, including a high complete response rate, are largely
consistent, regardless of ZUMA-2 eligibility or the high-risk
feature subgroups analyzed. Although patients without deletion of
TP53/17p appeared to have longer overall survival than patients
with, the data further demonstrate the safety and durability of
response of brexu-cel for patients with relapsed/refractory mantle
cell lymphoma, who typically face poor prognoses and have limited
treatment options,” said Swetha Kambhampati, MD, lead investigator,
City of Hope assistant professor, Division of Lymphoma, Department
of Hematology & Hematopoietic Cell Transplantation.
(Abstract #1029)
Real-world outcomes of brexucabtagene autoleucel (brexu-cel) for
relapsed or refractory (R/R) adult B-cell acute lymphoblastic
leukemia (B-cell ALL): Evidence from the CIBMTR registry
This real-world evidence study of Tecartus in adult patients
with B-ALL examined a CIBMTR registry database of 150 patients
across 67 centers in the United States.
The assessment found the overall complete remission or complete
remission with incomplete hematological recovery (CR/CRi) rate by
Day 100 post-infusion was 76%, and 70% were still in remission at 6
months post-initial response (95% CI: 55-80). For those who were
not in response prior to lymphodepletion (LD), 63% of these
patients converted to a CR/CRi post-infusion.
The OS rate at six months was 78% (95% CI: 69-84); primary
causes of death were primary disease (n=13/32, 41%) and infection
(n=7/32, 22%). About one-third (31%) of responders received a
subsequent allogeneic stem cell transplant (allo SCT). High
response rates were observed in all patients regardless of age,
prior exposure to blinatumomab, prior allo SCT, or the presence of
extramedullary disease prior to LD. Grade ≥3 CRS and immune
effector cell-associated neurotoxicity syndrome (ICANS, ASTCT
consensus) occurred in 9% and 24% of patients, respectively.
Treatment for CRS and/or ICANS consisted mainly of tocilizumab
(67%) and corticosteroids (51%). Most of these AEs were resolved
within three weeks of infusion (CRS, 94%; ICANS, 80%). Prolonged
cytopenia and neutropenia 30 days post-infusion were experienced by
42% and 33% of patients, respectively.
“It is encouraging to see that the efficacy and safety outcomes
of the largest real-world evidence study of brexu-cel in B-ALL are
consistent with the results of the ZUMA-3 study, with high response
rates in a broad, actual patient population,” said Evandro Bezerra,
MD, lead investigator, hematology specialist, Ohio State University
Comprehensive Cancer Center. “These findings further build our
confidence in the role of brexu-cel in treating adult patients with
B-ALL, including those living with high-risk comorbidities and
other factors that make treatment particularly challenging.”
About ZUMA-2
ZUMA-2 is a single-arm, international multicenter (US and
Europe), open-label Phase 2 study involving 74
enrolled/leukapheresed adult patients (≥18 years old) with MCL
whose disease is refractory to or has relapsed following up to five
prior lines of therapy, including anthracycline or
bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody
therapy and the BTK inhibitors ibrutinib or acalabrutinib. The
objectives of the study are to evaluate the efficacy and safety
after a single infusion of KTE-X19 in this patient population. The
primary endpoint for the study is objective response rate and is
defined as the combined rate of complete responses and partial
responses as assessed by an Independent Radiology Review Committee.
Secondary endpoints include duration of response, best objective
response, progression-free survival, OS, incidence of AEs,
incidence of anti-CD19 CAR antibodies, levels of anti-CD19 CAR T
cells in blood, levels of cytokines in serum, and changes over time
in the EQ-5D scale score and visual analogue scale score. The study
is ongoing.
About ZUMA-18
The U.S. expanded-access ZUMA-18 trial consists of two cohorts
of 27 patients per total. The primary objectives were to provide
access to Tecartus for patients with R/R MCL until it was
commercially available (Cohort 1) and patients with R/R MCL whose
manufactured product did not meet commercial release specifications
(Cohort 2). In Cohort 1, adults (≥18 years) with R/R MCL with ≥1
prior regimen underwent leukapheresis and conditioning chemotherapy
followed by a single infusion of Tecartus at a target dose of 2×106
cells/kg (or fixed dose of 2x108 anti-CD19 CAR T cells for patients
who are ≥100 kg). In Cohort 2, patients received Cohort 1 treatment
without leukapheresis (initial leukapheresis product used). Key
endpoints were safety, ORR, and OS.
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. Approximately 33,000
people worldwide are diagnosed with MCL each year. MCL is highly
aggressive following relapse, with many patients’ disease
progressing following therapy.
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, and is very challenging to treat. In adults, B-ALL is
the most common form, accounting for 75% of cases. Survival rates
in adults with R/R B-ALL are poor, with a median OS of 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 CIBMTR
The Center for International Blood and Marrow Transplant
Research is a nonprofit research collaboration between the NMDP/Be
The Match, in Minneapolis, and the Medical College of Wisconsin, in
Milwaukee. CIBMTR collaborates with the global scientific community
to increase survival and enrich quality of life for patients.
CIBMTR facilitates critical observational and interventional
research through scientific and statistical expertise, a large
network of centers, and a unique database of long-term clinical
data for more than 635,000 people who have received hematopoietic
cell transplantation and other cellular therapies. Learn more at
cibmtr.org.
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 supply and commercial product
manufacturing.
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 ability of Gilead and Kite 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 studies, including those involving Tecartus;
the possibility that Gilead and Kite may make a strategic decision
to discontinue development of programs for indications currently
under evaluation and, as a result, such indications may never be
successfully commercialized; the risk that physicians may not see
the benefits of prescribing Tecartus; and any assumptions
underlying any of the foregoing. These and other risks,
uncertainties and factors are described in detail in Gilead’s
Quarterly Report on Form 10-Q for the quarter ended September 30,
2023, 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. The reader is cautioned that any such forward-looking
statements are not guarantees of future performance and is
cautioned not to place undue reliance on these forward-looking
statements. 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.
Kite, the Kite logo, Tecartus, XLP and GILEAD
are trademarks of Gilead Sciences, Inc., or its related
companies.
For more information about 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 X (@KitePharma) and LinkedIn.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231211109742/en/
Jacquie Ross, Investors investor_relations@gilead.com
Meaghan Smith, Gilead Media msmith@gilead.com
Anna Padula, Kite Media apadula@kitepharma.com
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