- First analysis data from CARTITUDE-4 demonstrated a
statistically significant improvement in progression-free survival,
with a hazard ratio of 0.26
- CARTITUDE-4 is the first randomized study investigating the
efficacy of a cell therapy versus standard of care (DPd or PVd) as
early as after first relapse in lenalidomide-refractory multiple
myeloma
- Long-term results from CARTITUDE-1 and LEGEND-2 demonstrated
sustained deep and durable responses
Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a
global biotechnology company developing, manufacturing and
commercializing novel therapies to treat life-threatening diseases,
announced today that results from the Phase 3 CARTITUDE-4 study
showed that, at a median follow up of 16 months, cilta-cel reduced
the risk of disease progression or death by 74 percent compared to
standard of care regimens in adult patients with multiple myeloma
who have received one to three prior lines of therapy and are
refractory to lenalidomide (Hazard ratio [HR]=0.26 (95% CI,
0.18–0.38); P-value [P] <0.0001).1 The study data were featured
in a press briefing and presented in an oral session at the 2023
American Society of Clinical Oncology (ASCO) Annual Meeting
(Abstract #LBA106) and were presented in the New England Journal of
Medicine. On Saturday, June 10, 2023, results will also be
presented in a plenary session at the 2023 European Hematology
Association (EHA) Hybrid Congress (Abstract #S100).
Eligible patients in the CARTITUDE-4 study had one to three
prior lines of treatment, including proteasome inhibitors (PI) and
immunomodulatory drugs and were lenalidomide-refractory.1 Four
hundred and nineteen patients were randomized, with 208 patients in
the cilta-cel arm and 211 patients in the SOC arm. At the median
follow up of 16 months, the median PFS had not yet been reached in
the cilta-cel arm (95% CI, 22.8-NE), compared to a median PFS of
11.8 months in the SOC arm (95% CI: 9.7-13.8). In patients who had
one prior line of therapy, there was a 65 percent (HR=0.35; 95
percent CI, 0.19-0.66; P<0.0001) reduction in the risk of
disease progression or death. Among the secondary endpoints, the
overall response rate (ORR) was 85 percent, 73 percent achieved a
complete response (CR) or better, and the rate of overall minimal
residual disease (MRD) negativity reached 61 percent in the
cilta-cel arm.1 Among patients treated with SOC therapies, the ORR
was 67 percent, and 22 percent achieved a CR or better, while 33
percent of patients treated with SOC therapies were MRD
negative.1
“There continues to be a serious unmet need in multiple myeloma,
particularly in earlier lines of treatment,” said Binod Dhakal,
M.D., M.S., Associate Professor of Medicine at the Medical College
of Wisconsin, Division of Hematology, and study investigator. “The
CARTITUDE-4 results demonstrate the potential for cilta-cel to be
an additional treatment option for appropriate patients with
relapsed and refractory multiple myeloma who have had one to three
prior lines of therapy.”
In the study, 97 percent and 94 percent of patients treated in
the cilta-cel and SOC groups, respectively, had grade 3 or 4
adverse events, including infections (27 percent versus 25 percent)
and cytopenias (94 percent versus 86 percent).1 Overall, 39
patients in the cilta-cel arm and 46 patients in the SOC arms died,
of which 10 cilta-cel and 5 SOC patients passed due to
treatment-emergent adverse events (TEAEs).1 In patients who
received cilta-cel as study treatment (n=176), 76 percent had
cytokine release syndrome (1 percent grade 3; no grade 4 or 5) and
5 percent had immune effector cell associated neurotoxicity
syndrome (all grade 1 or 2).1 One grade 1 movement and
neurocognitive treatment-emergent adverse event was reported in the
cilta-cel group.1
“Data from CARTITUDE-4 demonstrated strong results for study
patients after first relapse,” said Mythili Koneru, M.D., Chief
Medical Officer at Legend Biotech. “We are inspired by the
potential of cilta-cel for patients with multiple myeloma who
continue to have a high need for another treatment option.”
Final Analysis of CARTITUDE-1 Study
Demonstrated Deep and Durable Responses
A final analysis of data from the Phase 1b/2 CARTITUDE-1
(NCT03548207) study showed sustained deep and durable responses in
heavily pretreated patients with relapsed or refractory multiple
myeloma treated with cilta-cel (Abstract #8009).2 At a median
follow-up of 33.4 months (range, 1.5-45.2), the median PFS was 34.9
months (95 percent CI, 25.2–not estimable [NE]), with an estimated
47.5 percent of patients progression-free and alive at 36
months.2
In the study, 97 patients received cilta-cel, with a median of
six prior lines of therapy.2 Forty-two percent of patients were
penta-drug refractory, 88 percent were triple-class refractory and
99 percent were refractory to the last line of treatment.2 At data
cut-off, the median duration of response was 33.9 months (95
percent CI, 25.5–NE).2 Median overall survival (OS) was not reached
in the study, with an estimated 62.9 percent OS rate at 36 months.2
Of 49 MRD-evaluable patients, 26 had MRD-negativity sustained for
12 months or longer, of which 20 had a sustained MRD-negative CR or
better.2 Eighteen patients were MRD-negative with a CR or better at
24-months post infusion.2 No new safety signals and no new
neurotoxicity events were reported since the 27.7-month median
follow-up.2 Six new cases of second primary malignancy were
reported, including two cases of basal cell carcinoma and one case
each of myelodysplastic syndrome, B-cell lymphoma, melanoma and
prostate cancer.2 Five additional deaths occurred in the study (PD,
n=3; pneumonia and sepsis, n=1 each, both determined by the
investigators to be unrelated to cilta-cel), for a total of 35
deaths in the study (PD, n=17; unrelated to cilta-cel, n=12;
related, n=6, as determined by investigators).2
Five-Year Follow-up Data from LEGEND-2
Highlights Sustained, Durable Responses
Five-year follow-up data from LEGEND-2, the longest follow-up
for any BCMA-targeted CAR-T cell therapy study investigating
LCAR-B38M, a similar CAR construct to cilta-cel, showed a median OS
of 55.8 months, with 18 percent of patients with heavily pretreated
multiple myeloma remaining disease-free.3
At the data cut-off, median follow-up in the LEGEND-2 study was
65.4 months (range, 0.4-78.8).3 Seventy-four patients received
LCAR-B38M, with a median of three prior lines of therapy (range,
1-9); 35.7 percent of patients had high risk cytogenic profiles.3
In the study, the ORR was 87.8 percent, and 73 percent of patients
achieved a CR.3 The median duration of response in the study was 23
months, and median PFS was 18 months at maturity, consistent with
previously reported data.3 The rate of MRD-negative CR was 67.6
percent.3 No new CAR-T cell-related toxicities were reported in the
analysis.3
Disclosure: Dr. Dhakal has provided consulting, advisory, and
speaking services to Legend Biotech and Janssen Biotech, Inc.
CARVYKTI® Important Safety Information
CARVYKTI® INDICATIONS AND USAGE
CARVYKTI® (ciltacabtagene autoleucel) is a B-cell maturation
antigen (BCMA)-directed genetically modified autologous T cell
immunotherapy indicated for the treatment of adult patients with
relapsed or refractory multiple myeloma, after four or more prior
lines of therapy, including a proteasome inhibitor, an
immunomodulatory agent, and an anti-CD38 monoclonal antibody.
CARVYKTI® IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME,
NEUROLOGIC TOXICITIES, HLH/MAS, and PROLONGED and RECURRENT
CYTOPENIA Cytokine Release Syndrome (CRS), including fatal
or life-threatening reactions, occurred in patients following
treatment with CARVYKTI®. Do not administer CARVYKTI® to patients
with active infection or inflammatory disorders. Treat severe or
life-threatening CRS with tocilizumab or tocilizumab and
corticosteroids. Immune Effector Cell-Associated
Neurotoxicity Syndrome (ICANS), which may be fatal or
life-threatening, occurred following treatment with CARVYKTI®,
including before CRS onset, concurrently with CRS, after CRS
resolution, or in the absence of CRS. Monitor for neurologic events
after treatment with CARVYKTI®. Provide supportive care and/or
corticosteroids as needed. Parkinsonism and Guillain-Barré
syndrome and their associated complications resulting in fatal or
life-threatening reactions have occurred following treatment with
CARVYKTI®. Hemophagocytic Lymphohistiocytosis/Macrophage
Activation Syndrome (HLH/MAS), including fatal and life-threatening
reactions, occurred in patients following treatment with CARVYKTI®.
HLH/MAS can occur with CRS or neurologic toxicities.
Prolonged and/or recurrent cytopenias with bleeding and
infection and requirement for stem cell transplantation for
hematopoietic recovery occurred following treatment with
CARVYKTI®. CARVYKTI® is available only through a restricted
program under a Risk Evaluation and Mitigation Strategy (REMS)
called the CARVYKTI® REMS Program.
WARNINGS AND PRECAUTIONS Cytokine Release Syndrome
(CRS) including fatal or life-threatening reactions, occurred
following treatment with CARVYKTI® in 95% (92/97) of patients
receiving ciltacabtagene autoleucel. Grade 3 or higher CRS (2019
ASTCT grade) occurred in 5% (5/97) of patients, with Grade 5 CRS
reported in 1 patient. The median time to onset of CRS was 7 days
(range: 112 days). The most common manifestations of CRS included
pyrexia (100%), hypotension (43%), increased aspartate
aminotransferase (AST) (22%), chills (15%), increased alanine
aminotransferase (ALT) (14%) and sinus tachycardia (11%). Grade 3
or higher events associated with CRS included increased AST and
ALT, hyperbilirubinemia, hypotension, pyrexia, hypoxia, respiratory
failure, acute kidney injury, disseminated intravascular
coagulation, HLH/MAS, angina pectoris, supraventricular and
ventricular tachycardia, malaise, myalgias, increased C-reactive
protein, ferritin, blood alkaline phosphatase and gamma-glutamyl
transferase.
Identify CRS based on clinical presentation. Evaluate for and
treat other causes of fever, hypoxia, and hypotension. CRS has been
reported to be associated with findings of HLH/MAS, and the
physiology of the syndromes may overlap. HLH/MAS is a potentially
life-threatening condition. In patients with progressive symptoms
of CRS or refractory CRS despite treatment, evaluate for evidence
of HLH/MAS.
Sixty-nine of 97 (71%) patients received tocilizumab and/or a
corticosteroid for CRS after infusion of ciltacabtagene autoleucel.
Forty-four (45%) patients received only tocilizumab, of whom 33
(34%) received a single dose and 11 (11%) received more than one
dose; 24 patients (25%) received tocilizumab and a corticosteroid,
and one patient (1%) received only corticosteroids. Ensure that a
minimum of two doses of tocilizumab are available prior to infusion
of CARVYKTI®.
Monitor patients at least daily for 10 days following CARVYKTI®
infusion at a REMS-certified healthcare facility for signs and
symptoms of CRS. Monitor patients for signs or symptoms of CRS for
at least 4 weeks after infusion. At the first sign of CRS,
immediately institute treatment with supportive care, tocilizumab,
or tocilizumab and corticosteroids.
Counsel patients to seek immediate medical attention should
signs or symptoms of CRS occur at any time.
Neurologic toxicities, which may be severe,
life-threatening or fatal, occurred following treatment with
CARVYKTI®. Neurologic toxicities included ICANS, neurologic
toxicity with signs and symptoms of parkinsonism, Guillain-Barré
Syndrome, peripheral neuropathies, and cranial nerve palsies.
Counsel patients on the signs and symptoms of these neurologic
toxicities, and on the delayed nature of onset of some of these
toxicities. Instruct patients to seek immediate medical attention
for further assessment and management if signs or symptoms of any
of these neurologic toxicities occur at any time.
Overall, one or more subtypes of neurologic toxicity described
below occurred following ciltacabtagene autoleucel in 26% (25/97)
of patients, of which 11% (11/97) of patients experienced Grade 3
or higher events. These subtypes of neurologic toxicities were also
observed in two ongoing studies.
Immune Effector Cell-Associated
Neurotoxicity Syndrome (ICANS): Patients may experience
fatal or life-threatening ICANS following treatment with CARVYKTI®,
including before CRS onset, concurrently with CRS, after CRS
resolution, or in the absence of CRS. ICANS occurred in 23% (22/97)
of patients receiving ciltacabtagene autoleucel including Grade 3
or 4 events in 3% (3/97) and Grade 5 (fatal) events in 2% (2/97).
The median time to onset of ICANS was 8 days (range 1-28 days). All
22 patients with ICANS had CRS. The most frequent (≥5%)
manifestation of ICANS included encephalopathy (23%), aphasia (8%)
and headache (6%).
Monitor patients at least daily for 10 days following CARVYKTI®
infusion at the REMS-certified healthcare facility for signs and
symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor
patients for signs or symptoms of ICANS for at least 4 weeks after
infusion and treat promptly. Neurologic toxicity should be managed
with supportive care and/or corticosteroids as needed.
Parkinsonism: Of the 25 patients in
the CARTITUDE-1 study experiencing any neurotoxicity, five male
patients had neurologic toxicity with several signs and symptoms of
parkinsonism, distinct from immune effector cell-associated
neurotoxicity syndrome (ICANS). Neurologic toxicity with
parkinsonism has been reported in other ongoing trials of
ciltacabtagene autoleucel. Patients had parkinsonian and
non-parkinsonian symptoms that included tremor, bradykinesia,
involuntary movements, stereotypy, loss of spontaneous movements,
masked facies, apathy, flat affect, fatigue, rigidity, psychomotor
retardation, micrographia, dysgraphia, apraxia, lethargy,
confusion, somnolence, loss of consciousness, delayed reflexes,
hyperreflexia, memory loss, difficulty swallowing, bowel
incontinence, falls, stooped posture, shuffling gait, muscle
weakness and wasting, motor dysfunction, motor and sensory loss,
akinetic mutism, and frontal lobe release signs. The median onset
of parkinsonism in the 5 patients in CARTITUDE-1 was 43 days (range
15-108) from infusion of ciltacabtagene autoleucel.
Monitor patients for signs and symptoms of parkinsonism that may
be delayed in onset and managed with supportive care measures.
There is limited efficacy information with medications used for the
treatment of Parkinson’s disease, for the improvement or resolution
of parkinsonism symptoms following CARVYKTI® treatment.
Guillain-Barré Syndrome: A fatal
outcome following Guillain-Barré Syndrome (GBS) has occurred in
another ongoing study of ciltacabtagene autoleucel despite
treatment with intravenous immunoglobulins. Symptoms reported
include those consistent with Miller-Fisher variant of GBS,
encephalopathy, motor weakness, speech disturbances and
polyradiculoneuritis.
Monitor for GBS. Evaluate patients presenting with peripheral
neuropathy for GBS. Consider treatment of GBS with supportive care
measures and in conjunction with immunoglobulins and plasma
exchange, depending on severity of GBS.
Peripheral Neuropathy: Six patients
in CARTITUDE-1 developed peripheral neuropathy. These neuropathies
presented as sensory, motor or sensorimotor neuropathies. Median
time of onset of symptoms was 62 days (range 4-136 days), median
duration of peripheral neuropathies was 256 days (range 2-465 days)
including those with ongoing neuropathy. Patients who experienced
peripheral neuropathy also experienced cranial nerve palsies or GBS
in other ongoing trials of ciltacabtagene autoleucel.
Cranial Nerve Palsies: Three
patients (3.1%) experienced cranial nerve palsies in CARTITUDE1.
All three patients had 7th cranial nerve palsy; one patient had 5th
cranial nerve palsy as well. Median time to onset was 26 days
(range 21-101 days) following infusion of ciltacabtagene
autoleucel. Occurrence of 3rd and 6th cranial nerve palsy,
bilateral 7th cranial nerve palsy, worsening of cranial nerve palsy
after improvement, and occurrence of peripheral neuropathy in
patients with cranial nerve palsy have also been reported in
ongoing trials of ciltacabtagene autoleucel. Monitor patients for
signs and symptoms of cranial nerve palsies. Consider management
with systemic corticosteroids, depending on the severity and
progression of signs and symptoms.
Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage
Activation Syndrome (MAS): Fatal HLH occurred in one patient
(1%), 99 days after ciltacabtagene autoleucel. The HLH event was
preceded by prolonged CRS lasting 97 days. The manifestations of
HLH/MAS include hypotension, hypoxia with diffuse alveolar damage,
coagulopathy, cytopenia, and multi-organ dysfunction, including
renal dysfunction. HLH is a life-threatening condition with a high
mortality rate if not recognized and treated early. Treatment of
HLH/MAS should be administered per institutional standards.
CARVYKTI® REMS: Because of the risk of CRS and
neurologic toxicities, CARVYKTI® is available only through a
restricted program under a Risk Evaluation and Mitigation Strategy
(REMS) called the CARVYKTI® REMS.
Further information is available at www.CARVYKTIrems.com or
1-844-672-0067.
Prolonged and Recurrent Cytopenias: Patients may exhibit
prolonged and recurrent cytopenias following lymphodepleting
chemotherapy and CARVYKTI® infusion. One patient underwent
autologous stem cell therapy for hematopoietic reconstitution due
to prolonged thrombocytopenia.
In CARTITUDE-1, 30% (29/97) of patients experienced prolonged
Grade 3 or 4 neutropenia and 41% (40/97) of patients experienced
prolonged Grade 3 or 4 thrombocytopenia that had not resolved by
Day 30 following ciltacabtagene autoleucel infusion.
Recurrent Grade 3 or 4 neutropenia, thrombocytopenia,
lymphopenia and anemia were seen in 63% (61/97), 18% (17/97), 60%
(58/97), and 37% (36/97) after recovery from initial Grade 3 or 4
cytopenia following infusion. After Day 60 following ciltacabtagene
autoleucel infusion, 31%, 12% and 6% of patients had a recurrence
of Grade 3 or higher lymphopenia, neutropenia and thrombocytopenia,
respectively, after initial recovery of their Grade 3 or 4
cytopenia. Eighty-seven percent (84/97) of patients had one, two,
or three or more recurrences of Grade 3 or 4 cytopenias after
initial recovery of Grade 3 or 4 cytopenia. Six and 11 patients had
Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the
time of death.
Monitor blood counts prior to and after CARVYKTI® infusion.
Manage cytopenias with growth factors and blood product transfusion
support according to local institutional guidelines.
Infections: CARVYKTI® should not be administered to
patients with active infection or inflammatory disorders. Severe,
life-threatening or fatal infections occurred in patients after
CARVYKTI® infusion.
Infections (all grades) occurred in 57 (59%) patients. Grade 3
or 4 infections occurred in 23% (22/97) of patients; Grade 3 or 4
infections with an unspecified pathogen occurred in 17%, viral
infections in 7%, bacterial infections in 1%, and fungal infections
in 1% of patients. Overall, four patients had Grade 5 infections:
lung abscess (n=1), sepsis (n=2) and pneumonia (n=1).
Monitor patients for signs and symptoms of infection before and
after CARVYKTI® infusion and treat patients appropriately.
Administer prophylactic, pre-emptive and/or therapeutic
antimicrobials according to the standard institutional guidelines.
Febrile neutropenia was observed in 10% of patients after
ciltacabtagene autoleucel 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 with
hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV),
HBV, hepatitis C virus (HCV), and human immunodeficiency virus
(HIV), or any other infectious agents if clinically indicated in
accordance with clinical guidelines before collection of cells for
manufacturing. Consider antiviral therapy to prevent viral
reactivation per local institutional guidelines/clinical
practice.
Hypogammaglobulinemia was reported as an adverse event in
12% (12/97) of patients; laboratory IgG levels fell below 500 mg/dL
after infusion in 92% (89/97) of patients. Monitor immunoglobulin
levels after treatment with CARVYKTI® and administer IVIG for IgG
<400 mg/dL. Manage per local institutional guidelines, including
infection precautions and antibiotic or antiviral prophylaxis.
Use of Live Vaccines: The safety of
immunization with live viral vaccines during or following CARVYKTI®
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 CARVYKTI® treatment, and
until immune recovery following treatment with CARVYKTI®.
Hypersensitivity Reactions have occurred in 5% (5/97) of
patients following ciltacabtagene autoleucel infusion. Serious
hypersensitivity reactions, including anaphylaxis, may be due to
the dimethyl sulfoxide (DMSO) in CARVYKTI®. Patients should be
carefully monitored for 2 hours after infusion for signs and
symptoms of severe reaction. Treat promptly and manage
appropriately according to the severity of the hypersensitivity
reaction.
Secondary Malignancies: Patients may develop secondary
malignancies. Monitor life-long for secondary malignancies. In the
event that a secondary malignancy occurs, contact Janssen Biotech,
Inc., at 1-800-526-7736 for reporting and to obtain instructions on
collection of patient samples for testing of secondary malignancy
of T cell origin.
Effects on Ability to Drive and Use Machines: Due to the
potential for neurologic events, including altered mental status,
seizures, neurocognitive decline, or neuropathy, patients are at
risk for altered or decreased consciousness or coordination in the
8 weeks following CARVYKTI® 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, and in the event of new onset of any
neurologic toxicities.
ADVERSE REACTIONS
The most common non-laboratory adverse reactions (incidence
greater than 20%) are pyrexia, cytokine release syndrome,
hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue,
infections of unspecified pathogen, cough, chills, diarrhea,
nausea, encephalopathy, decreased appetite, upper respiratory tract
infection, headache, tachycardia, dizziness, dyspnea, edema, viral
infections, coagulopathy, constipation, and vomiting. The most
common laboratory adverse reactions (incidence greater than or
equal to 50%) include thrombocytopenia, neutropenia, anemia,
aminotransferase elevation, and hypoalbuminemia.
Please read full Prescribing Information including Boxed Warning
for CARVYKTI®.
About CARVYKTI® (ciltacabtagene autoleucel;
cilta-cel)
Ciltacabtagene autoleucel is a BCMA-directed, genetically
modified autologous T-cell immunotherapy, which involves
reprogramming a patient’s own T-cells with a transgene encoding a
chimeric antigen receptor (CAR) that identifies and eliminates
cells that express BCMA. BCMA is primarily expressed on the surface
of malignant multiple myeloma B-lineage cells, as well as
late-stage B-cells and plasma cells. The cilta-cel CAR protein
features two BCMA-targeting single domain antibodies designed to
confer high avidity against human BCMA. Upon binding to
BCMA-expressing cells, the CAR promotes T-cell activation,
expansion, and elimination of target cells.4
In February 2022, cilta-cel was approved by the U.S. Food and
Drug Administration (FDA) under the brand name CARVYKTI® for the
treatment of adults with relapsed or refractory multiple myeloma.5
In May 2022, the European Commission (EC) granted conditional
marketing authorization of CARVYKTI® for the treatment of adults
with relapsed and refractory multiple myeloma.6 In September 2022,
Japan’s Ministry of Health, Labour and Welfare (MHLW) approved
CARVYKTI®.7 Cilta-cel was granted Breakthrough Therapy Designation
in the U.S. in December 2019 and in China in August 2020. In
addition, cilta-cel received a PRIority MEdicines (PRIME)
designation from the European Commission in April 2019. Cilta-cel
also received Orphan Drug Designation from the U.S. FDA in February
2019, from the European Commission in February 2020, and from the
Pharmaceuticals and Medicinal Devices Agency (PMDA) in Japan in
June 2020. In March 2022, the European Medicines Agency’s Committee
for Orphan Medicinal Products recommended by consensus that the
orphan designation for cilta-cel be maintained on the basis of
clinical data demonstrating improved and sustained complete
response rates following treatment.8
In December 2017, Legend Biotech entered into an exclusive
worldwide license and collaboration agreement with Janssen Biotech,
Inc. (Janssen) to develop and commercialize cilta-cel.
About CARTITUDE-4 CARTITUDE-4 (NCT04181827) is the first
international, randomized, open-label Phase 3 study evaluating the
efficacy and safety of a CAR-T therapy versus pomalidomide,
bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and
dexamethasone (DPd) in adult patients with relapsed and
lenalidomide-refractory multiple myeloma who received one to three
prior lines of therapy. After apheresis, patients randomized to the
cilta-cel arm of the study received either PVd or DPd as bridging
therapy, followed by an infusion of cilta-cel five to seven days
after lymphodepletion. In total, 176 patients received planned
cilta-cel treatment and 20 received cilta-cel after disease
progression during bridging therapy.1 In the SOC group, 28 patients
were treated with PVd and 183 patients were treated with DPd until
disease progression.1 The primary endpoint of the study is PFS.
Secondary endpoints include safety, overall survival (OS), minimal
residual disease (MRD) negative rate and overall response rate
(ORR). Patients will continue to be followed for primary and
secondary endpoints as part of the CARTITUDE-4 study.
About CARTITUDE-1 CARTITUDE-1 (NCT03548207) is a Phase
1b/2, open-label, single arm, multi-center trial evaluating
cilta-cel for the treatment of adult patients with relapsed or
refractory multiple myeloma, who previously received at least three
prior lines of therapy including a proteasome inhibitor (PI), an
immunomodulatory agent (IMiD) and an anti-CD38 monoclonal antibody.
Of the 97 patients enrolled in the trial, 99 percent were
refractory to the last line of treatment and 88 percent were
triple-class refractory, meaning their cancer did not respond, or
no longer responds, to an IMiD, a PI and an anti-CD38 monoclonal
antibody.
About LEGEND-2 LEGEND-2 (NCT03090659) is a Phase 1/2,
single-arm, open-label program in China comprised of four
independent institutional studies conducted at participating
hospitals evaluating the efficacy and safety of LCAR-B38M for the
treatment of patients with R/R multiple myeloma. LCAR-B38M
identifies the investigational product being studied in China and
Ciltacabtagene autoleucel (cilta-cel) identifies the
investigational product being studied in the U.S./EU, both of which
are representative of the same CAR-T therapy.
About Multiple Myeloma Multiple myeloma is an incurable
blood cancer that starts in the bone marrow and is characterized by
an excessive proliferation of plasma cells.9 In 2023, it is
estimated that more than 35,000 people will be diagnosed with
multiple myeloma, and more than 12,000 people will die from the
disease in the U.S.10 While some patients with multiple myeloma
have no symptoms at all, most patients are diagnosed due to
symptoms that can include bone problems, low blood counts, calcium
elevation, kidney problems or infections.11 Although treatment may
result in remission, unfortunately, patients will most likely
relapse.12 Patients who relapse after treatment with standard
therapies, including protease inhibitors, immunomodulatory agents,
and an anti-CD38 monoclonal antibody, have poor prognoses and few
treatment options available.13,14
About Legend Biotech Legend Biotech is a global
biotechnology company dedicated to treating, and one day curing,
life-threatening diseases. Headquartered in Somerset, New Jersey,
we are developing advanced cell therapies across a diverse array of
technology platforms, including autologous and allogeneic chimeric
antigen receptor T-cell, gamma-delta T cell (γδ T) and natural
killer (NK) cell-based immunotherapy. From our three R&D sites
around the world, we apply these innovative technologies to pursue
the discovery of safe, efficacious and cutting-edge therapeutics
for patients worldwide.
Learn more at www.legendbiotech.com and follow us on Twitter and
LinkedIn.
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
Statements in this press release about future expectations, plans
and prospects, as well as any other statements regarding matters
that are not historical facts, constitute “forward-looking
statements” within the meaning of The Private Securities Litigation
Reform Act of 1995. These statements include, but are not limited
to, statements relating to Legend Biotech’s strategies and
objectives; statements relating to CARVYKTI® and any other product
candidates, including Legend Biotech’s expectations for CARVYKTI®
and any other product candidates, such as the potential effect of
treatment with CARVYKTI® and any other product candidates; the
anticipated timing of, and ability to progress, clinical trials;
the ability to generate, analyze and present data from clinical
trials; expected results of clinical trials; and the potential
benefits of Legend Biotech’s product candidates. The words
“anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,”
“intend,” “may,” “plan,” “potential,” “predict,” “project,”
“should,” “target,” “will,” “would” and similar expressions are
intended to identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Actual
results may differ materially from those indicated by such
forward-looking statements as a result of various important
factors. Legend Biotech’s expectations could be affected by, among
other things, uncertainties involved in the development of new
pharmaceutical products; unexpected clinical trial results,
including as a result of additional analysis of existing clinical
data or unexpected new clinical data; unexpected regulatory actions
or delays, including requests for additional safety and/or efficacy
data or analysis of data, or government regulation generally;
unexpected delays as a result of actions undertaken, or failures to
act, by our third party partners; uncertainties arising from
challenges to Legend Biotech’s patent or other proprietary
intellectual property protection, including the uncertainties
involved in the U.S. litigation process; competition in general;
government, industry, and general product pricing and other
political pressures; the duration and severity of the COVID-19
pandemic and governmental and regulatory measures implemented in
response to the evolving situation; as well as the other factors
discussed in the “Risk Factors” section of Legend Biotech’s Annual
Report on Form 20-F filed with the Securities and Exchange
Commission on March 30, 2023. Should one or more of these risks or
uncertainties materialize, or should underlying assumptions prove
incorrect, actual results may vary materially from those described
in this press release as anticipated, believed, estimated or
expected. Any forward-looking statements contained in this press
release speak only as of the date of this press release. Legend
Biotech specifically disclaims any obligation to update any
forward-looking statement, whether as a result of new information,
future events or otherwise.
References
1 Dhakal, B. First phase 3 results from CARTITUDE-4: Cilta-cel
versus standard of care (PVd or DPd) in lenalidomide-refractory
multiple myeloma. To be presented at the 2023 American Society of
Oncology Annual Meeting and European Hematology Association 2023
Hybrid Congress. 2 Lin, Y. CARTITUDE-1 final results: Phase 1b/2
study of ciltacabtagene autoleucel in heavily pretreated patients
with relapsed/refractory multiple myeloma. To be presented at the
2023 American Society of Oncology Annual Meeting and European
Hematology Association 2023 Hybrid Congress. 3 Mi, J-Q. Long-Term
Remission and Survival in Patients with Relapsed or Refractory
Multiple Myeloma After Treatment of LCAR-B38M CAR-T – At Least
5-Year Follow-Up in LEGEND-2. To be presented at the 2023 American
Society of Oncology Annual Meeting and European Hematology
Association 2023 Hybrid Congress. 4 CARVYKTI™ Prescribing
Information. Horsham, PA: Janssen Biotech, Inc. 5 CARVYKTI™
(ciltacabtagene autoleucel), BCMA-Directed CAR-T Therapy, Receives
U.S. FDA Approval for the Treatment of Adult Patients with Relapsed
or Refractory Multiple Myeloma. Available at:
https://legendbiotech.com/legend-news/carvykti-ciltacabtagene-autoleucel-bcma-directed-car-t-therapy-receives-u-s-fda-approval-for-the-treatment-of-adult-patients-with-relapsed-or-refractory-multiple-myeloma/.
Accessed October 2022. 6 CARVYKTI (ciltacabtagene autoleucel)
Granted Conditional Approval by the European Commission for the
Treatment of Patients with Relapsed and Refractory Multiple
Myeloma. Available at:
https://legendbiotech.com/legend-news/carvykti-ciltacabtagene-autoleucel-granted-conditional-approval-by-the-european-commission-for-the-treatment-of-patients-with-relapsed-and-refractory-multiple-myeloma/.
Accessed October 2022. 7 CARVYKTI™ (ciltacabtagene autoleucel)
Receives Approval from Japan’s Ministry of Health, Labour and
Welfare (MHLW) for the Treatment of Patients with Relapsed or
Refractory Multiple Myeloma. Available at:
https://www.businesswire.com/news/home/20220926005847/en/CARVYKTI%E2%84%A2-ciltacabtagene-autoleucel-Receives-Approval-from-Japan%E2%80%99s-Ministry-of-Health-Labour-and-Welfare-MHLW-for-the-Treatment-of-Patients-with-Relapsed-or-Refractory-Multiple-Myeloma.
Accessed October 2022. 8 European Commission. Community Register of
Orphan Medicinal Products. Available at:
https://ec.europa.eu/health/documents/community-register/html/o2252.htm.
Accessed October 2022. 9 American Society of Clinical Oncology.
Multiple myeloma: introduction. https://www.cancer.net/cancer-
types/multiple-myeloma/introduction. Accessed October 2022. 10
American Cancer Society. "Key Statistics About Multiple Myeloma."
Available at:
https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html#:~:text=Multiple%20myeloma%20is%20a%20relatively,men%20and%2015%2C370%20in%20women).
Accessed January 2023. 11 American Cancer Society. Multiple
myeloma: early detection, diagnosis and staging.
https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf.
Accessed October 2022. 12 Rajkumar SV. Multiple myeloma: 2020
update on diagnosis, risk-stratification and management. Am J
Hematol. 2020;95(5),548-567. doi:10.1002/ajh.25791. 13 Kumar SK,
Dimopoulos MA, Kastritis E, et al. Natural history of relapsed
myeloma, refractory to immunomodulatory drugs and proteasome
inhibitors: a multicenter IMWG study. Leukemia. 2017;31(11):2443-
2448. 14 Gandhi UH, Cornell RF, Lakshman A, et al. Outcomes of
patients with multiple myeloma refractory to CD38- targeted
monoclonal antibody therapy. Leukemia. 2019;33(9):2266-2275.
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version on businesswire.com: https://www.businesswire.com/news/home/20230605005613/en/
Press Contact: Tina Carter, Corporate Communications
Lead, Legend Biotech tina.carter@legendbiotech.com (908) 331-5025
Investor Contacts: Joanne Choi, Senior Manager of Investor
Relations, Legend Biotech joanne.choi@legendbiotech.com Crystal
Chen, Manager of Investor Relations, Legend Biotech
crystal.chen@legendbiotech.cn
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