Combined results from Phase 1b/2 CARTITUDE-1
study presented at ASH 2020 show 97 percent overall response rate
at median follow-up of 12.4 months1
The Janssen Pharmaceutical Companies of Johnson & Johnson
announced today longer-term results from the combined Phase 1b/2
CARTITUDE-1 study (NCT03548207) evaluating the efficacy and safety
of ciltacabtagene autoleucel (cilta-cel), an investigational B cell
maturation antigen (BCMA)-directed chimeric antigen receptor T cell
(CAR-T) therapy, for the treatment of patients with relapsed and/or
refractory multiple myeloma. These data, presented as an oral
presentation at the American Society of Hematology (ASH) 2020
Annual Meeting (Abstract #177), continued to demonstrate a very
high overall response rate of 97 percent, which deepened over time
with 67 percent of patients achieving a stringent complete
response.1 With a median follow-up of 12.4 months, median duration
of response and progression-free survival (PFS) were not
reached.1
“Unfortunately, for patients with multiple myeloma for whom at
least three established treatment regimens have stopped working,
the prognosis is often not good,” said Deepu Madduri,* M.D.,
Assistant Professor of Medicine, Hematology and Medical Oncology,
The Tisch Cancer Institute at Mount Sinai, New York, and principal
study investigator. “In the CARTITUDE-1 study, heavily pretreated
patients, including those who were triple-class refractory,
achieved an impressive response following a single infusion of
ciltacabtagene autoleucel.”
Median time to first response was one month (range, 0.9-8.5),
with responses observed at a low dose of CAR-T cells (median
administered dose 0.71x106 CAR+ viable T cells/kg) and were ongoing
in 72 percent (n=70) of patients. Additionally, 93 percent of
evaluable patients (n=53) achieved minimal residual disease (MRD)
negative disease status at 10-5.1 The trial included heavily
pretreated patients, with evaluated patients having received a
median of six prior treatment regimens (range, 3-18); 88 percent
(n=85) were triple-refractory, 42 percent (n=41) were
penta-refractory, and 99 percent (n=96) were refractory to the last
line of therapy.1 The 12-month PFS rate was 77 percent (95 percent
confidence interval [CI], 66-84).1 The 12-month overall survival
(OS) rate was 89 percent (95 percent CI, 80-94) and manufacturing
of cilta-cel was successful for all patients.1
“The combined Phase 1b/2 data from the CARTITUDE-1 study include
a larger patient population than previously reported in the initial
Phase 1b results, and we are encouraged that patients treated with
cilta-cel continued to achieve impressive, deep responses,” said
Sen Zhuang, M.D., Ph.D., Vice President, Clinical Research
Development, Janssen Research & Development, LLC. “The
responses also appeared to be durable as indicated by the estimate
that 89 percent of patients remained alive and 77 percent of
patients remained progression-free after one year of follow
up.”
“We are committed to applying the best science and disease
insights to bring transformational therapies for people living with
blood cancers,” adds Dr Catherine Taylor, Vice President, Medical
Affairs Therapeutic Area Strategy, Europe, Middle East and Africa
(EMEA), Janssen-Cilag Ltd., Middle East. “We are excited to see
these latest results reinforce the early promising data previously
presented and hope that one day cilta-cel can offer a viable
treatment option for multiple myeloma patients who have limited
therapeutic options.”
In these combined results, the most common haematologic adverse
events (AEs) observed in the CARTITUDE-1 study were neutropenia (96
percent); anemia (81 percent); thrombocytopenia (79 percent);
leukopenia (62 percent); and lymphopenia (53 percent).1 Cytokine
release syndrome (CRS) of any grade was observed in 95 percent of
patients, with a median duration of four days (range, 1-97), and 99
percent of which were resolved within 14 days of onset.1 Of the 92
patients with CRS, 95 percent (n=87) were Grade 1/2, three percent
(n=3) were Grade 3, one percent (n=1) was Grade 4 and one percent
(n=1) was Grade 5.1 The median onset of CRS was at seven days
(range, 1-12) post-infusion, with 89 percent (n=82) of patients
experiencing CRS onset at day four or later.1
Neurotoxicity of any grade was observed in 21 percent (n=20) of
patients, with Grade 3 or higher neurotoxicity observed in 10
percent (n=10) of patients.1 Of these, Immune effector
Cell-Associated Neurotoxicity Syndrome (ICANS) was observed in 16
patients; other neurotoxicities were observed in 12 patients and
generally occurred after resolution of CRS and/or ICANS.1 ICANS
events were resolved in all patients with a median time to recovery
of four days (range, 1-12).1 Other neurotoxicities were resolved in
six patients with a median time of 75 days (range, 2-160) and were
not resolved in six patients (one with ongoing toxicity, one died
from neurotoxicity and four died due to other causes).1 Fourteen
deaths were reported during the study: five due to disease
progression, three due to adverse events unrelated to treatment
(acute myelogenous leukemia (n=2), pneumonia (n=1)) and six due to
adverse events related to treatment (sepsis and/or septic shock
(n=2), CRS/ hemophagocytic lymphohistiocytosis (n=1), lung abscess
(n=1), respiratory failure (n=1) and neurotoxicity (n=1)).1
*Deepu Madduri is the lead investigator of the CARTITUDE-1
study. She was compensated for media work during the American
Society of Hematology (ASH) 2020 Annual Meeting
#ENDS#
About CARTITUDE-1
CARTITUDE-1 (NCT03548207) is an ongoing Phase 1b/2, open-label,
multicentre study evaluating the safety and efficacy of cilta-cel
in adults with relapsed and/or refractory multiple myeloma, 99
percent of whom were refractory to the last line of treatment; 88
percent of whom were triple-class refractory, meaning their cancer
did not, or no longer responds to an immunomodulatory agent (IMiD),
a proteasome inhibitor (PI) and an anti-CD38 antibody.1,2
The primary objective of the Phase 1b portion of the study,
involving 29 patients, was to characterise the safety and confirm
the dose of cilta-cel, informed by the first-in-human study with
LCAR-B38M CAR-T cells (LEGEND-2).2 Based on the safety profile
observed in this portion of the study.1 The Phase 2 portion of the
study, is evaluating the efficacy of cilta-cel with overall
response as the primary endpoint.1
About Ciltacabtagene Autoleucel
(cilta-cel) Cilta-cel is an investigational chimeric
antigen receptor T cell (CAR-T) therapy for the treatment of
patients with multiple myeloma. The design comprises a structurally
differentiated CAR-T with two BCMA-targeting single domain
antibodies.1 CAR-T cells are an innovative approach to eradicating
cancer cells by harnessing the power of a patient’s own immune
system.3 BCMA is a protein that is highly expressed on myeloma
cells.4
In December 2017, Janssen entered into an exclusive worldwide
license and collaboration agreement with Legend Biotech to develop
and commercialise cilta-cel.5 In May 2018, Janssen initiated a
Phase 1b/2 CARTITUDE-1 trial (NCT03548207) to evaluate the efficacy
and safety of cilta-cel in adults with relapsed and/or refractory
multiple myeloma, informed by the LEGEND-2 study results.2
In April 2019, cilta-cel was granted PRIME (PRIority MEdicines)
designation by the European Medicines Agency (EMA).6 PRIME offers
enhanced interaction and early dialogue to optimise drug
development plans and speed up evaluation of cutting-edge,
scientific advances that target a high unmet medical need.7 In
February 2020, the European Commission granted orphan designation
for cilta-cel.8
About Multiple Myeloma
Multiple myeloma (MM) is an incurable blood cancer that starts in
the bone marrow and is characterised by an excessive proliferation
of plasma cells.9 In Europe, more than 48,200 people were diagnosed
with MM in 2018, and more than 30,800 patients died.10 Around 50
percent of newly diagnosed patients do not reach five-year
survival,11,12 and almost 29 percent of patients with multiple
myeloma will die within one year of diagnosis.13
Although treatment may result in remission, unfortunately,
patients will most likely relapse as there is currently no cure.14
Refractory MM is when a patient’s disease progresses within 60 days
of their last therapy.15 Relapsed cancer is when the disease has
returned after a period of initial, partial or complete
remission.15 While some patients with MM have no symptoms at all,
others are diagnosed due to symptoms that can include bone
problems, low blood counts, calcium elevation, kidney problems or
infections.16 Patients who relapse after treatment with standard
therapies, including protease inhibitors and immunomodulatory
agents, have poor prognoses and require new therapies for continued
disease control.17
About the Janssen Pharmaceutical
Companies of Johnson & Johnson At Janssen, we’re
creating a future where disease is a thing of the past. We’re the
Pharmaceutical Companies of Johnson & Johnson, working
tirelessly to make that future a reality for patients everywhere by
fighting sickness with science, improving access with ingenuity,
and healing hopelessness with heart. We focus on areas of medicine
where we can make the biggest difference: Cardiovascular &
Metabolism, Immunology, Infectious Diseases & Vaccines,
Neuroscience, Oncology, and Pulmonary Hypertension. Learn more at
www.janssen.com/emea. Follow us at www.twitter.com/janssenEMEA for
our latest news. Janssen-Cilag Ltd., Middle East and Janssen
Research and Development, LLC are part of the Janssen
Pharmaceutical Companies of Johnson & Johnson.
# # #
Cautions Concerning Forward-Looking Statements This press
release contains "forward-looking statements" as defined in the
Private Securities Litigation Reform Act of 1995 regarding product
development and the potential benefits and treatment impact of
ciltacabtagene autoleucel. The reader is cautioned not to rely on
these forward-looking statements. These statements are based on
current expectations of future events. If underlying assumptions
prove inaccurate or known or unknown risks or uncertainties
materialize, actual results could vary materially from the
expectations and projections of Janssen Pharmaceutica NV and/or any
of the other Janssen Pharmaceutical Companies and/or Johnson &
Johnson. Risks and uncertainties include, but are not limited to:
challenges and uncertainties inherent in product research and
development, including the uncertainty of clinical success and of
obtaining regulatory approvals; uncertainty of commercial success;
manufacturing difficulties and delays; competition, including
technological advances, new products and patents attained by
competitors; challenges to patents; product efficacy or safety
concerns resulting in product recalls or regulatory action; changes
in behavior and spending patterns of purchasers of health care
products and services; changes to applicable laws and regulations,
including global health care reforms; and trends toward health care
cost containment. A further list and descriptions of these risks,
uncertainties and other factors can be found in Johnson &
Johnson's Annual Report on Form 10-K for the fiscal year ended
December 29, 2019, including in the sections captioned “Cautionary
Note Regarding Forward-Looking Statements” and “Item 1A. Risk
Factors,” and in the company’s most recently filed Quarterly Report
on Form 10-Q, and the company’s subsequent filings with the
Securities and Exchange Commission. Copies of these filings are
available online at www.sec.gov, www.jnj.com or on request from
Johnson & Johnson. Neither the Janssen Pharmaceutical Companies
nor Johnson & Johnson undertakes to update any forward-looking
statement as a result of new information or future events or
developments.
References
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Chimeric Antigen Receptor T Cell Therapy, in Relapsed/Refractory
Multiple Myeloma. Oral Presentation. To be presented at 2020
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Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation
Antigen (BCMA) in Participants With Relapsed or Refractory Multiple
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