ORLANDO, Fla., Dec. 7, 2019 /PRNewswire/ -- The Janssen
Pharmaceutical Companies of Johnson & Johnson announced today
initial results from the Phase 1b/2
CARTITUDE-1 study (NCT03548207) evaluating the efficacy and safety
of JNJ-68284528 (JNJ-4528), an investigational B cell maturation
antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T)
therapy being evaluated in the treatment of patients with relapsed
or refractory multiple myeloma. The study enrolled patients who
have received at least three prior lines of therapy or are double
refractory to a proteasome inhibitor (PI) and an immunomodulatory
drug (IMiD); have received a PI, IMiD and an anti-CD38 antibody;
and who progressed on or within 12 months of their last line of
therapy. The CARTITUDE-1 study results, premiering at the 2019
American Society of Hematology (ASH) Annual Meeting, are featured
as an oral presentation and highlighted in the official ASH press
program (Abstract #577). These data also supported the recently
announced U.S. Food and Drug Administration Breakthrough Therapy
Designation for JNJ-4528.
Results from the Phase 1b portion
of the CARTITUDE-1 study showed early and deep responses among
patients (n=29) with a median of five prior multiple myeloma
treatment regimens (range, 3-18) treated with JNJ-4528 (median
administered dose 0.73x106 CAR+ viable T cells/kg), with
100 percent of patients achieving a response (95 percent confidence
interval [CI], 76-95) at a median six-month follow-up. The overall
response rate (ORR) included 69 percent of patients achieving a
complete response (CR) or better (66 percent achieving a stringent
CR); 86 percent of patients achieving a very good partial response
(VGPR) or better; and 14 percent of patients achieving a partial
response (PR). In addition, 100 percent of evaluable patients
achieved early minimal residual disease (MRD)-negative disease
status at day 28 post-infusion. At the six-month follow-up, 27 of
29 patients were progression-free. Based on the Phase 1b results, a recommended Phase 2 dose of
0.75x106 CAR+ viable T cells/kg was confirmed.
"These initial results from the Phase 1b portion of the CARTITUDE-1 study highlight a
compelling clinical profile for JNJ-4528 in heavily pre-treated
patients with relapsed or refractory multiple myeloma," said
Deepu Madduri, M.D., Assistant
Professor of Medicine, Hematology and Medical Oncology, Tisch
Cancer Institute at Mount Sinai, New
York, and principal study investigator. "With the
CARTITUDE-1 expansion cohort fully enrolled and all patients dosed,
we look forward to collecting additional efficacy and safety data
to further define the profile of this BCMA-targeted CAR-T
therapy."
The most common adverse events (AEs) observed in the CARTITUDE-1
study were cytokine release syndrome (CRS) (93 percent);
neutropenia (93 percent); anemia (86 percent); and thrombocytopenia
(86 percent). In patients who experienced grade 3 and above AEs (25
percent), the most common were neutropenia (93 percent);
thrombocytopenia (69 percent); and anemia (55 percent). A majority
of patients (86 percent) experienced grade 1-2 CRS. One patient
experienced grade 3 CRS and one patient died of complications from
grade 5 CRS at day 99. The median onset of CRS was generally
predictable at seven days (range, 2-12) post-infusion, with a
median duration of four days (range, 1-60).
"We are encouraged by the overall response reported in patients
receiving JNJ-4528, results that build upon the LEGEND-2 study data
as reported in Chinese patients and now show promise in U.S.
patients," said Sen Zhuang, M.D., Ph.D., Vice President,
Oncology Clinical Development, Janssen Research & Development,
LLC. "We are committed to advancing this novel BCMA-targeted
CAR-T therapy through clinical development and bringing this
immunotherapy to patients who are still in need of effective
therapies to rapidly control their disease."
JNJ-4528 is a structurally differentiated CAR-T with two
BCMA-targeting single domain antibodies.1 LCAR-B38M
identifies the investigational product in China, sponsored by Janssen development
partner, Legend Biotech. JNJ-4528 identifies the investigational
product with the same CAR construct being studied in the U.S. and
Europe.
Safety and efficacy results observed in the CARTITUDE-1 study
were consistent with the LEGEND-2 study of LCAR-B38M, sponsored by
Legend Biotech. In follow-up data from the LEGEND-2 study presented
at ASH (Abstract #579), investigators reported the long-term
response and safety profile for LCAR-B38M. Overall response rates
of 88 percent were observed, with 46 percent of all-treated
patients and 64 percent of the MRD-negative patients with CR
remaining progression-free. The median progression-free survival
(PFS) for all-treated patients was 20 months (range, 10–28); median
PFS for MRD-negative patients with CR was 28 months (range,
20–31).2
In a separate oral presentation (Abstract #928), data
highlighting post-infusion CAR+ T cell expansion in the bone marrow
and blood of patients enrolled in the CARTITUDE-1 study will be
reported. While both CD4+ and CD8+ CAR+ T cells expanded in
vivo, a preferential expansion of memory CD8+ CAR+ T cells was
observed at peak expansion. These and other correlative studies are
being conducted to better understand the immune mechanisms
associated with response to JNJ-4528, and suggest that the high
anti-myeloma activity of JNJ-4528 seen at a relatively low T cell
dose is potentially related to its preferential and consistent
in vivo expansion of CD8+ CAR+ T cells.
About CARTITUDE-1
CARTITUDE-1 (NCT03548207) is an
ongoing Phase 1b/2, open-label,
multicenter study evaluating the safety and efficacy of
JNJ-68284528 in adults with relapsed or refractory multiple myeloma
who have received at least three prior lines of therapy or are
double refractory to a PI and an IMiD; have received a PI, IMiD and
an anti-CD38 antibody; and who progressed on or within 12 months of
their last line of therapy. The primary objective of the Phase
1b portion of the study is to
characterize the safety and confirm the dose of JNJ-68284528, which
was informed by the first-in-human study with LCAR-B38M CAR-T cells
(LEGEND-2). The primary objective for the Phase 2 portion of the
study is to evaluate the efficacy of JNJ-68284528 (primary
endpoint: overall response rate as defined by the International
Myeloma Working Group response criteria).
About LEGEND-2
LEGEND-2 (NCT03090659) is an ongoing
Phase 1/2, single-arm, open-label study being conducted at four
participating hospitals in China
evaluating the efficacy and safety of LCAR-B38M for the treatment
of patients with relapsed or refractory multiple myeloma.
About JNJ-68284528 (LCAR-B38M)
JNJ-68284528
(LCAR-B38M) is an investigational chimeric antigen receptor T cell
(CAR-T) therapy for the treatment of patients with relapsed or
refractory multiple myeloma. The design comprises a structurally
differentiated CAR-T with two BCMA-targeting single domain
antibodies. In December 2017, Janssen
entered into an exclusive worldwide license and collaboration
agreement with Legend Biotech to develop and commercialize
JNJ-68284528 (LCAR-B38M). In May
2018, Janssen initiated a Phase 1b/2 trial (NCT03548207) to evaluate the efficacy
and safety of JNJ-68284528 in adults with relapsed or refractory
multiple myeloma, informed by the LEGEND-2 study results.
On December 6, Janssen announced
receipt of a Breakthrough Therapy Designation from the FDA, which
is granted to expedite the development and regulatory review of an
investigational medicine that is intended to treat a serious or
life-threatening condition. In February
2019, the FDA granted Janssen an Orphan Drug Designation for
JNJ-4528. In April
2019, JNJ-68284528 was granted PRIME (PRIority
MEdicines) designation by the European Medicines Agency (EMA).
PRIME offers enhanced interaction and early dialogue to optimize
development plans and speed up evaluation of cutting-edge,
scientific advances that target a high unmet medical
need.3
About CAR-T and BCMA
CAR-T cells are an innovative
approach to eradicating cancer cells by harnessing the power of a
patient's own immune system. BCMA is a protein that is highly
expressed on myeloma cells.
About Multiple Myeloma
Multiple myeloma is an
incurable blood cancer that occurs when malignant plasma cells grow
uncontrollably in the bone
marrow.4,5 Refractory cancer occurs when
a patient's disease is resistant to treatment or in the case of
multiple myeloma, when patients progress within 60 days of their
last therapy.6,7 Relapsed cancer means the disease
has returned after a period of initial, partial or complete
remission.8 In 2018, it is estimated
that 30,700 people will be diagnosed and 12,770 will die from the
disease in the U.S.9 Most patients are diagnosed
due to symptoms, which can include bone fracture or pain, low red
blood cell counts, fatigue, calcium elevation, kidney problems or
infections.10
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. Follow us at
www.twitter.com/JanssenGlobal and www.twitter.com/JanssenUS.
Janssen Research & Development, LLC is a member 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 JNJ-4528. 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 Research & Development, LLC 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 30, 2018, 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.
1 Fan F. Poster presented at the 17th
International Myeloma Workshop, September
12-15, 2019; Boston, MA.
Abstract number FP-181, #413.
2 Long-term follow-up of a Phase 1, first-in-human
open-label study of LCAR-B38M, a structurally differentiated CAR-T
cell therapy targeting BCMA, in patients with RRMM. 2019 ASH Annual
Meeting. December 2019.
3 European Medicines Agency. PRIME Factsheet. Available
at:
https://www.ema.europa.eu/en/human-regulatory/research-development/prime-priority-medicines.
Accessed December 2019.
4 Kumar SK, et al. Leukemia. 2012 Jan;
26(1):149-57.
5 American Cancer Society. "What Is Multiple
Myeloma?." Available at:
http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma.
Accessed December 2019.
6 National Cancer Institute. "NCI Dictionary of
Cancer Terms: Refractory." Available at:
https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=350245.
Accessed December 2019.
7 Richardson, et al. "The Treatment of Relapsed and
Refractory Multiple Myeloma." ASH Education Book. January 1, 2007 vol. 2007 no. 1. 317-323.
8 National Cancer Institute. "NCI Dictionary of
Cancer Terms: Relapsed." Available at:
https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45866.
Accessed December 2019.
9 American Cancer Society. "Key Statistics for
Multiple Myeloma." Available at:
https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html.
Accessed December 2019.
10 American Cancer Society. "Diagnosing Multiple
Myeloma From Test Results." Available at:
http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis.
Accessed December 2019.
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