RARITAN, N.J., Dec. 5, 2020 /PRNewswire/ -- The Janssen
Pharmaceutical Companies of Johnson & Johnson announced today
initial data for the Phase 1 first-in-human dose escalation study
of talquetamab (JNJ-64407564) for the treatment of relapsed or
refractory multiple myeloma (NCT03399799). Talquetamab is a
first-in-class, and the only investigational bispecific antibody
that targets both GPRC5D, a novel multiple myeloma target, and CD3
on T-cells. Initial results for both the subcutaneous (SC) and
intravenous (IV) formulations show encouraging clinical
activity against the GPRC5D target, which is highly expressed on
multiple myeloma cells and associated with poor prognostic
factors.1,2,3 At the SC recommended Phase 2 dose (RP2D),
the overall response rate (ORR) was 69 percent (9/13) and 39
percent achieved a very good partial response (VGPR) or better. The
data will be featured during the American Society of Hematology
(ASH) 2020 Annual Meeting as an oral presentation on Saturday, December 5 at 5:00 p.m. ET (Abstract #290).
"There is a pressing need for continued innovation of multiple
myeloma treatments – particularly for patients who have relapsed on
other therapies – and the results presented today for talquetamab
are encouraging," said Ajai Chari,
M.D., Professor of Medicine, the Director of Clinical Research in
the Multiple Myeloma Program, and the Associate Director of
Clinical Research, Mount Sinai Cancer Clinical Trials Office. "The
Phase 1 overall response rate and safety profile support further
study of talquetamab in monotherapy and in combination approaches
for patients with few options for treatment."
Investigators identified the RP2D of 405 µg/kg SC and concluded
subcutaneous treatment may provide an opportunity for less frequent
dosing than the intravenous formulation. A response was observed in
6/9 triple-class refractory patients and 2/2 penta-drug refractory
patients. Pharmacokinetic results indicate target exposure levels
at the RP2D. At the RP2D of 405 µg/kg SC, pharmacodynamic data
demonstrate consistent T-cell activation, cytokine production and
redistribution.
Patients received talquetamab at doses of 1–180 µg/kg with IV
administration and 5–800 µg/kg for the SC formulation. Results from
the Phase 1 study showed responses in patients who were treated
with talquetamab across dose groups; median time to first
confirmed response across all doses was one month (range,
0.2–3).4
The Phase 1 study enrolled patients (n=157) with multiple
myeloma who had progressed on, or could not tolerate, any available
established therapies. Patients had received a median of six prior
lines of treatment (range, 2-20); 87 percent were refractory to the
last line of therapy, 82 percent were triple-class refractory, and
33 percent were penta-drug refractory to two or more
immunomodulatory agents, two or more PIs, and an anti-CD38 therapy.
The study is conducted in two parts: dose escalation (part 1) and
dose expansion (part 2).4
In the Phase 1 study, adverse events (AEs) at the
RP2D which occurred with a Grade 3 frequency of ≥25 percent
among the SC cohort were neutropenia (42 percent). With SC
dosing, cytokine release syndrome (CRS) was observed in 64 percent
of patients and was low-grade with no Grade 3 or greater CRS events
at the RP2D. CRS occurred at a median of two days after dosing, and
median duration of CRS was also two days. The incidence of
neurotoxicity was five percent at the RP2D, with no patients
experiencing Grade 3 or greater events with SC
dosing.4
"GPRC5D is a novel target in the treatment of multiple myeloma
and, as a bispecific antibody that engages T-cells by also
targeting CD3, talquetamab is emerging as a potential therapeutic
option for heavily pretreated patients," said Yusri Elsayed, M.D., MHSc., Ph.D., Vice
President, Global Head, Hematologic Malignancies, Janssen Research
& Development, LLC. "Based on the preliminary efficacy, safety,
pharmacokinetic and pharmacodynamic data presented today, we are
committed to fully exploring the promise of talquetamab in multiple
myeloma."
About Talquetamab
Talquetamab is a first-in-class
investigational bispecific antibody targeting both GPRC5D, a novel
multiple myeloma target, and CD3, the T-cell
receptor.4 CD3 is involved in activating T-cells
and GPRC5D is highly expressed on multiple myeloma
cells.4,5,6 Results from preclinical
studies in mouse models demonstrate that talquetamab induces
T-cell-mediated killing of GPRC5D-expressing multiple myeloma cells
through the recruitment and activation of CD3-positive T-cells and
inhibits tumor formation and growth.6
Talquetamab is currently being evaluated in a Phase 1/2 clinical
study for the treatment of relapsed or refractory multiple myeloma
and is also being explored in combination studies. The development
of the antibody followed Janssen Biotech, Inc.'s licensing
agreement with Genmab for use of its DuoBody® technology
platform.*
*DuoBody® is a registered trademark of Genmab
A/S.
About Multiple Myeloma
Multiple myeloma is an
incurable blood cancer that affects a type of white blood cell
called plasma cells, which are found in the bone
marrow.7,8 When damaged, these plasma cells rapidly
spread and replace normal cells with tumors in the bone marrow. In
2020, it is estimated that more than 32,000 people will be
diagnosed and close to 13,000 will die from the disease in the
U.S.9 While some patients with multiple myeloma
have no symptoms, most patients are diagnosed due to symptoms,
which can include bone fracture or pain, low red blood cell counts,
tiredness, high calcium levels, 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 and Janssen Biotech, Inc.
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 talquetamab. 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 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.
1 Smith Sci Transl Med
11(485):eaau7746.
2 Pillarisetti Blood 135(15):1232.
3 Atamaniuk Eur J Clin Invest 42(9):953.
CD3, cluster of differentiation 3; MGUS, monoclonal gammopathy of
undetermined significance; SMM, smoldering multiple myeloma.
4 Chari A et al. A Phase 1, First-in-Human Study of
Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D
(GPRC5D) x CD3 Bispecific Antibody, in Patients with Relapsed
and/or Refractory Multiple Myeloma
(RRMM).: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408718/.
Accessed November 2020
5 Labrijn AF et al. Proc Natl Acad Sci USA. 2013;110:5145.
6 Cohen, Y., et al. Hematology. 2013 Nov;
18(6):348-51.
7 Kumar SK, et al. Leukemia. 2012 Jan;
26(1):149-57.
8 American Cancer Society. "What Is Multiple
Myeloma?." Available at:
http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma.
Accessed November 2020.
9 American Cancer Society: Cancer Facts &
Statistics. American Cancer Society | Cancer Facts &
Statistics.
https://cancerstatisticscenter.cancer.org/#!/cancer-site/Myeloma.
Accessed November 2020.
10 American Cancer Society. "Key Statistics About
Multiple Myeloma." Available at:
https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html.
Accessed January 2020.
Media Contacts:
Brian Kenney
Phone: +1 215-620-0111
Satu Glawe
Phone: +49 172-294-6264
Investor Relations:
Jennifer
McIntyre
Office: +1 732-524-3922
U.S. Medical Inquiries:
+1 800-526-7736
View original content to download
multimedia:http://www.prnewswire.com/news-releases/janssen-presents-first-data-from-the-phase-1-study-of-the-gprc5dxcd3-bispecific-talquetamab-in-patients-with-relapsed-or-refractory-multiple-myeloma-301186851.html
SOURCE Janssen Pharmaceutical Companies of Johnson &
Johnson