THOUSAND OAKS, Calif.,
Dec. 3, 2018 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced the first clinical
results from studies evaluating investigational novel bispecific T
cell engager (BiTE®) immunotherapies AMG 420 and AMG
330. In two separate Phase 1 dose escalation studies, AMG 420,
which targets B-cell maturation antigen (BCMA), and AMG 330, which
targets CD33, provided early evidence of tolerability and
anti-tumor activity in patients with relapsed and/or refractory
multiple myeloma and relapsed or refractory acute myeloid leukemia
(AML), respectively. These data were highlighted during oral
presentations at the 60th American Society of Hematology
(ASH) Annual Meeting & Exposition in San Diego.
BiTE® antibody construct technology, pioneered by
Amgen, is an innovative treatment approach that helps the body's
immune system attack cancer cells without the removal of immune
cells from the patient. Amgen is studying a number of
"off-the-shelf" investigational BiTE® immunotherapies,
with distinct targets, across a range of hematologic and solid
tumors.
"Building on our success with the only approved BiTE®
immunotherapy available for patients, Amgen is emphasizing our
commitment to the potential of this platform by advancing the
development of approximately a dozen novel molecules across
hematologic and solid tumor targets in hopes of continuing to offer
meaningful advances to patients in need," said David M. Reese, M.D., executive vice president
of Research and Development at Amgen. "We're encouraged by the
early results of investigational BiTE® immunotherapies
AMG 420 and AMG 330, especially when considered in the context of
these heavily pre-treated patients, many of whom have run out of
available options. We look forward to sharing more results from our
BiTE® pipeline at future medical meetings."
ASH Abstract #1010: Treatment with AMG 420, an anti-B-Cell
Maturation Antigen (BCMA) Bispecific T-cell Engager
(BiTE®) Antibody Construct, Induces Minimal Residual
Disease (MRD) Negative Complete Responses in Relapsed and/or
Refractory (R/R) Multiple Myeloma (MM) Patients: Results of a
First-in-Human (FIH) Phase 1 Dose Escalation Study
The data shared at ASH were the first presentation of all
endpoints from this Phase 1 dose-escalation trial of AMG 420 in
patients with relapsed and/or refractory multiple myeloma. The
objectives of the study included assessment of safety, tolerability
and anti-tumor activity of AMG 420 per International Myeloma
Working Group 2006 Uniform Response Criteria for Multiple
Myeloma.
In the study, 42 patients with relapsed and/or refractory
multiple myeloma who had progression after at least two prior lines
of treatment (including a proteasome inhibitor and an
immunomodulatory imide drug) received AMG 420 at varying doses [0.2
to 800 µg/day (d)]. AMG 420 induced clinical responses in 13
patients, including complete responses (CR) in seven patients. Four
patients treated at the 400 µg/d dose achieved minimal residual
disease (MRD) negative complete responses, meaning that no cancer
cells were detectable in the bone marrow. The objective response
rate at 400 µg/d was 70 percent (seven of 10 patients), with six
patients still responding up to 7.5 months. One dose-limiting
toxicity was observed up to the 400 µg/d dose (peripheral
polyneuropathy, which improved to baseline after intravenous
immunoglobulin and corticosteroid treatment).
Of those patients with serious adverse events (AEs) (n=20, 48
percent), 17 required hospitalization and four had prolonged
hospitalization. Serious AEs included infections (n=12), peripheral
polyneuropathy (n=2), and one each of liver failure, cardiac
failure, edema, biliary obstruction, spinal cord compression, renal
failure and weight loss. Treatment-related serious AEs included
polyneuropathy (n=2, both grade 3) and edema (n=1, grade 3).
Cytokine release syndrome (CRS) was seen in 16 patients (grade 1,
n=13; grade 2, n=2; grade 3, n=1). In this study, 800 µg/d was
determined to not be tolerable, as two out of the three patients
treated at this dose experienced dose-limiting toxicities.
Two patients died during the course of the study from AEs not
considered treatment-related. One patient died after the first
cycle of treatment from acute respiratory distress due to
concurrent flu and aspergillosis. The second patient died from
liver failure secondary to a viral infection during the course of
treatment.
"These first-in-human data of a BCMA-targeting BiTE®
immunotherapy showed encouraging evidence of AMG 420 activity, with
no major toxicities up to the 400 µg/d dose in patients with
relapsed and/or refractory multiple myeloma who received a median
of four prior therapies," said Max S.
Topp, M.D., professor, Hospital of Wuerzburg, Germany and AMG 420 clinical study
investigator. "Despite recent treatment advances, multiple myeloma
continues to be a disease characterized by cycles of relapse and
recurrence requiring additional therapies to help control the
disease."
Additionally, AMG 420 was granted Fast Track Designation by the
U.S. Food and Drug Administration (FDA). Fast track is a process
designed to facilitate the development, and expedite the review of
drugs to treat serious conditions and fill an unmet medical need.
The purpose is to get important new drugs to the patient earlier.
Fast Track addresses a broad range of serious conditions.
ASH Abstract #25: A Phase 1 First-in-Human Study of AMG 330,
an Anti-CD33 Bispecific T-cell Engager (BiTE®) Antibody
Construct, in Relapsed/Refractory Acute Myeloid Leukemia (R/R
AML)
In a separate first-in-human Phase 1 dose escalation study, 40
patients with relapsed or refractory AML were enrolled to receive
AMG 330 in 12 dose cohorts with a target dose range of 0.5 to 480
µg/d. The study objectives were to evaluate the safety,
pharmacokinetics and pharmacodynamics of AMG 330 and to estimate
the maximum tolerated dose. Results showed that two patients in the
trial achieved a CR at the 240 µg/d dose and two patients achieved
a CR with incomplete blood count recovery, one at the 240 µg/d dose
and one at the 120 μg/d dose. The CRs were not sustained beyond one
cycle of treatment.
Patients in the trial received a median of one (range: 1-6)
cycle with AMG 330; the majority of patients discontinued treatment
for disease progression. Other reasons for study
discontinuation included AEs (n=6, 2 treatment-related) and patient
request (n=2).
Serious AEs were seen in 73 percent of patients
(treatment-related in 17 patients). The most common serious AEs
seen in more than one patient included CRS (n=11), febrile
neutropenia (n=7), pneumonia (n=4), leukopenia (n=4), pyrexia
(n=3), thrombocytopenia (n=3) and subdural hematoma (n=2). One
patient died on study due to AML progression and one due to
intracranial hemorrhage (neither treatment-related). There were
dose-limiting toxicities of grade 2 CRS and grade 4 ventricular
fibrillation with a target dose of 480 μg/d administered as a
single-step regimen.
"The majority of adult AML patients will not be cured with
standard chemotherapy, underscoring the need for innovative
treatment options for those who have relapsed or are refractory to
currently available treatments1," said Farhad Ravandi, M.D., Janiece and Stephen A. Lasher professor of
medicine and chief of section of Developmental Therapeutics in the
Department of Leukemia at the University of
Texas – MD Anderson Cancer Center and AMG 330 clinical study
investigator. "These early data are encouraging as they indicate
AMG 330 may have anti-leukemic activity in heavily pretreated
patients with relapsed or refractory AML, validating the need for
continued evaluation of the BiTE® platform in targeting
CD33."
About
BiTE® Technology
Bispecific T cell
engager (BiTE®) antibody construct is an innovative
technology that can be engineered to target any tumor antigen
expressed by any type of cancer. The protein molecules are designed
to kill malignant cells using the patient's own immune system by
bridging T cells to tumor cells. BiTE® antibody
construct helps connect the T cells to the targeted cell, with the
intent of causing T cells to inject toxins which trigger cancer
cell death (apoptosis). Amgen is developing
BiTE® antibody constructs to uniquely (or
specifically) target numerous hematologic malignancies and solid
tumors.
About Amgen's Commitment to Oncology
Amgen
is committed to helping patients take on some of the toughest
cancers, such as those that have been resistant to drugs, those
that progress rapidly through the body and those where limited
treatment options exist. Amgen's supportive care
treatments help patients combat certain side effects of strong
chemotherapy, and our targeted medicines and immunotherapies focus
on more than a dozen different malignancies, ranging from blood
cancers to solid tumors. With decades of experience providing
therapies for cancer patients, Amgen continues to grow
its portfolio of innovative and biosimilar oncology medicines.
For more information, follow us on
www.twitter.com/amgenoncology.
About Amgen
Amgen is committed to unlocking
the potential of biology for patients suffering from serious
illnesses by discovering, developing, manufacturing and delivering
innovative human therapeutics. This approach begins by using tools
like advanced human genetics to unravel the complexities of disease
and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and
leverages its expertise to strive for solutions that improve health
outcomes and dramatically improve people's lives. A biotechnology
pioneer since 1980, Amgen has grown to be one of the
world's leading independent biotechnology companies, has reached
millions of patients around the world and is developing a pipeline
of medicines with breakaway potential.
For more information, visit www.amgen.com and follow
us on www.twitter.com/amgen.
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CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(Media)
Andrea Fassaceisa, 805- 905-2575 (Media)
Arvind Sood, 805-447-1060
(Investors)
References
1. Bose P, Vachhani P,
Cortex E. Treatment of Relapsed/Refractory Acute Myeloid Leukemia.
Curr Treat Options Oncol. 2017;18(3):17.
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