Updated Phase 1 Data of Investigational AMG
420 in Relapsed and/or Refractory Multiple Myeloma Highlighted in
Oral Presentation and Accepted for Best of ASCO®
Investigational AMG 212 (Pasotuxizumab) Phase
1 Study Explores Use of BiTE Platform in a Solid Tumour
MISSISSAUGA, ON, June 5, 2019 /CNW/ - Amgen (NASDAQ:AMGN) today
announced new data from Phase 1 studies evaluating investigational
bispecific T cell engager (BiTE®) molecules were
presented at the 55th Annual Meeting of the American
Society of Clinical Oncology (ASCO) in Chicago. Data presented included updated
investigational AMG 420 results in patients with relapsed and/or
refractory multiple myeloma (R/R MM), as well as initial results
from the investigational AMG 212 (pasotuxizumab) first-in-human
trial in patients with metastatic castration-resistant prostate
cancer (mCRPC). BiTE technology is a targeted immuno-oncology
platform that is designed to engage patients' own T cells to a
tumour-specific antigen, activating the cytotoxic potential of T
cells. Both products are investigational only and are not currently
approved in any country.
"Our BiTE immuno-oncology platform offers unique
versatility, with the potential to treat various tumours through
targeting tumour-associated antigens," said David M. Reese, M.D., executive vice president
of Research and Development at Amgen. "As a leader in the
development of targeted immuno-oncology therapies, we continue to
investigate and advance more than a dozen BiTE molecules across a
broad range of hematologic malignancies and solid tumours. These
data at the ASCO Annual Meeting reinforce the potential of BiTE
technology for difficult-to-treat cancers like multiple myeloma and
prostate cancer."
ASCO Annual Meeting Abstract #8007: Evaluation of AMG 420, An
Anti-BCMA Bispecific T Cell Engager (BiTE) Immunotherapy, In R/R
Multiple Myeloma (MM) Patients: Updated Results of a First-in-Human
(FIH) Phase 1 Dose-Escalation Study
Updated results from a Phase 1, first-in-human dose-escalation
trial of investigational AMG 420, a B-cell maturation antigen
(BCMA)-targeting BiTE molecule, in patients with R/R MM were shared
during an oral presentation at the ASCO Annual Meeting. This
abstract was also selected for inclusion in the Best
of ASCO® educational program. The objectives
of the study included assessment of the safety, tolerability and
anti-tumour activity of AMG 420 per International Myeloma Working
Group 2006 Uniform Response Criteria for Multiple Myeloma. In the
study, 42 patients with R/R MM who had progression after at least
two prior lines of treatment (including a proteasome inhibitor and
an immunomodulatory drug) received AMG 420 at varying doses [0.2 to
800 µg/day (d)]. Of the doses tested in this study, 400 µg/d was
the maximum tolerated dose (MTD).
As of the latest readout, AMG 420 induced clinical responses in
13 of 42 patients across the dosing cohorts. Of the six patients
that achieved a minimal residual disease (MRD)-negative complete
response (CR), five were treated at the 400 µg/d dose. In addition,
at the 400 µg/d dose, one patient achieved a very good partial
response, and one achieved a partial response. The overall response
rate at 400 µg/d was 70 per cent (7/10). The median duration of
response was nine months (range 5.8-13.6 months). Median time to
response was one month, with 11 of 13 patients responding in the
first cycle.
Serious adverse events (AEs) were reported in 19 patients (45
percent). Sixteen required hospitalization and four had prolonged
hospitalization. No grade 3 or 4 central nervous system toxicities
were observed. Serious AEs occurring in more than one patient
included infections (n=13) and peripheral polyneuropathy (n=2).
Treatment-related serious AEs included polyneuropathy (n=2, both
grade 3) and edema (n=1, grade 3). Grade 3 cytokine release
syndrome (CRS) was seen in one patient. Two patients died during
the study from AEs not considered treatment-related. One patient
died 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.
ASCO 2019 Abstract #5034: Phase 1 Study of Pasotuxizumab (BAY
2010112), a PSMA-targeting BiTE (Bispecific T Cell Engager)
Immunotherapy for Metastatic Castration-Resistant Prostate Cancer
(mCRPC)
Initial results from a Phase 1 dose-escalation study of
investigational AMG 212 (pasotuxizumab, formerly known as BAY
2010112), in patients with mCRPC who are refractory to standard
therapy were presented in a poster at the ASCO Annual Meeting. AMG
212 is an investigational BiTE molecule which is designed to target
prostate-specific membrane antigen (PSMA), a promising target in
mCRPC. In the trial, 16 patients with mCRPC were enrolled into five
dosing cohorts, with a target dose range of 5 to 80 µg/d delivered
by continuous intravenous infusion. The primary objective was to
determine safety and MTD and secondary objectives included
pharmacokinetics (PK), biomarkers and tumour response. Antitumour
activity as indicated by decline in serum level of
prostate-specific antigen (PSA) was dose dependent. PSA decreases
of ≥ 50 percent occurred in three patients (n=1 each in 20 µg/d, 40
µg/d and 80 µg/d cohorts). One long-term responder was treated for
14 months (40 µg/d) and one for 19.4 months (80 µg/d). The latter
patient showed a complete regression of soft-tissue metastases and
regression of bone metastases, as well as an improvement in
disease-related symptoms. Recruitment in the trial was stopped
before MTD was reached to facilitate initiation of a new study
sponsored by Amgen.
"Metastatic castrate-resistant prostate cancer is considered a
heterogenous disease and despite advances made over the last few
years, the majority of patients face a poor outlook1,"
said Horst-Dieter Hummel, M.D.,
University Hospital of Wuerzburg, Germany, and AMG 212 clinical study
investigator. "In the first clinical study investigating the
potential of a BiTE molecule in solid tumours, AMG 212 showed
clinical activity, including two long-term responders. We look
forward to studying AMG 212 further in this patient
population."
The most common drug-related AEs were fever (94 percent, n=15)
and chills (69 percent, n=11). A drug-related serious AE (fatigue)
was reported in one patient. CRS was reported for three patients
(19 percent); two were grade 2 and one was grade 3. No grade 5 AEs
occurred.
Additional Updates on Amgen's BiTE Immuno-Oncology Platform
at ASCO 2019
Amgen continues to investigate the BiTE immuno-oncology
platform across a broad range of solid and hematologic
malignancies. Amgen is investigating more than a dozen
BiTE molecules across a range of solid and hematologic
malignancies, with an additional two trials-in-progress being
presented at the ASCO Annual Meeting.
During poster sessions, researchers shared information on the
studies of AMG 596, an investigational BiTE molecule targeting
epidermal growth factor receptor variant III (EGFRvIII) in
glioblastoma (GBM), and AMG 757, an investigational BiTE molecule
targeting delta-like ligand 3 (DLL3) in small-cell lung cancer
(SCLC). GBM and SCLC are both aggressive and difficult-to-treat
forms of cancer where there is a significant unmet medical need for
patients.
Forty-three percent of GBM tumours test positive for
amplification or mutation of the EGFR, the most common of which is
the EGFRvIII gain-of-function mutation.2 A Phase 1,
first-in-human, open-label, sequential dose-escalation and
dose-expansion study is ongoing for investigational AMG 596,
evaluating its safety, tolerability, and PK and pharmacodynamics in
patients with EGFRvIII-postive glioblastoma. The study is expected
to enroll 82 patients in two groups: one with recurrent GBM and a
second in newly diagnosed patients in the maintenance treatment
phase following standard of care treatment.
DLL3 is an inhibitory ligand of notch receptors that is
expressed in most SCLC tumours but minimally expressed in normal
tissues.3 An ongoing open-label, ascending,
multiple-dose, Phase 1 study is evaluating investigational AMG 757
in adult patients with SCLC which has progressed or recurred after
at least one platinum-based chemotherapy regimen. Primary
objectives are to evaluate safety and tolerability and to determine
the MTD or recommended Phase 2 dose. Secondary objectives are to
characterize PK and evaluate preliminary anti-tumour activity.
For more information on these and other ongoing clincial trials,
visit www.AmgenTrials.com.
About BiTE® Technology
BiTE® (Bispecific T cell engager) technology is a
targeted immuno-oncology platform that is designed to engage
patients' own T cells to any tumour-specific antigen,
activating the cytotoxic potential of T cells with the goal of
eliminating detectable cancer. The BiTE immuno-oncology platform
has the potential to treat different tumour types through
tumour-specific antigens. The BiTE platform has the goal of
off-the-shelf solutions, which have the potential to make
innovative T cell treatment available to all providers when their
patients need it. Amgen is advancing more than a dozen BiTE
molecules across a broad range of solid and hematologic
malignancies, further investigating BiTE technology with the goal
of enhancing patient experience and therapeutic potential.
About Amgen Canada
As a leader in innovation, Amgen Canada understands the value of
science. With main operations located in Mississauga, Ont.'s vibrant biomedical
cluster, and its research facility in Burnaby, B.C., Amgen Canada has been an
important contributor to advancements in science and innovation in
Canada since 1991. The company
contributes to the development of new therapies and new ways of
using existing medicines in partnership with many of Canada's leading health-care, academic,
research, government and patient organizations. To learn more about
Amgen Canada, visit www.amgen.ca.
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SOURCE Amgen Canada