DUBLIN, Sept. 18, 2020 /PRNewswire/ -- Alkermes
plc (Nasdaq: ALKS) today presented new clinical data from
ARTISTRY-1, an ongoing phase 1/2 study evaluating Alkermes'
investigational engineered interleukin-2 (IL-2) variant
immunotherapy, ALKS 4230, administered intravenously as monotherapy
and in combination with the PD-1 inhibitor pembrolizumab
(KEYTRUDA®) in patients with refractory solid tumors.
Data from the ongoing ARTISTRY-1 study showed encouraging
single-agent activity of ALKS 4230 in melanoma and durable
responses in multiple tumor types in combination with
pembrolizumab. The most frequently observed treatment-emergent
adverse events (AEs) in both the monotherapy and combination
cohorts were transient fever and chills, consistent with
anticipated effects of immunotherapy. These data are being
presented in a mini oral presentation at the 2020 European Society
for Medical Oncology (ESMO) Virtual Congress, held Sept. 18-21. The company also announced today the
expansion of the ARTISTRY-1 monotherapy melanoma cohort based on
achievement of protocol-defined efficacy response criteria.
"New treatment options are needed to improve clinical outcomes
in many cancer types. Current immunotherapies are not an option for
all cancer types and only a portion of eligible patients respond to
them," said Ulka N. Vaishampayan,
M.D., Lead Investigator and Professor, Internal Medicine, Division
of Hematology/Oncology, University of
Michigan. "The monotherapy anti-tumor efficacy and the
durable responses in the combination cohorts in multiple tumor
types, including heavily pretreated platinum-resistant ovarian
cancer, triple-negative breast cancer and esophageal cancer,
provide additional insights into ALKS 4230's potential as a
treatment option for patients with advanced tumors that may not
respond to the current standard of care."
Data highlights include:
ALKS 4230 Monotherapy
The monotherapy expansion stage
of ARTISTRY-1 is evaluating the recommended phase 2 dose of ALKS
4230 (6 µg/kg/day) administered intravenously in patients with
refractory melanoma or refractory renal cell carcinoma (RCC). A
total of 15 patients across both monotherapy cohorts were treated,
with responses observed in melanoma. (Data as of July 24, 2020 unless otherwise noted.)
- Melanoma cohort
-
- Of the 5 evaluable melanoma patients (>1 scan), one had a
confirmed partial response (PR) and two had stable disease on at
least two consecutive scans.
- The PR was achieved in a patient with metastatic urethral
melanoma by week 20 of treatment, and a deepening of response was
observed through week 39 of treatment. This patient's serum lactate
dehydrogenase (LDH) levels, a known marker for treatment response
in melanoma, normalized at week 5 of treatment and remained within
the normal range throughout the treatment period. As of
July 27, 2020, the patient had
experienced a total tumor shrinkage of 39% and was continuing
monotherapy treatment.
- Since the July 24, 2020 data cut,
one additional melanoma patient achieved a PR, awaiting a
confirmatory scan. As of Sept. 1,
2020, this additional patient had experienced a total tumor
shrinkage of 39% and was continuing monotherapy treatment.
- With the observance of two PRs among the first 6 evaluable
patients in the monotherapy melanoma cohort, the protocol-defined
response criteria for expansion of this cohort was achieved, and
the cohort will now enroll up to 20 additional patients for a
total of up to 41 patients.
ALKS 4230 in Combination with Pembrolizumab
Data
presented at ESMO from the combination stage of ARTISTRY-1 included
data from patients in the PD-1/L1-approved, PD-1/L1-unapproved and
monotherapy rollover cohorts (n=67 total). Patients representing
more than 10 tumor types received ALKS 4230 3 µg/kg/day in
combination with pembrolizumab. Responses were observed across
multiple tumor types. (Data as of Aug. 7,
2020.)
- Refractory ovarian cancer
-
- Of the 13 evaluable patients (≥1 scan) with progressive,
refractory ovarian cancer, 9 demonstrated stable disease on their
first scan. Six of these 9 patients received a second scan by the
data cutoff date, and 5 had stable disease or better. All 5 of
these ovarian cancer patients were heavily pretreated and
platinum-resistant, and each experienced tumor burden reduction
with the combination of ALKS 4230 and pembrolizumab. Of these 5
patients:
-
- One patient with platinum-resistant ovarian cancer achieved a
complete response (CR) by week 45 of treatment, and a deepening of
response was observed through week 81 of treatment. As of the data
cut, this patient had a durable, confirmed CR and had remained on
treatment for more than 18 months.
- Two other patients with platinum-resistant ovarian cancer
achieved PRs, one confirmed and one unconfirmed. As of the data
cut, the patient with the confirmed PR demonstrated a deepening of
response and had remained on treatment for more than 5 months.
- Other tumor types
-
- Additional PRs were achieved in multiple other tumor types
across the PD-1/L1 approved and unapproved cohorts, including one
patient with triple-negative breast cancer and two patients with
esophageal cancer (one of which is awaiting confirmation). As of
the data cut, these three patients had sustained PRs and continued
on treatment.
Safety and Tolerability
(Data as of July 24, 2020 unless otherwise noted.)
- The safety profile of ALKS 4230 in combination with
pembrolizumab was generally consistent with the monotherapy
profile. Based on the data available, ALKS 4230 in combination with
pembrolizumab did not demonstrate any additive toxicity to that
already established with pembrolizumab alone.
- The most frequently observed treatment-emergent AEs in both the
monotherapy and combination groups were transient fever and chills,
all grade 1 or 2 in severity, which are consistent with anticipated
effects of cytokine therapy. One patient in the monotherapy cohort
had a grade 3 transient hypotension that was managed with fluids.
There were no reports of vascular leak syndrome, which is a known
AE associated with high-dose IL-2 treatment.
- There were no deaths due to treatment-related AEs in the
monotherapy cohorts. One death of a pancreatic cancer patient in
the combination cohort, which occurred after the data cutoff, was
due to inanition (starvation) and assessed as related to both study
drugs.
"The data presented at ESMO include early evidence of ALKS
4230's single-agent activity and its potential to deliver clinical
benefit in multiple tumor types as a combination therapy," said
Craig Hopkinson, M.D., Chief Medical
Officer and Executive Vice President of Research & Development
at Alkermes. "We're seeing increased momentum in enrollment trends
across the broader ARTISTRY clinical development program, and we
look forward to presenting our accumulating data for ALKS 4230 at
future medical meetings."
The mini oral presentation (#1027) titled, "ALKS 4230
Monotherapy and in Combination With Pembrolizumab in Patients With
Refractory Solid Tumors (ARTISTRY-1)," is available on the ESMO
website at www.esmo.org/meetings/esmo-virtual-congress-2020.
Conference Call and Webcast
Alkermes will host a
webcast presentation and conference call with accompanying slides
for analysts and investors on Friday, Sept.
18, 2020, at 8:30 a.m. ET
(1:30 p.m. BST) to discuss the latest
data from the ARTISTRY-1 clinical trial. The webcast will feature
the lead study investigator, Dr. Ulka N.
Vaishampayan, Professor of Internal Medicine, Division of
Hematology/Oncology, at the University of
Michigan, and members of Alkermes' management team. The
webcast player may be accessed on the Investors section of
Alkermes' website at www.alkermes.com. To participate in the
question and answer session, please also dial in to the conference
call, which may be accessed by dialing +1 877-407-2988 for U.S.
callers and +1 201-389-0923 for international callers. In addition,
a replay of the conference call may be accessed by visiting
Alkermes' website or by dialing +1 877-660-6853 for U.S. callers
and +1 201-612-7415 for international callers, using replay access
code 13708824. The conference call replay will be available from
11:30 a.m. ET (4:30 p.m. BST) on Friday,
Sept. 18, 2020 through Friday, Sept.
25, 2020.
About ALKS 4230
ALKS 4230 is an investigational,
novel, engineered fusion protein comprised of modified
interleukin-2 (IL-2) and the high affinity IL-2 alpha receptor
chain, designed to selectively expand tumor-killing immune cells
while avoiding the activation of immunosuppressive cells by
preferentially binding to the intermediate-affinity IL-2 receptor
complex. The selectivity of ALKS 4230 is designed to leverage the
proven anti-tumor effects of existing IL-2 therapy while mitigating
certain limitations.
About the ARTISTRY Clinical Development
Program
ARTISTRY is an Alkermes-sponsored clinical
development program evaluating ALKS 4230 in patients with advanced
solid tumors.
ARTISTRY-1 and ARTISTRY-2 are phase 1/2 studies
evaluating the safety, tolerability, efficacy and pharmacokinetic
and pharmacodynamic effects of ALKS 4230 in patients with
refractory advanced solid tumors, in both monotherapy and
combination settings with the PD-1 inhibitor pembrolizumab
(KEYTRUDA®). In ARTISTRY-1, ALKS 4230 is administered as
an intravenous infusion daily for five consecutive days. In
ARTISTRY-2, ALKS 4230 is administered subcutaneously and is being
evaluated with once-weekly and once-every-three-week dosing
schedules.
ARTISTRY-3 is a phase 2 study evaluating the clinical and
immunologic effects of ALKS 4230 monotherapy administered
intravenously on the tumor microenvironment of a variety of
advanced, malignant solid tumors.
About Alkermes
Alkermes plc is a fully integrated,
global biopharmaceutical company developing innovative medicines in
the fields of neuroscience and oncology. The company has a
portfolio of proprietary commercial products focused on addiction
and schizophrenia, and a pipeline of product candidates in
development for schizophrenia, bipolar I disorder,
neurodegenerative disorders, and cancer. Headquartered in
Dublin, Ireland, Alkermes plc has
an R&D center in Waltham,
Massachusetts; a research and manufacturing facility in
Athlone, Ireland; and a
manufacturing facility in Wilmington,
Ohio. For more information, please visit Alkermes' website
at www.alkermes.com.
Alkermes Note Regarding Forward-Looking
Statements
Certain statements set forth in this press
release constitute "forward-looking statements" within the meaning
of the Private Securities Litigation Reform Act of 1995, as
amended, including, but not limited to, statements concerning: the
potential therapeutic value of ALKS 4230 as a cancer immunotherapy
when used as monotherapy or in combination across multiple tumor
types; and the status of and plans for the clinical development of
ALKS 4230, including enrollment trends across the ARTISTRY clinical
development program, details of the ongoing ARTISTRY studies and
the company's plans for presentation of data relating to the
ARTISTRY development program. You are cautioned that
forward-looking statements are inherently uncertain. Although the
company believes that such statements are based on reasonable
assumptions within the bounds of its knowledge of its business and
operations, the forward-looking statements are neither promises nor
guarantees and they are necessarily subject to a high degree of
uncertainty and risk. Actual results may differ materially from
those expressed or implied in the forward-looking statements due to
various risks and uncertainties. These risks and uncertainties
include, among others, whether ALKS 4230, as a monotherapy or in
combination, could be shown to be unsafe or ineffective; whether
preclinical results and data from ongoing clinical studies for ALKS
4230—whether as a monotherapy or in combination—will be predictive
of future or final results from such studies, results of future
clinical studies or real-world results; whether future clinical
trials or future stages of ongoing clinical trials for ALKS 4230,
as a monotherapy or in combination, will be initiated or completed
on time or at all; changes in the cost, scope and duration of, and
clinical trial operations for, development activities for ALKS
4230, including changes relating to the impact of the novel
coronavirus (COVID-19) pandemic; and those risks and uncertainties
described under the heading "Risk Factors" in the company's Annual
Report on Form 10-K for the year ended Dec.
31, 2019, the company's Quarterly Report on Form 10-Q for
the quarter ended June 30, 2020 and
in subsequent filings made by the company with the U.S. Securities
and Exchange Commission (SEC), which are available on the SEC's
website at www.sec.gov. Existing and prospective investors are
cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date hereof. Except as
required by law, the company disclaims any intention or
responsibility for updating or revising any forward-looking
statements contained in this press release.
KEYTRUDA® is a registered trademark
of Merck Sharp & Dohme Corp.
Alkermes Contacts:
For Investors: Sandy Coombs, +1 781 609 6377
For Media: Sourojit Bhowmick, Ph.D.+1 781 609 6397
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SOURCE Alkermes plc