Argos Therapeutics Inc. (Nasdaq:ARGS), an immuno-oncology company
focused on the development and commercialization of individualized
immunotherapies based on the Arcelis® precision immunotherapy
technology platform, today reported interim results from its
randomized, active controlled, open-label, multi-center Phase 3
ADAPT trial of Rocapuldencel-T in combination with
sunitinib/standard-of-care for the treatment of newly diagnosed
metastatic renal cell carcinoma (mRCC). The Company also provided
perspective on its decision to continue the trial.
A total of 462 patients were enrolled in the
ADAPT study and randomized 2:1 between combination treatment with
Rocapuldencel-T and sunitinib (combination arm) vs. sunitinib
monotherapy (control arm). For both arms, the protocol permits
switching to other standard-of-care treatments for mRCC for reasons
such as intolerance to therapy or disease progression. The primary
efficacy endpoint for the study is a statistically significant
improvement in overall survival, with secondary efficacy endpoints
evaluated to date of progression-free survival, objective response
rate and disease control rate, and an exploratory efficacy endpoint
of immune response. The trial was opened in January 2013 and
completed enrollment in July 2015 at 107 sites across North
America, Europe and Israel.
The most recent interim analysis was conducted
by the Independent Data Monitoring Committee (IDMC) in February
2017 (data cut-off as of February 3, 2017) after 75% of the
targeted number of 290 events (deaths) for the analysis of the
primary endpoint of overall survival had occurred. In accordance
with the statistical analysis plan, median overall survival was
estimated using the Kaplan-Meier method. At the time of the interim
analysis, the estimated median overall survival for the combination
arm was 27.7 months (95% Confidence Interval (CI): 23.0, 35.9)
compared to 32.4 months (95% CI: 22.5, -) for the control arm. The
hazard ratio was 1.10 (95% CI: 0.83, 1.46), which was greater than
the pre-defined futility boundary for the final interim analysis of
0.98. As a result, the IDMC recommended that the study be
discontinued for futility. The IDMC concluded that the study was
unlikely to demonstrate a statistically significant improvement in
overall survival in the combination arm, utilizing the
intent-to-treat population, the primary endpoint of the study. The
IDMC also noted that Rocapuldencel-T was generally well-tolerated
in the trial.
As previously reported, notwithstanding the IDMC
recommendation, the Company determined to continue to conduct the
trial pending further review and analysis of the data and
discussions with the FDA. This determination was made after
discussion of the results of the interim analysis with the ADAPT
trial principal investigators, Robert Figlin, MD (Cedars Sinai) and
Christopher Wood, MD (MD Anderson Cancer Center). In making this
determination, Argos considered, among other factors, the degree of
maturity of the data set, the mechanism of action of
Rocapuldencel-T, which involves the induction of long-term memory
immune responses, and the IDMC’s assessment of the safety profile
of Rocapuldencel-T. Of note, at the time of the IDMC’s February
interim analysis, the median duration of follow-up was 20.0 months
and more than half the patients in both treatment groups were still
alive.
Subsequent to the IDMC meeting, to explore the
hypothesis that longer follow-up time may provide useful
information to identify a potential beneficial effect of
Rocapuldencel-T, the Company conducted a post-hoc subgroup analysis
of overall survival in the first third of patients enrolled in the
study (n=154). In these patients, for whom generally the longest
follow-up data was available, the estimated median overall survival
for the combination arm was 30.1 months (95% CI: 23.3, -) compared
to 22.2 months (95% CI: 17.2, -) for the control arm. The hazard
ratio in this post-hoc subgroup analysis was 0.88 (95% CI: 0.56,
1.36).
In addition, also subsequent to the IDMC
meeting, the Company began conducting a pre-defined analysis of
immune responses, an exploratory efficacy endpoint, using
multi-parametric flow cytometry. Data available as of March 31,
2017 included 109 of the 190 samples from patients in the
combination arm, with analysis of the remaining samples ongoing.
Samples were collected from patients in the combination arm
enrolled at US sites who provided consent for immune monitoring. Of
the 109 subjects for whom this analysis was completed, 96 (88%) met
the criterion for inclusion in the pre-defined subgroup of immune
responders, suggesting that Rocapuldencel-T is having its intended
effect of stimulating an immune response in the majority of
patients. Immune responders are defined as patients who have an
increase of more than two standard deviations from the
patient-specific baseline in the number of memory T cells
(CD8+/CD28+/CD45RA-) at one or more time points. Of note, median
overall survival at the time of the February interim analysis had
not yet been reached in the subgroup of immune responders (95% CI:
30.1, -). Additionally, consistent with the mechanism of action of
Rocapuldencel-T, a statistically significant correlation was
observed between the increase from baseline in the number of
Rocapuldencel-T-induced memory T cells (CD8+/CD28+/CD45RA-) and
overall survival in patients for whom immune response data has been
analyzed and who received at least seven doses of Rocapuldencel-T
(including both immune responders and non-responders, n=72).
The Company continues to analyze the data from
the trial and plans to meet with the FDA in May 2017, but currently
believes based on the data it has reviewed that the trial should be
continued until completion. Based on these analyses and
discussions, the Company will make a determination as to the next
steps for the Rocapuldencel-T clinical program.
Conference Call and Webcast Details
Argos executive management will host a
conference call beginning at 4:30 p.m. Eastern Time today to
discuss these results and to answer questions. Argos management
will be presenting slides during the conference call and the slides
will be viewable under the Investors section of the Company’s
website at www.argostherapeutics.com. To participate by telephone,
please dial (855) 433-0930 (Domestic) or (484) 756-4271
(International). The conference ID number is 8568073. A live and
archived audio webcast with the accompanying slide presentation can
be accessed through the Investors section of the Company's website
at www.argostherapeutics.com. The archived webcast and accompanying
slide presentation will remain available on the Company's website
for twelve (12) months following the call.
About the Arcelis® Technology Platform
Arcelis® is a precision immunotherapy technology
that captures both mutated and variant antigens that are specific
to each patient's individual disease. It is designed to overcome
immunosuppression by producing a specifically targeted, durable
memory T cell response without adjuvants that may be associated
with toxicity. The technology is potentially applicable to the
treatment of a wide range of different cancers and infectious
diseases, and is designed to overcome many of the manufacturing and
commercialization challenges that have impeded other personalized
immunotherapies. The Arcelis® process uses only a small disease
sample or biopsy as the source of disease-specific antigens, and
the patient's own dendritic cells, which are optimized from cells
collected by a single leukapheresis procedure. The proprietary
process uses RNA isolated from the patient's disease sample to
program dendritic cells to target disease-specific antigens. These
activated, antigen-loaded dendritic cells are then formulated with
the patient's plasma, and administered via intradermal injection as
an individualized immunotherapy.
About Argos Therapeutics
Argos Therapeutics is an immuno-oncology company
focused on the development and commercialization of individualized
immunotherapies for the treatment of cancer and infectious diseases
using its Arcelis® technology platform. Argos' most advanced
product candidate, Rocapuldencel-T, is being evaluated in the
pivotal ADAPT Phase 3 clinical trial for the treatment of
metastatic renal cell carcinoma (mRCC). In addition,
Rocapuldencel-T is being studied in a Phase 2
investigator-initiated clinical trial as neoadjuvant therapy for
renal cell carcinoma (RCC). Argos is also developing a separate
Arcelis®-based product candidate, AGS-004, for the treatment of
human immunodeficiency virus (HIV), which is currently being
evaluated in an investigator-initiated Phase 2 clinical trial aimed
at HIV eradication in adult patients.
Forward Looking Statements
Any statements in this press release about
Argos' future expectations, plans and prospects, including
statements about the ADAPT trial and the interim data from the
trial, Argos' anticipated meeting with the FDA, clinical
development of Argos' product candidates and future expectations
and plans and prospects for Argos and other statements containing
the words "believes," "anticipates," "estimates," "expects,"
"intends," "plans," "predicts," "projects," "targets," "may,"
"potential," "will," "would," "could," "should," "continue," and
similar expressions, constitute forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of
1995. Actual results may differ materially from those
indicated by such forward-looking statements as a result of various
important factors, including whether Argos' cash resources will be
sufficient to fund its continuing operations for the periods
anticipated and through completion of the trial; the impact
of the planned analysis of the data and discussions with the
FDA on the development of rocapuldencel-T; the impact of the
recommendation of the IDMC on the continuation of the ADAPT trial;
whether preliminary or interim clinical data such as the interim
data reported in this release will be indicative of the final data
from a clinical trial; whether results obtained in clinical trials
will be indicative of results obtained in future clinical trials;
whether Argos' product candidates will advance through the clinical
trial process on a timely basis; whether the results of such trials
will warrant submission for approval from the United States Food
and Drug Administration or equivalent foreign regulatory
agencies; whether Argos' product candidates will receive
approval from regulatory agencies on a timely basis or at all;
whether, if product candidates obtain approval, they will be
successfully distributed and marketed; whether Argos can
successfully establish commercial manufacturing operations on a
timely basis or at all; and other factors discussed in the "Risk
Factors" section of Argos' Form 10-K for the year ended December
31, 2016, which is on file with the SEC, and in other filings Argos
makes with the SEC from time to time. In addition, the
forward-looking statements included in this press release represent
Argos' views as of the date hereof. Argos anticipates that
subsequent events and developments will cause Argos' views to
change. However, while Argos may elect to update these
forward-looking statements at some point in the future, Argos
specifically disclaims any obligation to do so. These
forward-looking statements should not be relied upon as
representing Argos' views as of any date subsequent to the date
hereof.
Media and investor contact:
Richard Katz, MD, MBA
Argos Therapeutics, Inc.
919-908-0687
rkatz@argostherapeutics.com