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 provided an update on the immunology
data from the February 2017 interim analysis of data from the
ongoing Phase 3 ADAPT clinical trial evaluating Rocapuldencel-T for
the treatment of metastatic renal cell carcinoma (mRCC) presented
in the poster session at the 32nd Annual Meeting of the Society for
Immunotherapy of Cancer (SITC) in National Harbor, Maryland. The
presentation is focused primarily upon immunology data from the
ADAPT clinical trial and includes both new data and an update to
data that was previously presented at the European Society of
Medical Oncology Conference in September 2017 that now includes
additional patients.
As background, 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).
Immunology data from the February 2017 interim
analysis of the data from the ADAPT study reported at the SITC
Conference were pre-specified and include correlations between
survival and (i) the change from baseline in antigen-specific
memory T-cells, (ii) the amount of IL-12 secreted by each patient’s
specific Rocapuldencel-T immunotherapy, and (iii) the percentage of
regulatory T-cells at baseline, which was observed in both arms of
the study. Of note, data for antigen-specific memory T-cells and
regulatory T-cells were available only for patients enrolled at
North American sites.
Increase from Baseline in Antigen-Specific
Memory T-Cells
In subjects for whom immune response data were
analyzed (n=146), the number of antigen-specific memory T-cells was
found to increase only after administration of Rocapuldencel-T. In
those subjects who received at least seven doses of Rocapuldencel-T
(n=100), the average number of antigen-specific memory T-cells
after the seventh dose was approximately double the number observed
before treatment. This increase was found to be statistically
significant (p<0.0001). Similar data on a smaller number of
patients were presented at the European Society for Medical
Oncology Conference in September 2017.
Additionally, for those subjects who received at
least seven doses of Rocapuldencel-T, there was a statistically
significant correlation between survival and the change in the
number of antigen-specific memory T-cells from baseline (Spearman’s
Rho = 0.40; p<0.0001). For those 25 patients with the greatest
increase in the number of antigen-specific memory T-cells from
baseline, no patient deaths had been recorded as of the time of the
February 2017 interim analysis.
IL-12 Secretion by Each Patient’s Specific
Rocapuldencel-T Immunotherapy
An analysis was conducted to evaluate the
relationship between the amount of IL-12 secreted by each patient’s
specific immunotherapy and that patient’s survival. Samples from
patients treated with Rocapuldencel-T as of February 2017 (n=179)
were divided into two groups: those with above the median amount of
IL-12, and those with below the median amount of IL-12. Comparison
of the Kaplan-Meier curves for these two groups revealed that those
with higher than median levels of IL-12 demonstrated improved
survival. Additionally, there was a statistically significant
correlation between the level of IL-12 and survival (Spearman’s Rho
= 0.27; p<0.0002). There was also a statistically significant
correlation between the level of IL-12 and the change from baseline
in antigen-specific memory T-cells for patients who received at
least seven doses of Rocapuldencel-T (n=95; Spearman’s Rho = 0.43;
p<0.0001).
Regulatory T-Cells
An analysis was conducted to evaluate the
relationship between the percentage of regulatory T-cells at
baseline and survival for patients in both arms of the trial.
Samples from patients in the combination arm (n=176) were divided
into two groups: those with above median percentage of regulatory
T-cells at baseline, and those with below median percentage of
regulatory T-cells at baseline. Comparison of the Kaplan-Meier
curves for these two groups revealed that those with higher than
median percentage of regulatory T-cells at baseline demonstrated
improved survival. This finding was in contrast to the control arm
(n=79), where a greater percentage of regulatory T-cells at
baseline was associated with poorer survival. One hypothesis that
could potentially explain this result is that Rocapuldencel-T may
be acting to convert regulatory T-cells to effector T-cells.
Commenting on the additional immunology data,
Charles Nicolette, Chief Scientific Officer of Argos Therapeutics,
noted, “As we have conducted additional analyses of the immunology
data from the February 2017 interim analysis, we have been pleased
to see that the data are generally supportive of our hypothesis
regarding the intended mechanism of action of Rocapuldencel-T to
induce an immune response against the tumor in patients with
metastatic renal cell carcinoma. While we await further data from
the next planned interim data analysis that we expect to be
conducted during the first half of 2018, pending agreement with the
FDA on a revised protocol that we plan to submit, we are encouraged
to see these positive indicators of activity.”
As previously reported, the February 2017
interim analysis was conducted by the ADAPT trial's Independent
Data Monitoring Committee (IDMC) after 75% of the originally
targeted number of 290 events (deaths) for the analysis of the
primary endpoint of overall survival had occurred. At the time of
the analysis, with more than half of the patients still alive in
each arm and a median follow-up time of ~20 months, the IDMC
concluded that the trial was unlikely to demonstrate a
statistically significant improvement in median overall survival in
the combination arm and recommended that the trial be discontinued
for futility. However, the ADAPT trial principal investigators and
Argos considered the data too immature to observe the delayed
effects typically associated with immunotherapy and decided to
continue the trial pending further review and analysis of the data
and discussions with the U.S. Food and Drug Administration (FDA).
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 a
long-term memory immune response, and the IDMC's assessment of the
safety profile of Rocapuldencel-T. This determination was
subsequently further supported by the extended durability of tumor
responses in the combination arm, as previously reported.
Following the IDMC’s interim analysis, the
Company met with the FDA to discuss the ADAPT trial and the future
direction of the Rocapuldencel-T program in April 2017. The FDA
agreed with the Company's decision to continue the ADAPT trial, and
further agreed to review a protocol amendment to extend the trial
beyond the originally targeted 290 events and a revised statistical
analysis plan that the Company plans to submit.
Conference Call Information
Argos will hold a conference call to discuss the
data presented at the 32nd Annual Meeting of the Society for
Immunotherapy of Cancer on Monday, November 13th at 8:30am ET. To
participate by telephone, please dial (855) 433-0930 (Domestic) or
(484) 756-4271 (International). The conference ID number is
9396519. Slides setting forth the data presented at the SITC 2017
Annual Meeting, and a live and archived audio webcast, will be
accessible through the Investors section of the Company's website
at www.argostherapeutics.com. The archived webcast will remain
available on the Company's website for twelve (12) months following
the call.
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). 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. Funding for the
development of AGS-004 has been provided by the National Institutes
of Health, the National Institute of Allergy and Infectious
Diseases, and the Collaboratory of Research for AIDS
Eradication.
Forward Looking Statements
Any statements in this press release about
Argos' future expectations, plans and prospects, including
statements about Argos’ financial prospects, future operations and
sufficiency of funds for future operations, clinical development of
Argos' product candidates, expectations regarding future clinical
trials and FDA activities 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 period
anticipated; whether preliminary or interim clinical data, such as
the data referenced 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-Q for the quarter ended
September 30, 2017, 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.
Investor contact: Richard Katz, MD, MBAChief
Financial Officer Argos Therapeutics, Inc. 919-287-6315
rkatz@argostherapeutics.com
Media Contact:Adam DaleyBerry & Company
Public Relations212.253.8881adaley@berrypr.com