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 on an update on the interim
analysis of data from the ongoing Phase 3 ADAPT clinical trial
evaluating Rocapuldencel-T for the treatment of metastatic renal
cell carcinoma (mRCC) that was presented on September 11, 2017 by
Robert Figlin, MD, Professor and Chairman, Division of Hematology
and Oncology at Cedars Sinai Medical Center, and co-principal
investigator of the ADAPT trial at the European Society for Medical
Oncology (ESMO) 2017 Congress in Madrid, Spain.
A total of 462 patients with previously
untreated advanced or metastatic renal cell carcinoma were enrolled
in the ADAPT trial and randomized 2:1 between combination treatment
with Rocapuldencel-T and sunitinib (combination arm) vs. sunitinib
monotherapy (control arm) after undergoing cytoreductive
nephrectomy.
As previously reported, as of February 3, 2017,
the cut-off date for the most recent interim analysis which was
conducted in February 2017, 42.7% of the 307 patients in the
combination arm demonstrated an objective response by RECIST
criteria, a secondary endpoint in the trial, as compared with 39.4%
of the 155 patients in the control arm. Additional data from the
trial reported for the first time at the ESMO Conference included
data related to the duration of tumor response. Patients in the
combination treatment arm who demonstrated an objective response
had a median duration of response of 8.4 months compared to 6.3
months for patients in the control arm. Additionally, 16% of those
patients with an objective response in the combination treatment
arm had durable responses lasting at least 30 months compared to 7%
of those who had an objective response in the control arm. Also of
note, as of the date of the interim analysis, all of the patients
in the combination arm who had achieved a duration of response of
at least 30 months had maintained those responses through 36
months.
In addition, Dr. Figlin updated immune response
data that had been previously reported by the Company, presenting
data on 117 patients analyzed for immune response. Samples were
collected from patients in the combination arm enrolled at US sites
who provided consent for immune monitoring. Of the 117 patients for
whom this analysis was completed, 96 (82%) 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=83).
Commenting on the data, Dr. Figlin noted,
“Although we did not see a benefit in median overall survival at
the February 2017 interim analysis, the data set was relatively
immature, with over half of the subjects in both treatment arms
still alive. Additionally, for an immunotherapy agent such as
Rocapuldencel-T, one might reasonably expect to see a delayed
treatment effect, as evidenced by the fact that a statistically
significant correlation of the immune response with survival did
not emerge until patients had received at least seven doses of
Rocapuldencel-T. Thus, median overall survival and other
traditional measures of efficacy such as progression-free survival
and objective response rate may not be the best endpoints for
evaluating the potential benefit of this therapy for patients with
limited treatment options, especially in light of the favorable
safety and tolerability profile demonstrated to date. Instead, it
may be more appropriate to evaluate this agent in light of the
potential for a significant “tail-of-the-curve” effect. Thus, my
co-principal investigator and I support Argos’ decision to continue
the ADAPT trial, and we look forward to reviewing a more mature
data set at the next interim analysis, currently planned for the
first half of 2018.”
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 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 reported today.
Following the IDMC 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.
Dr. Figlin’s complete presentation at the ESMO
2017 Congress is available for review on Argos’ website at
www.argostherapeutics.com. Argos plans to hold a conference call to
discuss Dr. Figlin’s presentation on Wednesday, September 20th at
4:30pm ET and will provide logistical information in a subsequent
announcement.
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 combination with vorinostat, a latency-reversing drug,
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 the ADAPT trial and the interim data from the
trial, the 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 period
anticipated; whether preliminary or interim clinical data such as
the data presented 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 June 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