AIM ImmunoTech
Announces Publication of Positive Results from Phase 1/2 Study of
Intraperitoneal Chemo-Immunotherapy in Advanced Recurrent Ovarian Cancer
Chemokine-modulating IP chemo-immunotherapy
combination demonstrated to be well tolerated, and associated with
interferon stimulated gene changes that favor cytotoxic T lymphocytes
chemoattraction and function
Strength of data support advancement into Phase 2 clinical study
Phase
2 study will be conducted to evaluate immunologic and clinical efficacy
of tumor loaded αDC1 vaccine in conjunction with the
cisplatin/chemokine modulatory combination regimen
OCALA, Fla., Jan. 24, 2022 (GLOBE NEWSWIRE) -- AIM ImmunoTech Inc. (NYSE: American AIM) (“AIM”
or the “Company”), an immuno-pharma company focused on the research and
development of therapeutics to treat multiple types of cancers, immune
disorders, and viral diseases, including COVID-19, the disease caused by
the SARS-CoV-2 virus, today announced the publication of positive data
from a Phase 1/2 study of intraperitoneal chemo-immunotherapy in
advanced recurrent ovarian cancer. The manuscript titled, “Phase
I trial combining chemokine-targeting with loco-regional
chemo-immunotherapy for recurrent, platinum-sensitive ovarian cancer
shows induction of CXCR3 ligands and markers of type 1 immunity1” was published in the American Association for Cancer Research publication, Clinical Cancer Research.
The
Phase 1/2 study being conducted by the University of Pittsburgh School
of Medicine is designed to evaluate the immunologic and potential
clinical effectiveness of intensive locoregional sequential
intraperitoneal (IP) cisplatin (IPC) with intravenous (iv) paclitaxel
followed by peritoneal infusion of a chemokine modulatory (CKM) regimen
composed of a cocktail of IP rintatolimod and interferon-alpha (IFNα)
for patients with advanced stage ovarian cancer (III-IV) at primary
neoadjuvant setting. AIM ImmunoTech provided rintatolimod (Ampligen®, a dsRNA acting as TLR3 agonist), for the Phase 1/2 study.
“These
results represent an important extension of prior studies using human
tumor explants that showed Ampligen’s potentially important role as a
TLR3 agonist acting synergistically with high-dose IFNα and celecoxib to
selectively enhance Teff cell-attractants while suppressing
Treg-attractants in the tumor microenvironment with a concomitant
increase in the Teff/Treg ratio. This current study shows that similar
findings are seen combining Ampligen with chemokine-targeting and
chemo-immunotherapy in patients being treated for recurrent ovarian
cancer. The importance of boosting the Teff/Treg ratio in the tumor
microenvironment is that it is associated with the conversion of ‘cold’
tumors into ‘hot’ tumors, which have an increased sensitivity to
chemo-immunotherapy and an improved chance of showing tumor regression.
This, of course, creates the potential for a positive survival
advantage,” stated David Strayer, MD, Chief Medical Officer, Chief
Scientific Officer of the Company and Board Certified in Medical
Oncology.
Thomas Equels, Chief Executive Officer of AIM commented, “We are very pleased with these results. Ampligen®
has demonstrated broad immunological effects and we believe has the
potential to be a key component in the treatment of ovarian cancer. We
are grateful to the University of Pittsburg School of Medicine and are
excited to provide support for a larger Phase 2 study which we believe
has the potential to provide hope for patients and their families, as
well as drive significant shareholder value.”
Twelve patients were enrolled in Phase 1 portion of the trial and were treated with IP cisplatin, IP Ampligen®,
and oral celecoxib (COX-2 blocker). Patients in cohorts 2, 3 and 4 also
received IP IFNα at 2, 6 and 18 million units, respectively. The
primary objectives of the study were to evaluate safety, identify Phase 2
recommended dose and characterize changes in the immune TME. Peritoneal
resident cells and IP wash fluid were profiled via NanoString and Meso
Scale Discovery (MSD) multiplex assay, respectively.
Of the 12
patients enrolled in this Phase 1 trial, 9 (75%) were evaluable for
safety, toxicity, and other endpoints. The 3 non-evaluable patients did
not complete at least 3 cycles, due to platinum hypersensitivity
reactions or port complications. Overall, the regimen was well
tolerated, apart from the highest dose of IFNα. Most common toxicities
for all grades were anemia (58%), hypomagnesemia (50%), hyponatremia
(41.7%), arthralgia (41.7%), and fatigue (41.7%). There was one grade 4
hypomagnesemia (8.3%). Dose limiting toxicities of abdominal pain of
grade 3 or more were noted in two patients who received 18MU IFNα
(cohort 4).
The Phase 2 recommended dose of IFNα
was 6 million units every 3 weeks. Median PFS was 8.4 (3-16.4) months.
Median overall survival was 30 (8-66) months. The Company believes these
survival outcome data provide an encouraging early signal. Overall
response rate was 55.6% and the disease control rate (DCR) was 77.8%,
consistent with the expected platinum-sensitive response. Among
responders, median duration of response was 11.7 (6-16.4) months.
Key Results Highlights
Determination
of the safety profile and identification of Phase 2 recommended dose
for the combination of local cisplatin, Ampligen and IFNα, with oral
celecoxib;
Chemo-immunotherapy
combination triggers robust transcriptomic changes in peritoneal
resident cells obtained in longitudinal sampling via IP washes;
Protein content of IP wash fluid captures treatment-induced increases of IFN-induced immune effector molecules; and
Tumor
immune profile at interval debulking shows partial overlap with IP
wash, and points to upregulation of genes encoding for perforin and
granzyme B.
Longitudinal sampling of the
peritoneal cavity via IP washes demonstrated local upregulation of
interferon-stimulated genes, including CTL-attracting chemokines
(CXCL-9, -10, -11), MHC I/II, perforin and granzymes. These changes were
present two days post chemokine modulation and subsided within one
week.
“Epithelial ovarian cancer, the most
common form of ovarian cancer, is the most aggressive gynecologic cancer
and despite aggressive surgery and chemotherapy treatment options, the
5-year survival rate for patients with advanced high grade serous
ovarian cancer remains low. I am very encouraged by the results from
this study. With our growing body of positive data, I look forward to
further advancing development of this important program with the hope of
addressing the significant unmet medical need,” added Robert P. Edwards
MD, Milton McCall Professor and Chairman, Department of Obstetrics,
Gynecology, and Reproductive Sciences, University of Pittsburgh School
of Medicine, Director of Women’s Health for UPMC.
Based
on these encouraging results, the Company plans on supporting a
follow-up Phase 2 trial that will specifically define the immunologic
and clinical efficacy of tumor loaded αDC1 vaccine in conjunction with
the cisplatin/chemokine modulatory combination regimen will be
conducted.
For more information about the Phase 1/2 study, please visit clinicaltrials.gov and reference identifier NCT02432378.
About AIM ImmunoTech Inc.
AIM
ImmunoTech Inc. is an immuno-pharma company focused on the research and
development of therapeutics to treat multiple types of cancers, immune
disorders, and viral diseases, including COVID-19, the disease caused by
the SARS-CoV-2 virus.
This
press release contains forward-looking statements within the meaning of
the Private Securities Litigation Reform Act of 1995 (the “PSLRA”).
Words such as “may,” “will,” “expect,” “plan,” “anticipate” and similar
expressions (as well as other words or expressions referencing future
events or circumstances) are intended to identify forward-looking
statements. Many of these forward-looking statements involve a number of
risks and uncertainties. Among other things, for those statements, the
Company claims the protection of safe harbor for forward-looking
statements contained in the PSLRA. While the Company believes that the
results of the Phase 1/2 study of intraperitoneal chemo-immunotherapy in
advanced recurrent ovarian cancer were positive, significant additional
testing will be required. No assurances can be given as to whether any
studies will be successful or yield favorable data. Additionally,
studies and trials are subject to many factors including lack of
regulatory approval(s), lack of study drug, or a change in priorities at
the institutions sponsoring other trials. There is also the potential
for delays in clinical trial enrollment and reporting because of the
COVID-19 medical emergency. The Company does not undertake to update any
of these forward-looking statements to reflect events or circumstances
that occur after the date hereof.
BioFlorida is the voice of Florida's life sciences industry, representing 8,600 establishments and research organizations in the BioPharma, MedTech, Digital Health and Health Systems that collectively employ nearly 107,000 Floridians. Source: TEConomy/BIO (released 2022)
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