- Trials are
designed to demonstrate whether the addition of Actimab-A to either
KEYTRUDA® or OPDIVO® can result in improved
patient outcomes
- MDSCs –
Myeloid Derived Suppressor Cells in the tumor microenvironment are
believed to reduce effectiveness of PD-1 inhibitors like
KEYTRUDA® and OPDIVO®
- Trials
supported by preclinical data showing Actimab-A can selectively
target and deplete MDSCs which express CD33
- Clinical
proof of concept data expected in 2025 could potentially open up a
multi-billion-dollar market opportunity for Actimab-A as a
combination therapy with PD-1 inhibitors in multiple solid
tumors
NEW
YORK, March 18, 2025 /PRNewswire/ -- Actinium
Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the
Company), a pioneer in the development of targeted radiotherapies,
today announced a clinical program comprising of trials studying
Actimab-A in combination with either KEYTRUDA®
(pembrolizumab) or OPDIVO® (nivolumab) which are
blockbuster immunotherapies known as PD-1 inhibitors which are
approved in multiple solid tumor indications.
KEYTRUDA® developed and commercialized by Merck &
Co. and OPDIVO® developed and commercialized by Bristol
Myers Squibb, collectively generated $38.8
billion in sales in 2024 across several solid tumor cancer
indications. However, the efficacy of these drugs has shown to be
limited by a certain type of cell known as MDSCs or Myeloid Derived
Suppressor Cells which accumulate in the tumor microenvironment.
MDSCs express the CD33 antigen which is targeted by
Actimab-A. The rationale for studying Actimab-A in
combination with either KEYTRUDA® or
OPDIVO® is based on the premise that depleting MDSCs
with Actimab-A will improve the efficacy of these drugs.
MDSCs are immune-suppressive cells that help tumors evade immune
detection and promote disease progression. They are overexpressed
in the tumor microenvironment in several different solid tumors and
associated with poor outcomes. They work by multiple mechanisms but
most relevant to PD-1 inhibitors which work by keeping T-cells
active is that MDSCs prevent T-cells from recognizing and attacking
cancer cells. There is considerable preclinical scientific evidence
in the literature that depleting MDSCs could be a viable strategy
in improving the outcomes of PD-1 directed immunotherapy, however,
there have been no viable clinical approaches that have been tried
successfully to our knowledge. MDSCs are known to express the
CD33 antigen which is the target of Actimab-A. Actinium has
also generated published and unpublished preclinical data showing
that Actimab-A can selectively deplete MDSCs in solid tumors.
Actinium believes that in the clinic Actimab-A can deplete CD33
expressing MDSCs and hence improve the outcomes with PD-1
inhibitors such as KEYTRUDA® and OPDIVO®.
Actimab-A is Actinium's lead radiotherapeutic that delivers
Actinium-225, a potent alpha-emitter radioisotope payload that can
produce lethal double strand DNA breaks to kill targeted cells.
Actimab-A has been studied in over 150 patients in several clinical
trials in Acute Myeloid Leukemia or AML. Based on its safety
and tolerability, Actimab-A is under clinical development via an
NCI CRADA in the front-line AML setting with an expected
registrational study in combination with CLAG-M in
relapsed/refractory AML expected to initiate in 2025.
The Actimab-A solid tumor program is comprised of several
controlled, head-to-head clinical trials that will evaluate the
combination of Actimab-A with KEYTRUDA® versus
KEYTRUDA® alone, and Actimab-A with
OPDIVO® versus OPDIVO® alone. The
initial tumors that are being targeted are HNSCC or Head and Neck
Squamous Cell Carcinoma and NSCLC or Non-Small Cell Lung Cancer
with a separate trial for each indication. The patient population
for these trials will be adults with PD-L1 expression and locally
advanced metastatic HNSCC or NSCLC randomized to either Actimab-A
alone or Actimab-A with a specific checkpoint inhibitor. The
objective of each trial would be to evaluate the safety and
tolerability as well as following endpoints including ORR – Overall
Response Rate, PFS – Progression Free Survival and OS – Overall
Survival. Further, the following biomarker data would be collected
including the pattern of depletion of CD33+ MDSCs and T-Cell
activity in peripheral blood. Actinium expects to present initial
proof of concept clinical data from the first of these trials in
the second half of 2025 as well as provide an update on the outlook
for the rest of the trials in the Actimab-A solid tumor
program.
Dr. Avinash Desai, Actinium's
Chief Medical Officer, said, "The Actimab-A solid tumor program is
highly novel and has the potential to address the high unmet need
of patients receiving PD-1 checkpoint inhibitors whose cancer stops
responding or progresses. Our preclinical data is highly
encouraging and we believe this novel approach combining Actimab-A
with PD-1 inhibitors has immense potential. We are greatly
enthusiastic about these head-to-head trials, and eager to present
our initial proof-of-concept results by the end of 2025."
Sandesh Seth, Actinium's Chairman
and CEO, said, "We have great enthusiasm for Actimab-A in
combination with PD-1 checkpoint inhibitors given the large
potential addressable patient population. MDSCs are over expressed
in multiple solid tumors giving Actimab-A pan tumor potential in
indications that are treated with checkpoint inhibitors. Per
our initial estimates this represents a treatment population in
excess of 500,000 patients. Together with our efforts in
myeloid malignancies, this is another important program for
Actimab-A. This year, clinical data from Actimab-A as a potential
backbone therapy in radiation sensitive myeloid malignancies, and
in solid tumors in combination with PD-1 checkpoint inhibitors, can
establish its potential to become a leading blockbuster targeted
radiotherapy."
About Actinium Pharmaceuticals, Inc.
Actinium is a pioneer in the development of targeted
radiotherapies intended to meaningfully improve patient outcomes.
Actinium is advancing its lead product candidate Actimab-A, a CD33
targeting therapeutic, as potential backbone therapy in acute
myeloid leukemia (AML) and other myeloid malignancies leveraging
the mutation agnostic alpha-emitter radioisotope payload
Actinium-225 (Ac-225). Actimab-A has demonstrated potential
activity in relapsed and refractory acute myeloid leukemia (r/r
AML) patients in combination with the chemotherapy CLAG-M including
high rates of Complete Remissions (CR) and measurable residual
disease (MRD) negativity leading to improved survival outcomes and
is being advanced to a pivotal Phase 2/3 trial. In addition,
Actinium is engaged with the National Cancer Institute (NCI) under
the Cooperative Research and Development Agreement (CRADA) for
development of Actimab-A in AML and other myeloid malignancies. The
first clinical trial under the CRADA will evaluate the triplet
combination comprised of Actimab-A, Venetoclax (Abbvie/Roche) an
oral Bcl-2 inhibitor and ASTX-727 (Taiho Oncology, an Otsuka
holdings company) a novel oral hypomethylating agent (HMA) in
frontline acute myeloid leukemia (AML) patients. Additionally,
Actinium is developing Actimab-A as a potential pan tumor therapy
in combination with PD-1 checkpoint inhibitors including
KEYTRUDA® and OPDIVO® by depleting myeloid
derived suppressor cells (MDSCs), which represents a potential
multi-billion-dollar addressable market. Iomab-ACT, Actinium's next
generation conditioning candidate, is being developed with the goal
of improving patient access and outcomes for potentially curative
cell and gene therapies. Iomab-B is an induction and conditioning
agent prior to bone marrow transplant in patients with r/r AML,
which Actinium is seeking a potential strategic partner for in the
U.S. In addition, the company's R&D efforts are primarily
focused on advancing several preclinical programs for solid tumor
indications. Actinium holds 230 patents and patent applications
including several patents related to the manufacture of the isotope
Ac-225 in a cyclotron.
For more information, please
visit: https://www.actiniumpharma.com/
Forward-Looking Statements
This press release may contain projections or other
"forward-looking statements" within the meaning of the
"safe-harbor" provisions of the private securities litigation
reform act of 1995 regarding future events or the future financial
performance of the Company which the Company undertakes no
obligation to update. These statements are based on management's
current expectations and are subject to risks and uncertainties
that may cause actual results to differ materially from the
anticipated or estimated future results, including the risks and
uncertainties associated with preliminary study results varying
from final results, estimates of potential markets for drugs under
development, clinical trials, actions by the FDA and other
governmental agencies, regulatory clearances, responses to
regulatory matters, the market demand for and acceptance of
Actinium's products and services, performance of clinical research
organizations and other risks detailed from time to time in
Actinium's filings with the Securities and Exchange Commission (the
"SEC"), including without limitation its most recent annual report
on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms
8-K, each as amended and supplemented from time to time.
Investors:
investorrelations@actiniumpharma.com
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SOURCE Actinium Pharmaceuticals, Inc.
