Corvus Pharmaceuticals Announces New Data Highlighting Potential of Ciforadenant to Overcome Immunotherapy Resistance in Metastatic Castration Resistant Prostate Cancer
November 09 2024 - 1:40PM
Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage
biopharmaceutical company, today announced new data highlighting
the potential of ciforadenant, the Company’s adenosine A2A receptor
antagonist, to overcome resistance to anti-PD1 immunotherapy in the
treatment of metastatic castration resistant prostate cancer
(mCRPC).
The data were presented today in an oral session at the Society
for Immunotherapy of Cancer (SITC) 39th Annual Meeting
by Aram Lyu, Ph.D., a postdoctoral fellow at Fred Hutch Cancer
Center, University of California, San Francisco and Parker Scholar
at the Parker Institute for Cancer Immunotherapy. Dr. Lyu’s
abstract, titled “Identification and therapeutic target of
myeloid-mediated mechanisms of immunotherapy resistance in prostate
cancer” was selected as a Top 100 abstract by SITC.
“These studies reveal important details on the role of the
adenosine pathway on the immunobiology of mCRPC, including the
importance of myeloid cells and the adenosine gene signature,” said
Richard A. Miller, M.D., co-founder, president and chief executive
officer of Corvus. “The mechanism is consistent with and builds on
results from our clinical trials in renal cell cancer and prostate
cancer, along with the potential for the adenosine gene signature
to select patients most likely to respond. This could be an
important advancement for patients with tumors that are resistant
to checkpoint inhibitors, and is supportive of our ongoing clinical
trial of ciforadenant in combination with ipilimumab and nivolumab
in front line renal cell cancer.”
SITC Oral Presentation Overview and Key
DataPrevious studies have shown that mCRPC is resistant to
therapy with immune checkpoint inhibitors. While tumor associated
macrophages are known to contribute to immunosuppression with the
tumor microenvironment, this study identified SPP1+ myeloid cells
as a potential critical mediator of resistance to immunotherapy.
The team led by Lawrence Fong, M.D. used single cell RNA expression
profiling of tumor biopsies to measure levels of these cells in
patients with early localized or metastatic hormone responsive
prostate cancer compared to patients with mCRPC. The results showed
that SPP1+ macrophages were more prevalent as cancer progresses to
mCRPC patients.
Dr. Fong is the scientific director of the Immunotherapy
Integrated Research Center at Fred Hutch, where he is also a
professor in the Translational Sciences and Therapeutics Division
and a Bezos Family Distinguished Scholar in Immunotherapy.
The researchers created a murine model that confirmed that SPP1+
macrophages were associated with suppressed immunity to prostate
cancer and shortened overall survival. Further analysis of the
related genetic pathways revealed involvement of adenosine
signaling through the adenosine 2A receptor. The researchers
utilized ciforadenant to inhibit adenosine signaling in this model
and the key findings demonstrating its potential to overcome this
resistance to immunotherapy include:
- Ciforadenant treatment associated with reduced
immunosuppression and enhanced sensitivity to anti-PD1 therapy in
the model
- Ciforadenant treatment associated with reduced SPP1+ macrophage
infiltration in the tumors, supporting a shift to a less
immunosuppressive myeloid environment
- The Adenosine Gene Signature, a biomarker that reflects
adenosine induced immunosuppression in the tumor, was elevated in
SPP1+ macrophages
- Results from the model were consistent with data from the Phase
1b/2 clinical trial of ciforadenant in patients with mCRPC, which
included data from 35 patients with advanced mCRPC, including 11
who received ciforadenant as a monotherapy (100 mg twice daily) and
24 that received ciforadenant (100 mg twice daily) in combination
with atezolizumab (840 mg delivered intravenously every two
weeks). 5 of 24 (21%) receiving combination therapy had PSA
partial responses defined as PSA reductions >30%, compared to 1
of 11 (9%) receiving monotherapy
About Corvus PharmaceuticalsCorvus
Pharmaceuticals is a clinical-stage biopharmaceutical company
pioneering the development of ITK inhibition as a new approach to
immunotherapy for a broad range of cancer and immune diseases. The
Company’s lead product candidate is soquelitinib, an
investigational, oral, small molecule drug that selectively
inhibits ITK. Its other clinical-stage candidates are being
developed for a variety of cancer indications. For more
information, visit www.corvuspharma.com.
About CiforadenantCiforadenant (CPI-444) is an
investigational small molecule, oral, checkpoint inhibitor designed
to disable a tumor’s ability to subvert attack by the immune system
by blocking the binding of adenosine to immune cells present in the
tumor microenvironment. Adenosine, a metabolite of ATP (adenosine
tri-phosphate), is produced within the tumor microenvironment where
it may bind to the adenosine A2a receptor present on immune cells
and block their activity. Ciforadenant has been shown to block the
immunosuppressive effects of myeloid cells present in tumors and
preclinical studies published in 2018 demonstrated synergy with
combinations of anti PD1 and anti-CTLA4 antibodies.
Adenosine Gene SignatureThe adenosine gene
signature is a biomarker that reflects adenosine induced
immunosuppression in the tumor. These genes express chemokines
that recruit myeloid cells including immunosuppressive tumor
associated myeloid cells, which are thought to mediate resistance
to anti-PD-(L)1 treatment.
Forward-Looking StatementsThis press release
contains forward-looking statements, including statements related
to the potential efficacy of the Company’s product candidates
including ciforadenant; the potential use of ciforadenant to treat
metastatic renal cell cancer and mCRPC, including the potential to
overcome resistance to immunotherapy; and the potential for the
adenosine gene signature to select patients most likely to respond
to treatment. All statements other than statements of historical
fact contained in this press release are forward-looking
statements. These statements often include words such as “believe,”
“expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,”
“will,” “may” or similar expressions. Forward-looking statements
are subject to a number of risks and uncertainties, many of which
involve factors or circumstances that are beyond the Company’s
control. The Company’s actual results could differ materially from
those stated or implied in forward-looking statements due to a
number of factors, including but not limited to risks detailed in
the Company’s Quarterly Report on Form 10-Q for the three months
ended June 30, 2024, filed with the Securities and
Exchange Commission on August 6, 2024, as well as other
documents that may be filed by the Company from time to time with
the Securities and Exchange Commission. In particular, the
following factors, among others, could cause results to differ
materially from those expressed or implied by such forward-looking
statements: the Company’s ability to demonstrate sufficient
evidence of efficacy and safety in its clinical trials of its
product candidates; the accuracy of the Company’s estimates
relating to its ability to initiate and/or complete preclinical
studies and clinical trials and release data from such studies and
clinical trials; the results of preclinical studies and interim
data from clinical trials not being predictive of future results;
the Company’s ability to enroll sufficient numbers of patients in
its clinical trials; the unpredictability of the regulatory
process; regulatory developments in the United States and
other foreign countries; the costs of clinical trials may exceed
expectations; and the Company’s ability to raise additional
capital. Although the Company believes that the expectations
reflected in the forward-looking statements are reasonable, it
cannot guarantee that the events and circumstances reflected in the
forward-looking statements will be achieved or occur, and the
timing of events and circumstances and actual results could differ
materially from those projected in the forward-looking statements.
Accordingly, you should not place undue reliance on these
forward-looking statements. All such statements speak only as of
the date made, and the Company undertakes no obligation to update
or revise publicly any forward-looking statements, whether as a
result of new information, future events or otherwise.
INVESTOR CONTACT:Leiv LeaChief Financial
OfficerCorvus Pharmaceuticals,
Inc.+1-650-900-4522llea@corvuspharma.com
MEDIA CONTACT:Sheryl SeapyReal
Chemistry+1-949-903-4750sseapy@realchemistry.com
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