Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage
biopharmaceutical company focused on the development and
commercialization of precisely targeted oncology therapies with
biomarker patient enrichment selection, today announced updated
results from its Phase 1/1b trial of CPI-006, the Company’s
anti-CD73 antibody. The clinical data continue to support a novel
mechanism of action involving the activation of immune cells
potentially directed against tumors, along with the inhibition of
adenosine production. The results will be presented today in an
oral session at the Society for Immunotherapy of Cancer (SITC)
Annual Meeting in National Harbor, Maryland by Jason
J. Luke, M.D., principal investigator of the trial and Director of
the Cancer Immunotherapeutics Center at UPMC Hillman Cancer
Center and Associate Professor of Medicine at
the University of Pittsburgh School of Medicine.
“As previously reported at ASCO, our clinical studies continue
to demonstrate the novel immunobiological properties of CPI-006,”
said Richard A. Miller, M.D., co-founder, president and chief
executive officer of Corvus. “Based on its ability to activate
various immune cells and inhibit the production of adenosine, we
believe CPI-006 has potential as a monotherapy and combination
medicine for a variety of tumor types. We plan to continue to
enroll cancer patients in the CPI-006 Phase 1/1b study at the
selected dose of 18 mg/kg, which has been well-tolerated to date
and has demonstrated complete occupancy of the target within
tumors. In addition, we continue to develop the Adenosine Gene
Signature, with additional data from a larger number of patients
with renal cell cancer indicating that it could be used as a
biomarker driven patient enrichment strategy in future clinical
trials which would potentially enable us to select patients most
likely to benefit from treatment.”
The CPI-006 Phase 1/1b study is currently enrolling patients
with a variety of cancers who have failed standard therapies. It is
designed to select the dose and evaluate the safety,
pharmacokinetics, immune biomarkers and efficacy of CPI-006 as a
single agent; in combination with ciforadenant (CPI-444), a
selective and potent inhibitor of the adenosine A2A receptor; and
in combination with pembrolizumab, an anti-PD-1 antibody. Once the
optimum dose is identified, pre-specified disease specific
expansion cohorts will enroll patients with metastatic castration
resistant prostate cancer (mCRPC), renal cell cancer (RCC), non
small cell lung cancer (NSCLC) and other cancers. The efficacy
endpoints are complete response (CR), partial response (PR),
disease control rate, duration of response, progression-free
survival and overall survival. Based on the data to-date from the
dose-escalation portion of the study, the Company has selected a
CPI-006 dose of 18 mg/kg every three weeks for continued expansion
in the monotherapy arm of the Phase 1/1b study.
CPI-006 Phase 1/1b Results
at SITC 2019 Today, Dr. Luke will present
updated results from the first two arms of the study, which are
evaluating CPI-006 as a single agent and in combination with
ciforadenant. The presentation includes data from 24 patients who
received CPI-006 given intravenously as monotherapy (at doses of 1,
3, 6, 12, 18 or 24 mg/kg every 21 days) and 16 patients who
received the combination treatment of CPI-006 (1, 3, 6, 12 or 18
mg/kg every 21 days) plus a fixed dose of ciforadenant (100 mg
twice daily). These patients had advanced, refractory disease (12
had colorectal cancer, six had renal cell cancer, six had
pancreatic cancer, six had prostate cancer, five had head and neck
cancer, three had non-small cell lung cancer, one had bladder
cancer and one had sarcoma), and had failed a median of four prior
therapies. The key highlights from the CPI-006 clinical results
include:
- Pharmacokinetic studies showed a dose-dependent increase in
CPI-006 plasma exposure, with doses of 6 mg/kg and higher producing
sustained plasma levels of CPI-006 and doses of 12 mg/kg and higher
achieving complete and sustained occupancy of CD73 on peripheral
blood lymphocytes.
- Biopsies revealed penetration of CPI-006 and complete occupancy
of CD73 in tumors at doses of 18 mg/kg, which is the selected dose
for continued expansion of the study. In vitro results
revealed that CPI-006 induced B-cell differentiation into both
plasmablasts and memory B-cells, promoted secretion of
immunoglobulin M (IgM), and class switching of the IgM to produce
immunoglobulin G (IgG).
- In vivo results demonstrated that treatment with CPI-006
produced changes in blood B-cell and T-cell levels, highlighted by
a reduction in circulating B-cells within 30 minutes of treatment,
with a partial return by 21 days, and with returning B-cell levels
heavily enriched with memory B-cells. These changes are
consistent with the in vitro findings that suggest that CPI-006
induces a humoral adaptive immune response.
- A specific analysis of the B-cell receptor repertoire (the
range of B-cell receptors expressed by the total B-cell population)
revealed that several patients exhibited the induction of new
memory B-cell clones in blood following treatment with
CPI-006, with clonal frequencies as high as 1%, supporting a very
strong antibody immune response comparable or exceeding that seen
when patients receive vaccinations. These findings are consistent
with antigen driven clonal expansion of B-cells.
- In evaluable patients receiving 6 mg/kg and higher in the
protocol defined, pre-specified disease specific cohorts, tumor
regression was seen in four of nine patients: mCRPC (one of two
patients; reduction of 18.2%), RCC (two of five patients; reduction
of 7.0%, 21.3%) and NSCLC (one of two patients; reduction of
5.8%).
- A patient with metastatic prostate cancer that had previously
failed multiple anti-androgen therapies and chemotherapy received
over 19 cycles (a cycle equals 21 days) of CPI-006 monotherapy at a
dose of 6 mg/kg and showed reduction in tumor volume and a
reduction in bone pain.
- CPI-006 was well tolerated at all dose levels, with no
dose-limiting toxicities. Grade 1 infusion reactions were detected
(N=3 patients) and mitigated with premedication with acetaminophen
and antihistamine. Grade 3 or 4 toxicities included a grade 3
anemia (N=1) and a grade 3/4 diarrhea (N=1).
“CPI-006 is an anti-CD73 antibody that has powerful
immunomodulatory effects,” said Dr. Luke. “Its in vivo effects are
rapid and include the redistribution of B-cells and T-cells, with
returning B-cells demonstrating a phenotype that indicates
sensitization with antigen. Our B-cell receptor studies
demonstrated selective clonal expansion to antigens suggesting that
CPI-006 may be eliciting an anti-cancer immune response. To-date,
this has been supported in patients, some of whom have observed
tumor regression when treated with monotherapy or in combination
with ciforadenant.”
Adenosine Gene Signature Data at SITC
2019Updated data on the Adenosine Gene Signature will be
presented today in a poster session at the SITC Annual Meeting
by Stephen Willingham, PhD, Corvus Senior Scientist. The key
highlights from the poster include:
- The Adenosine Gene Signature was examined in 32 patients with
advanced refractory renal cell cancer, including 21 that were
positive for this biomarker and 11 that were negative for this
biomarker. In patients with a positive biomarker result, 17% had a
partial response (PR) and many had tumor regression that did not
meet the response evaluation criteria in solid tumors (RECIST) for
PR. In patients with a negative biomarker result, there were no
responses. In the 21 patients in the Adenosine Gene Signature
positive group, 9 patients had tumor regression; 4 patients had no
change in tumor size; and 8 patients had tumor progression as best
response; no patients in the negative group showed tumor
reduction. There was a statistically significant correlation
of the Adenosine Gene Signature with tumor response, p=0.008.
- A positive Adenosine Gene Signature was also associated with
duration of response. Six of 21 patients had progression free
survival (PFS) exceeding 40 weeks, with a plateau on the curve, and
all of these patients were Adenosine Gene Signature positive,
including four patients who had failed prior therapies with anti
PD(L)-1.
- CPI-006 blocks CD73 enzymatic activity and prevents conversion
of adenosine monophosphate (AMP) to adenosine leading to an
elevation of AMP levels.
- AMP induces gene expression changes nearly identical to the
Adenosine Gene Signature due to its ability to bind to and activate
the adenosine A2A receptor, producing similar effects to that of
adenosine binding to the A2A receptor.
- CD73 antagonists preserve AMP and thereby amplify the AMP gene
expression signature.
- Ciforadenant (which has been shown to inhibit adenosine binding
to A2A receptor) blocks both AMP and adenosine induced gene
expression changes.
- This suggests that use of CPI-006 (which has been shown to
inhibit adenosine production) in combination with ciforadenant
could be a more effective way to block the immunosuppressive
effects of A2A receptor signaling.
“We continue to confirm the predictive value of the Adenosine
Gene Signature in patients with renal cell cancer,” said Dr.
Willingham. “Patients with this biomarker have been more likely to
respond to adenosine blockade with ciforadenant and we intend to
use this biomarker driven enrichment strategy in our future studies
with ciforadenant and CPI-006.”
SITC Investor and Analyst ReceptionCorvus will
host an investor and analyst reception today, November 8, 2019, at
6:00 pm ET, to discuss both the CPI-006 data and the Adenosine Gene
Signature data presented at SITC 2019. The reception will feature
Dr. Luke, Dr. Miller, and members of the scientific and clinical
staff at Corvus. The company will offer a live webcast of the
reception, which can be accessed via the investor relations section
of the Corvus website. A replay of the webcast will be available on
Corvus' website for one year.
About Corvus Pharmaceuticals Corvus
Pharmaceuticals is a clinical-stage biopharmaceutical company
focused on the development and commercialization of precisely
targeted oncology therapies. Corvus’ lead product candidates are
ciforadenant (CPI-444), a small molecule inhibitor of the A2A
receptor, and CPI-006, a humanized monoclonal antibody directed
against CD73 that exhibits immunomodulatory activity and blockade
of adenosine production. These product candidates are being studied
in ongoing Phase 1 and 2 clinical trials in patients with a wide
range of advanced solid tumors. Ciforadenant is being evaluated in
a successive expansion cohort trial examining its activity both as
a single agent and in combination with an anti-PD-L1 antibody.
CPI-006 is being evaluated in a multicenter Phase 1/1b clinical
trial as a single agent, in combination with ciforadenant, and in
combination with pembrolizumab. The Company’s third clinical
program, CPI-818, an oral, small molecule drug that has been shown
to selectively inhibit ITK, is in a multicenter Phase 1/1b clinical
trial in patients with several types of T-cell lymphomas. For more
information, visit www.corvuspharma.com.
About CPI-006CPI-006 is a potent humanized
monoclonal antibody that reacts with the active site of CD73,
blocking the conversion of AMP to adenosine. This antibody also
possesses immunomodulatory activity resulting in activation of
lymphocytes and effects on lymphocyte trafficking, which are
independent of adenosine. In vitro studies of CPI-006 have
shown it is capable of substantially inhibiting the production of
adenosine by blocking the CD73 enzyme.
About Ciforadenant Ciforadenant (CPI-444) is a
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 in the tumor microenvironment to the A2A
receptor. 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. CD39 and CD73 are enzymes on the surface of tumor cells
and immune cells. These enzymes work in concert to convert ATP to
adenosine. In vitro and preclinical studies have shown that dual
blockade of CD73 and the A2A receptor may be synergistic.
Forward-Looking Statements This press release
contains forward-looking statements, including statements related
to the potential safety and efficacy of CPI-006 and ciforadenant,
the Company’s ability to develop and advance product candidates
into and successfully complete preclinical studies and clinical
trials, including the Company’s Phase 1/1b clinical trial of
ciforadenant, and the Company’s Phase 1/1b clinical trial of
CPI-006, the utility of biomarker data collected and the
suitability of dosing regimen selected for clinical trials and the
potential utility of the Adenosine Gene Signature to identify
patients that are most likely to respond to therapies targeting the
adenosine pathway. 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 quarter ended
September 30, 2019, filed with the Securities and Exchange
Commission on October 29, 2019, 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
accuracy of the Company’s estimates relating to its ability to
initiate and/or complete clinical trials; the Company’s ability to
demonstrate sufficient evidence of efficacy and safety in its
clinical trials of ciforadenant and CPI-006; the Company’s ability
to utilize biomarker data and select suitable dosing regimens; the
Adenosine Gene Signature may not prove to be useful; the results of
preclinical studies may not be predictive of future results; the
unpredictability of the regulatory process; and regulatory
developments in the United States and foreign countries. 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 SeapyW2O pure+1
213-262-9390sseapy@purecommunications.com
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