Preliminary Analysis Supports the Ability of Immunovaccine’s Lead Candidate to Induce T-Cell Infiltration
Early Data Reflect Tolerability and Clinical Potential of the Triple Combination Immunotherapy in Recurrent Ovarian Cancer
Immunovaccine Inc. (“Immunovaccine” or the “Company”) (TSX:IMV)
(OTCQX:IMMVF), a clinical stage vaccine and immunotherapy company, today
announced the first interim data analysis from its ongoing Phase 1b clinical study
of its novel T-cell activating immuno-oncology candidate, DPX-Survivac,
in combination with epacadostat and low-dose cyclophosphamide. The
analysis included the results of blood tests, tumor biopsies and CT
scans to assess safety, disease progression and T-cell response for the
first four evaluable patients in the trial.
All patients enrolled in the trial have recurrent ovarian
cancer with evidence of progressive disease. Based on the interim
analysis, the combination therapy appears to have an acceptable safety
profile, with a single grade 3 and single grade 4 event reported and no
serious adverse events (SAEs) reported.
At the time of the interim analysis, three of four patients
exhibited stable disease, while a fourth patient continued to progress
and discontinued the trial. In addition, researchers observed:
- Signs of increased T cell activity in tumors in three of the four patients based on RNA sequencing
- Stable disease with signs of tumor shrinkage in the
patient who has been in trial for the longest duration thus far (based
on CT scan at day 140)
“We are very encouraged by these early data, which are
tremendously important to Immunovaccine, as they help to validate the
underlying clinical potential of DPX-Survivac,” said Frederic Ors, Immunovaccine’s Chief Executive Officer. “Research is consistently demonstrating that activating T cells is a crucial mechanism to improving tumor response ratesi.
This desired mechanism of action is exactly what we have developed
DPX-Survivac to address, and this data set has provided an encouraging
first clinical demonstration of this effect.”
Immunovaccine is developing DPX-Survivac as a combination
therapy that can significantly expand the range of cancers successfully
treatable by novel immunotherapeutic agents. Emerging data from other
studies have shown limited clinical efficacy of checkpoint inhibitor
monotherapy in ovarian cancer, with response rates ranging from 10-15
Phase 1b Trial and Early Data
The Phase 1b company-sponsored clinical trial is a
single-arm, open-label study of patients who have been diagnosed with
platinum-resistant and sensitive ovarian cancer, and who have completed
first-line treatment with measurable disease. Investigators plan to
enroll up to 40 participants at up to ten sites in the U.S. and Canada.
The study’s primary objective is to assess the safety and immunogenicity
of the treatment, and to determine changes in the immune cell
infiltration into tumors. Secondary objectives include objective
response rate, duration of response, and time to progression.
Investigators are evaluating patients over a 12-month
treatment schedule, collecting biopsy and blood samples before and after
treatment. In addition, investigators are performing CT scans at the
outset for each patient, repeating the scans every two months to
evaluate status of the disease and to assess potential clinical benefit.
In addition to the early findings related to disease
progression and the presence of survivin-antigen specific CD8+ T cells
in the blood, analysis of the tumor revealed increases in multiple T
cell markers, including cytotoxic markers and checkpoint inhibitor
“This readout, while from a limited number of patients, is
important as it marks the first time DPX-Survivac has been tested in
active progressive disease, where we can formally look at its impact on
tumor progression and the tumor microenvironment, as well as assess
potential clinical benefit,” said Marianne Stanford, PhD, Vice President, Research, at Immunovaccine.
“The data set thus far has provided a preliminary indication of
DPX-Survivac’s ability to induce T-cell infiltration in the tumor
micro-environment. We are very encouraged by this information, and we
look forward to the next opportunity to analyze the data and their
related implications for this clinical program.”
Immunovaccine expects to complete enrollment and issue
topline data by the end of 2017. Patients interested in enrolling in
this trial can find more information via clinicaltrials.gov.
This triple combination study is the result of a collaboration
between Immunovaccine and Incyte Corporation to assess the safety and
effectiveness of DPX-Survivac, along with epacadostat, an
investigational oral indoleamine 2,3-dioxygenase 1 (IDO1) enzyme
inhibitor, and low-dose cyclophosphamide in patients with recurrent
ovarian cancer who have measurable disease.
About Ovarian Cancer
According to the American Cancer Society (ACS)iii,
ovarian cancer ranks fifth in cancer deaths among women, accounting for
more deaths than any other cancer of the female reproductive system.
Often diagnosed in its advanced stages, about 21,290 women received a
new diagnosis of ovarian cancer in 2015; approximately 14,180 women
would die from the disease, according to ACS estimates.
Ovarian cancer has a significant impact globally as well. The World Cancer Research Fundiv
reports that ovarian cancer is the seventh most common cancer in women
worldwide (18 most common cancer overall), with 239,000 new cases
diagnosed in 2012.
DPX-Survivac consists of survivin-based peptide antigens
formulated in the DepoVax™ platform, which is a patented formulation
that provides controlled and prolonged exposure of antigens to the
immune system, resulting in a strong, specific and sustained immune
response. The National Cancer Institute (NCI) has recognized survivin as
a promising tumor-associated antigen (TAA) because of its therapeutic
potential and its cancer specificity. Survivin is broadly over-expressed
in multiple cancer types in addition to ovarian cancer, including
breast, colon and lung cancers. Survivin plays an essential role in
antagonizing cell death, supporting tumor-associated angiogenesis, and
promoting resistance to anti-cancer therapies. Survivin is also a
prognostic factor for many cancers and it is found in a higher
percentage of tumors than other TAA’s.
The DPX-Survivac vaccine is thought to work by eliciting a
cytotoxic T-cell immune response against cells presenting survivin
peptides. This targeted therapy attempts to use the immune system to
search actively and specifically for tumor cells and destroy them.
Survivin-specific T-cells have been shown to target and kill
survivin-expressing cancer cells while sparing normal cells.
DPX-Survivac has been granted Fast Track designation by the
U.S. FDA as maintenance therapy in individuals with advanced ovarian,
fallopian tube, and peritoneal cancer who have no measureable disease
following surgery and front-line platinum/taxane chemotherapy to improve
their progression-free survival.
About Epacadostat (INCB24360)
Indoleamine 2,3-dioxygenase 1 (IDO1) is a key
immunosuppressive enzyme that modulates the anti-tumor immune response
by promoting regulatory T-cell generation and blocking effector T-cell
activation, thereby facilitating tumor growth by allowing cancer cells
to avoid immune surveillance. Epacadostat is a first-in-class, highly
potent and selective oral inhibitor of the IDO1 enzyme that reverses
tumor-associated immune suppression and restores effective anti-tumor
immune responses. In single-arm studies, the combination of epacadostat
and immune checkpoint inhibitors has shown proof-of-concept in patients
with unresectable or metastatic melanoma. In these studies, epacadostat
combined with the CTLA-4 inhibitor ipilimumab or the PD-1 inhibitor
pembrolizumab improved response rates compared with studies of the
immune checkpoint inhibitors alone. A Phase 3 study, ECHO-301,
evaluating the combination of epacadostat with the anti-PD-1 antibody
pembrolizumab for the first-line treatment of patients with advanced or
metastatic melanoma is underway. Ongoing Phase 1 and Phase 2 studies are
also investigating epacadostat in combination with PD-1 and PD-L1
inhibitors in a variety of other cancer histologies.
Immunovaccine Inc. is a clinical-stage biopharmaceutical
company dedicated to making immunotherapy more effective, more broadly
applicable, and more widely available to people facing cancer and
infectious diseases. Immunovaccine develops T-cell activating cancer
immunotherapies and infectious disease vaccines based on DepoVax™, the
Corporation’s patented platform that provides controlled and prolonged
exposure of antigens and adjuvant to the immune system. Immunovaccine
has advanced two T-cell activation therapies for cancer through Phase 1
human clinical trials and is currently conducting a Phase 1b study with
Incyte Corporation assessing its lead cancer therapy, DPX-Survivac, as a
combination therapy in ovarian cancer. An investigator-sponsored Phase 2
study will assess the safety and efficacy of DPX-Survivac and low dose
cyclophosphamide combined with an approved anti-PD-1 drug in advanced
ovarian cancer. The Corporation is also exploring additional
applications of DepoVax™, including DPX-RSV, an innovative vaccine
candidate for respiratory syncytial virus (RSV), which has recently
completed a Phase 1 clinical trial. Immunovaccine also has ongoing
clinical projects to assess the potential of DepoVax™ to address malaria
and the Zika virus. Connect at www.imvaccine.com.
Immunovaccine Forward-Looking Statements
This press release contains forward-looking information
under applicable securities law. All information that addresses
activities or developments that we expect to occur in the future is
forward-looking information. Forward-looking statements are based on the
estimates and opinions of management on the date the statements are
made. However, they should not be regarded as a representation that any
of the plans will be achieved. Actual results may differ materially from
those set forth in this press release due to risks affecting the
Corporation, including access to capital, the successful completion of
clinical trials and receipt of all regulatory approvals and the matters
discussed under “Risk Factors and Uncertainties” in Immunovaccine’s
Annual Information Form filed on Sedar. Immunovaccine Inc.
assumes no responsibility to update forward-looking statements in this
press release except as required by law.
A. Ott, F. Stephen Hodi, Howard L. Kaufman, Jon M. Wigginton and Jedd
D. Wolchok. Combination immunotherapy: a road map. Journal for
ImmunoTherapy of Cancer (2017). 5:16 DOI 10.1186/s40425-017-0218-5
SL, Secord AA, Monk B. 2016. The role of immune checkpoint inhibition
in the treatment of ovarian cancer. Gynecologic Oncology Research and
Practice. (3)11. DOI: 10.1186/s40661-016-0033-6
|iii||What Are the Key Statistics about Ovarian Cancer?” Cancer.org. The American Cancer Society, 12 Mar. 2015. Web. Accessed 29 Dec. 2015.|
|iv||“Ovarian Cancer Statistics.” Cancer Facts and Figures – Data on Specific Cancers. World Cancer Research Fund International. Web. Accessed 29 Dec. 2015.|
Sam Brown Inc.
Chief Financial Officer
O: (415) 513-1284
T: (415) 515-4572
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