SAN DIEGO, Oct. 27, 2017 /PRNewswire/ -- Tocagen Inc.
(Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy
company, today reported updated data demonstrating long-term
durable responses, and the conversion of initial partial responses
(PRs) into complete responses (CRs), from a Phase 1 study of
Tocagen's investigational product, Toca 511 & Toca FC, for the
treatment of patients with recurrent high-grade glioma (HGG), a
type of brain tumor. These updated Phase 1 data were selected for
inclusion in the AACR-NCI-EORTC International Conference on
Molecular Targets and Cancer Therapeutics official press program
(abstract A085) and will be presented in a scientific session at
10:50 a.m. ET today by Clark Chen, M.D., Ph.D., Lyle French Chair in
Neurosurgery and head of the University of
Minnesota Medical School Department of Neurosurgery.
![Tocagen Tocagen](https://mma.prnewswire.com/media/591695/Tocagen_Logo.jpg)
HGGs are among the most common and aggressive primary brain
cancers. Approximately 160,000 patients worldwide are expected to
be diagnosed with HGG in 2017. The two most common forms of HGGs
are glioblastoma and anaplastic astrocytoma. With current standard
of care, recurrent HGG patients have a median survival of
approximately seven to nine months.
Tocagen's Phase 1 ascending-dose trial involved 56 patients
across seven clinical sites, who, at the time of surgical
resection, received Toca 511, followed by multiple courses of Toca
FC. Some of the cohorts within the study combined the
investigational therapy with antiangiogenic therapy (bevacizumab)
or chemotherapy (lomustine). Data highlights are below.1
The full presentation can be found on Tocagen's website.
Overall Phase 1 Trial Data Summary:
- Toca 511 & Toca FC continued to demonstrate a favorable
safety profile and were well tolerated by patients.
- Tocagen has previously presented CR and PR data for the six
patients who responded to treatment. The data presented today is
updated to show that two previously announced PRs have converted
into CRs, bringing the total number of CRs to six.
-
- Five CRs followed treatment with Toca 511 & Toca FC, and
one CR followed combination treatment with Toca 511 & Toca FC
and bevacizumab.
- Three of the CRs were glioblastoma IDH1 wildtype, one CR was
anaplastic astrocytoma IDH1 wildtype and two CRs were anaplastic
astrocytoma IDH1 mutant
- Responses were observed across six different clinical
sites.
- All responders are complete responders and remain in response.
Median duration of response had not been reached after a median
follow-up of 35.1 months (range: 9.2 to 44.9 months).
- An association between durable response and overall survival is
suggested as all responders remain alive following study entry
(range: 21.4 to 52.2 months).
Toca 5 Qualifying Patient Subgroup:
- In a subgroup analysis of 23 patients in the Phase 1 trial who
were in the high-dose cohorts and would qualify for Tocagen's
ongoing, Phase 3 Toca 5 trial:
-
- Five of 23 patients had a durable complete response, bringing
the durable response rate (objective responses lasting at least 24
weeks) to 21.7%.2
- Median duration of response had not been reached after a median
follow up of 35.7 months (range: 14.1 to 44.9 months).
- Stable disease (lasting at least 8 weeks) was observed in 5
additional patients, bringing the clinical benefit rate to 43.5%
(10/23 patients).
- Median survival was 14.4 months.
- Landmark overall survival rates at two and three years (OS24,
OS36) was 34.8% and 26.1% respectively.
"Once high-grade glioma recurs, the expected survival is
typically measured in months. At recurrence, physicians and
caregivers are left with limited treatment options," said Dr. Chen.
"Today's results show some high-grade glioma patients are
experiencing complete responses and living multiple years after
receiving Toca 511 & Toca FC. The duration of response and
the number of patients with durable response or stable disease are
impressive in this Phase 1 study, supporting further evaluation of
Toca 511 & Toca FC as a potential treatment for recurrent
high-grade glioma."
Added Asha Das, M.D., senior vice
president and chief medical officer of Tocagen, "Patients and
physicians urgently await new treatments for high-grade glioma, one
of the deadliest cancers. We are encouraged by the maturing durable
response results of our earlier trial, and remain committed to
advancing Toca 511 & Toca FC through the ongoing Phase 3 Toca 5
trial to bring a potentially transformative product to patients as
quickly as possible."
About the Toca 5 Trial
Toca 5 is a Phase 3, pivotal, randomized, double-blind study of
Toca 511 & Toca FC in patients with recurrent high-grade
glioma, a type of brain tumor. The study is being conducted at 167
sites globally and is expected to enroll 380 patients. Patients
will be randomized following surgical resection 1:1 to receive
either the Toca 511 & Toca FC regimen or chemotherapy. The
primary endpoint of the trial is overall survival (OS). The primary
endpoint assumes a median OS of 9.8 months for the control arm
versus 14.3 months for the Toca 511 & Toca FC arm. A total of
257 events will provide the study with 85% power to detect a hazard
ratio of 0.685. Interim analyses are planned at 50% and 75% of
events. More information can be found at www.tocagen.com/toca5 or
by searching clinicaltrials.gov using the clinical trial identifier
NCT02414165.
About Toca 511 & Toca FC
Tocagen's lead product candidate is a cancer-selective
immunotherapy comprised of an investigational biologic, Toca 511,
and an investigational small molecule, Toca FC, that are designed
to be used together. Toca 511 is an injectable retroviral
replicating vector (RRV) that encodes a prodrug activator enzyme,
cytosine deaminase (CD). CD is derived from yeast, and humans do
not naturally have this gene. Its selective delivery to cancer
cells means that the infected cancer cells selectively carry the CD
gene and produce CD. Toca FC is an investigational orally
administered prodrug, 5-fluorocytosine (5-FC) that is inactive as
an anti-cancer drug. In animal models, Tocagen has shown
that 5-FC is converted into the anticancer drug, 5-FU, at high
concentrations in Toca 511-infected cancer cells that are producing
CD. Together, the Toca 511 & Toca FC combination directly kills
cancer cells and immune-suppressive myeloid cells resulting in
activation of the immune system against the cancer.
About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy
company developing first-in-class, broadly applicable product
candidates designed to activate a patient's immune system against
their own cancer. Tocagen is developing its lead investigational
product candidate, Toca 511 & Toca FC, initially for the
treatment of recurrent highgrade glioma (HGG), a disease with
significant unmet medical need. The U.S. Food and Drug
Administration (FDA) has granted Toca 511 & Toca FC
Breakthrough Therapy Designation for the treatment of recurrent HGG
and the European Medicines Agency (EMA) has granted Toca 511 PRIME
(PRIority MEdicines) designation for the treatment of HGG.
Forward-Looking Statements
Statements contained in this press release regarding matters
that are not historical facts are "forward-looking statements"
within the meaning of the Private Securities Litigation Reform Act
of 1995. Because such statements are subject to risks and
uncertainties, actual results may differ materially from those
expressed or implied by such forward-looking statements. Such
statements include, but are not limited to, statements regarding
our business plans and objectives, expectations regarding the
timing and success of our clinical trials and planned clinical
trials. Risks that contribute to the uncertain nature of the
forward-looking statements include: the success, cost and timing of
our product candidate development activities and planned clinical
trials; our ability to execute on our strategy; regulatory
developments in the United States
and foreign countries; and our estimates regarding expenses, future
revenue and capital requirements. These and other risks and
uncertainties are described more fully under the caption "Risk
Factors" and elsewhere in Tocagen's filings and reports with the
United States Securities and Exchange Commission. All
forward-looking statements contained in this press release speak
only as of the date on which they were made. Tocagen undertakes no
obligation to update such statements to reflect events that occur
or circumstances that exist after the date on which they were
made.
1Data cutoff date was Aug.
15, 2017.
2Responses were assessed
using Macdonald Criteria including MRI
assessment by independent radiology review and clinical
data.
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SOURCE Tocagen Inc.