SAN DIEGO, Oct. 26, 2017 /PRNewswire/ -- Tocagen Inc.
(Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy
company, today announced the company has updated the protocol of
the ongoing Toca 5 clinical trial of Toca 511 & Toca FC for the
treatment of patients with recurrent high-grade glioma (HGG), a
type of brain tumor.
Based on Tocagen's communications with the U.S. Food and Drug
Administration (FDA) under Breakthrough Therapy Designation,
Tocagen will immediately accelerate Toca 511 & Toca FC clinical
development by modifying the original two-step trial design (Phase
2 followed by a Phase 3) into a seamless, pivotal trial, known as
the Toca 5 trial.
"We are pleased with the outcome of our discussions with FDA
under Breakthrough Therapy Designation, resulting in a pivotal
Phase 3 trial," said Marty Duvall,
chief executive officer of Tocagen. "This advance allows us to
expedite development of Toca 511 & Toca FC in support of our
mission to bring clinicians and patients a new treatment option for
this aggressive form of brain cancer."
Highlights of the revised trial design are as follows:
- An additional 193 patients with recurrent HGG will be enrolled
and pooled with 187 already enrolled patients, for a total target
enrollment of 380 patients.
- 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.
- Secondary endpoints of the trial include durable response rate,
defined as complete or partial responses lasting at least 24 weeks,
which is being assessed as a novel endpoint in the post-surgical
setting of recurrent HGG.
- The updated protocol includes planned interim analyses at 50%
and 75% of events, estimated to occur in the second half of 2018
and first half of 2019, respectively. Due to this transition to a
seamless trial design, a previously planned data analysis of the
Phase 2 portion of the original Phase 2/3 trial will no longer
occur.
- Additionally, the FDA awarded Tocagen a $2 million orphan drug grant, payable over four
years, to support the Toca 5 trial. More details on the grant are
available at FDA.gov.
"The maturing data from our Phase 1 resection trial in patients
with recurrent brain cancer gives us confidence to move forward
with a seamless pivotal trial rather than waiting to initiate a
separate Phase 3 study," said Asha
Das, M.D., senior vice president and chief medical officer
of Tocagen. "We will be sharing these updated data in an oral
presentation at the AACR-NCI-EORTC meeting tomorrow."
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 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 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 high grade 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 of our clinical trials, including the timing of enrollment,
interim analyses and results from our 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.
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SOURCE Tocagen Inc.