Download Healthy volunteer studies for oncology drug development

Quotient-Gillian-2_Layout 1 28/10/2014 11:48 Page 1
Healthy volunteer studies for
oncology drug development
Clovis Oncology has chosen Quotient Clinical’s RapidFACT™ approach
for rociletinib, a promising oral candidate drug for the treatment of
EGFR-resistant non-small cell lung cancer. Performed on healthy
volunteers, this flexible, data-driven Phase I development study
enabled rapid development of an optimized salt formulation.
Gillian C. Ivers-Read, Executive Vice President, Technical Operations
and Chief Regulatory Officer and one of the co-founders of Clovis
Oncology, described how working with Quotient Clinical led to the
quick and efficient completion of the study.
“Quotient is…
an honest and
straightforward
company with
a very
progressive
attitude.”
Gillian C. Ivers-Read
Clovis Oncology is a US-based
biopharmaceutical company that
focuses on acquiring, developing
and commercializing cancer
treatments for global markets.
The company’s current
development programs are
targeted at specific subsets of
cancer, and combine personalized
medicine with companion
diagnostics, aiming to create
therapeutics that are directed at
the patients most likely to benefit
from them. Gillian explained:
“Our overlying philosophy is to
develop drugs that will be important
for patients. In order to achieve this,
the company ethos is to evaluate
information, both positive and
negative, and make decisions in a
fast and proactive way, to keep
projects moving ahead.”
A significant unmet
clinical need
Non-small cell lung cancer
Clovis owns global development
and commercialization rights to
rociletinib, one of three product
candidates in clinical development,
which is currently in Phase II
development for the treatment of
non-small cell lung cancer. At
present, when patients are
diagnosed with lung cancer, they
are tested to see whether they
have certain epidermal growth
factor receptor (EGFR) mutations
on the cell surface and, if positive,
are treated with tyrosine kinase
inhibitors such as Tarceva® or
Iressa®. Initially, patients respond
very well to these drugs but, after
about a year, they tend to develop
resistance and relapse. More than
50 percent of this drug resistance
is driven by the T790M
‘gatekeeper’ mutation, and
rociletinib is the first drug to be
identified that specifically targets
this mutation.
In epidemiological terms, about
15 percent of all lung cancers in
Europe and the US are EGFR
positive, and about 60 percent of
these develop the T790M
resistance mutation. However,
these figures are doubled in Asian
populations, and the biggest
demographic to be affected is
comparatively young, nonsmoking Asian women. As such,
rociletinib is a key potential
therapy for a significant unmet
clinical need, and an important
candidate to push forward
through an accelerated clinical
development program.
Choosing a study partner
Drug development is complicated
and challenging, and a culture of
thorough, open communication
between both internal teams and
external partners is essential.
Quotient-Gillian-2_Layout 1 28/10/2014 11:48 Page 2
About RapidFACTTM
RapidFACT – Rapid Formulation development And Clinical Testing
RapidFACT dramatically speeds up the optimization of drug products for downstream
development for all routes of delivery. Quotient Clinical’s team of experts assess candidate
molecules and share ideas on the design of development programs. RapidFACT programs
have been successfully used for:
• evaluating solubilization technologies;
• optimizing modified release systems;
• changing route of delivery;
• and developing combination products.
Gillian added: “Contract partners
must be able to form a good
interactive project team, and must
deliver timely, quality work. From the
outset, we were impressed with
Quotient Clinical; as a company, it
appears to have a similar business
culture to our own, particularly in
terms of flexibility and fast working,
and we began to discuss options for
studying rociletinib in healthy
volunteers.”
It is frequently inappropriate to
perform oncology drug studies on
healthy volunteers, purely because
of their significant safety profiles;
however, rociletinib is a targeted
therapy and therefore does not
have the adverse event profile of
some chemotherapeutic agents.
Gillian continued: “In discussion
with Quotient’s medical team, we
established that performing the
studies in healthy volunteers was a
safe option and would make it
considerably faster to transition
patients to what could be a
therapeutic dose. Usually in
oncology, studies like this must work
up doses gradually, but what tends
to happen is that the first few doses
are really sub-therapeutic. This
would therefore be a great
advantage to get to the right level
to see some efficacy as soon as
possible.”
The healthy volunteer study,
designed in association with
Quotient and based on its
proprietary RapidFACT program,
looked at different formulations to
take forward to a clinical study
and, in particular, at moving from
a free base to a salt formulation.
The aim was to quickly transition
patients to this new formulation,
establishing doses of the salt
which would give similar plasma
levels to the doses already
showing efficacy in the free
base form.
“Typically in these kinds of trials, the
drug is made at a manufacturing
unit, and then released, packaged
and shipped to wherever the study is
being held. What makes Quotient
unique is the way in which the
pharmaceutical products are made
on site and transferred, without
leaving the building, to the clinical
unit and a good, large and reliable
pool of healthy volunteers. That is
where so much time is saved. We
have never found a group in the US
that does this, and this workflow
instantly cuts two to three months
out of the study timeline.”
“We had a tight timetable but the
company’s capacity to dose the
healthy volunteers, get the
pharmacokinetic data back and be
ready to call us with results, all in a
matter of days, made a huge
difference. We could then work with
the information they had provided
and decide quickly on the next step,
the next dose. This way of working is
very flexible, and enabled us to make
the necessary decisions in a timely
way, moving the drug forward as
efficiently and safely as possible.”
A positive experience
Gillian concluded: “From the outset,
it was apparent that Quotient had
the same kind of philosophy as
Clovis; an honest and straightforward
company with a very progressive
attitude. Once the team had
understood the scope of the project
and given us a timeline, they
absolutely stuck to that. Everything
went efficiently, there were no
surprises. And, when we needed to
add additional scope, additional
arms onto the project, they were very
flexible. This made it easy for us, and
they responded to the urgency that
we felt in getting things started.
Having the vision to develop the
‘single site’ way of working is truly
innovative, and offers a company
like Clovis a really efficient option.
The entire study was a very positive
experience.”
Quotient Clinical
+44 (0) 115 974 9000 or
+1-800-769-3518 (USA)
[email protected]
www.quotientclinical.com
John McDermott, Director,
Drug Product Optimization
[email protected]
www.quotientclinical.com