Clovis Oncology’s CO-1686 Continues to Demonstrate Promising Clinical Activity and Safety in Updated Phase I Study Results

  Clovis Oncology’s CO-1686 Continues to Demonstrate Promising Clinical
  Activity and Safety in Updated Phase I Study Results

  *67 percent objective response rate in heavily pretreated T790M+ patients
    dosed at 900mg BID of free base formulation
  *New hydrobromide (HBr) formulation shows significantly improved exposures
    and reduced variability compared with free base in first cohort treated
  *No rash or diarrhea of any grade, or dose-limiting toxicities seen at
    500mg BID dose of HBr formulation, despite substantial exposures

Business Wire

SYDNEY -- October 27, 2013

Clovis Oncology (NASDAQ:CLVS) announced today updated findings from the Phase
I portion of its ongoing Phase I/II clinical study of CO-1686, the Company’s
novel, oral, targeted covalent (irreversible) inhibitor of mutant forms of the
epidermal growth factor receptor (EGFR) for the treatment of non-small cell
lung cancer (NSCLC) in patients with initial activating EGFR mutations as well
as the dominant resistance mutation T790M. Interim results from the Phase I
dose-escalation portion of this Phase I/II study are being presented today in
an oral presentation by Professor Jean-Charles Soria at the IASLC 15^th World
Conference on Lung Cancer in Sydney.

Six RECIST partial responses have been observed to date in nine evaluable
T790M positive patients dosed at 900mg BID of the free base formulation, for a
67 percent objective response rate. Eight of the nine evaluable patients, or
89 percent, experienced tumor shrinkage greater than 10 percent. Fifty-six
patients have been treated with CO-1686 to date across all dosing cohorts,
with no evidence of systemic wild-type EGFR-driven toxicities such as rash.
Dose escalation is ongoing with the improved HBr formulation, currently dosing
at 750mg BID, as the maximum tolerated dose (MTD) has not yet been reached.

“These results are exciting, and confirm and extend the initial data reported
at ASCO 2013 for this new agent,” said Professor Jean-Charles Soria, Professor
of Medicine and Medical Oncology at Paris University XI and cancer specialist
at Gustave Roussy Institute. “The T790M acquired resistance mutation is a
critical problem in mutant-EGFR lung cancer patients, and CO-1686 appears to
be meaningfully benefiting these patients, without triggering the skin and GI
toxicities typically seen with older EGFR inhibitors that are not
mutant-selective.”

“CO-1686 continues to demonstrate impressive activity and is very well
tolerated in these heavily pre-treated patients,” said Patrick J. Mahaffy,
president and CEO of Clovis Oncology. “Additionally, the initial
pharmacokinetic and safety data from patients in the ongoing Phase I
dose-finding study with the hydrobromide formulation are very promising. We
are very optimistic about this new formulation since we are already seeing
such encouraging results with an inferior formulation at a suboptimal dose. We
look forward to identifying the recommended Phase II dose for CO-1686 and
quickly proceeding into our first registration study.”

The Phase I dose escalation portion of the study is being conducted in the
United States, France and Australia in patients with metastatic or
unresectable recurrent NSCLC and a documented EGFR mutation. Patients were not
required to be T790M positive for the Phase I portion of the study but had to
have progressed on prior EGFR-directed tyrosine kinase inhibitor (TKI) therapy
(prior chemotherapy was also allowed).

Evidence of Activity

As of October 2013, nineteen patients have been treated in the 900mg BID
cohort. Of those nineteen patients, five were T790M negative and fourteen were
T790M positive (five non-evaluable).

In the nine evaluable T790M positive patients, a 67 percent overall response
rate was demonstrated. Six patients achieved RECIST partial responses and two
patients achieved tumor shrinkage of 10-20 percent. Patients were heavily
pretreated prior to receiving CO-1686; eight of the nine patients had
immediately progressed on a TKI prior to treatment. Six of the nine patients
received two or more previous TKI lines. As expected, no objective responses
were seen in T790M negative patients.

Previously, the Company reported data at ASCO for a total of four evaluable
T790M positive patients treated in the 900mg BID cohort; one patient with
stable disease and three patients with PRs. Additionally, the Company reported
one patient with a PR from the 300mg BID cohort. Of the four patients with
PRs, three of the four remain on drug. Two patients have maintained their
responses and one patient remains on drug despite having formally progressed.
The median progression free survival time for these four responding patients
has not yet been reached but is greater than 181 days.

Safety and Tolerability

CO-1686 appears to be well-tolerated with no evidence of rash or dose-related
diarrhea. There are limited and low-grade adverse events in patients to date.
The most common adverse events attributed to CO-1686 therapy include nausea
(21%), diarrhea (20%), fatigue (20%), vomiting (13%) and decreased appetite
(11%). These did not lead to study drug discontinuation.

The incidence of adverse events did not increase with dose escalation and does
not appear to be dose dependent. These data offer no evidence of dose-related
adverse events related to wild-type EGFR inhibition by CO-1686.

Hydrobromide Formulation

In August, the Company transitioned development of CO-1686 from an initial
free base capsule presentation to a tablet HBr formulation. Preliminary
pharmacokinetic data from the first cohort of three patients treated at 500mg
BID are being presented today. The HBr formulation at the 500mg BID dose was
expected to demonstrate approximately equivalent exposures with reduced
variability compared with the free base formulation at the 900mg BID dose.
Data from the first cohort of the HBr formulation has demonstrated far greater
exposures than expected, with no adverse events. There has been no evidence of
cutaneous or gastrointestinal toxicity of any grade in the 500mg BID cohort,
and no dose limiting toxicity, and enrollment of the 750mg BID cohort has
commenced.

Presentation Details

The presentation, titled “First-in-human evaluation of CO-1686, an
Irreversible, Selective, and Potent Tyrosine Kinase Inhibitor of EGFR T790M
(Activating and T790M),” is being presented on Monday, October 28, between
10:30am-12 noon in the Bayside B Auditorium at the Sydney Convention and
Exhibition Centre. The presentation will also be available at
www.clovisoncology.com.

About CO-1686

CO-1686 is a novel, oral, targeted covalent (irreversible) inhibitor of the
cancer-causing mutant forms of epidermal growth factor receptor (EGFR)
currently being studied for the treatment of non-small cell lung cancer
(NSCLC). CO-1686 was designed to selectively target both the initial
activating EGFR mutations as well as the T790M resistance mutation, while
sparing wild-type, or “normal” EGFR at anticipated therapeutic doses.
Accordingly, it has the potential to treat NSCLC patients with EGFR mutations
both as a first-line or second-line treatment with a reduced toxicity profile
compared to current EGFR inhibitor therapies. The Phase I/II study is
currently in the dose escalation phase, being conducted in the U.S., France
and Australia. Following the establishment of an appropriate dose, the Company
intends to study CO-1686 in Phase II expansion cohorts of NSCLC patients with
activating EGFR mutations who have failed initial EGFR-directed therapy and
have developed the T790M resistance mutation as well as NSCLC treatment-naïve
patients with activating EGFR mutations.

About Clovis Oncology

Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring,
developing and commercializing innovative anti-cancer agents in the U.S.,
Europe and additional international markets. Clovis Oncology targets
development programs at specific subsets of cancer populations, and
simultaneously develops diagnostic tools that direct a compound in development
to the population that is most likely to benefit from its use. Clovis Oncology
is headquartered in Boulder, Colorado, and has additional offices in San
Francisco, California and Cambridge, UK.

To the extent that statements contained in this press release are not
descriptions of historical facts regarding Clovis Oncology, they are
forward-looking statements reflecting the current beliefs and expectations of
management made pursuant to the safe harbor provisions of the Private
Securities Litigation Reform Act of 1995. Such forward-looking statements
involve substantial risks and uncertainties that could cause our clinical
development programs, future results, performance or achievements to differ
significantly from those expressed or implied by the forward-looking
statements. Such risks and uncertainties include, among others, the
uncertainties inherent in our clinical development program for CO-1686,
including the uncertainties inherent in the initiation of future clinical
trials, availability of data from ongoing clinical trials, expectations for
regulatory approvals, and other matters that could affect the availability or
commercial potential of the drug product candidate. Clovis Oncology does not
undertake to update or revise any forward-looking statements. For a further
description of the risks and uncertainties that could cause actual results to
differ from those expressed in these forward-looking statements, as well as
risks relating to the business of the company in general, see Clovis
Oncology’s Annual Report on Form 10-K for the year ended December31, 2012 and
its other reports filed with the Securities and Exchange Commission.

Contact:

Clovis Oncology, Inc.
Anna Sussman, 303.625.5022
asussman@clovisoncology.com
or
Breanna Burkart, 303.625.5023
bburkart@clovisoncology.com
 
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