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Clovis Oncology’s CO-1686 Demonstrates Encouraging Results from Ongoing Phase I/II Study in EGFR-mutant Non-Small Cell Lung

  Clovis Oncology’s CO-1686 Demonstrates Encouraging Results from Ongoing
  Phase I/II Study in EGFR-mutant Non-Small Cell Lung Cancer

  *Four RECIST partial responses observed in heavily pretreated T790M+
                                     patients
  *Three of four evaluable T790M+ patients treated at 900 mg BID achieved
                                partial responses
   *CO-1686 appears well-tolerated; no evidence of wild-type EGFR inhibition
                *Activity correlates with higher drug exposure
  *Phase II dose not yet defined; MTD not yet reached

2013 ASCO Annual Meeting

Business Wire

BOULDER, Colo. -- June 3, 2013

Clovis Oncology (NASDAQ:CLVS) today announced initial 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. Initial results from the Phase I
dose-escalation portion of this Phase I/II study are being presented for the
first time on Tuesday, June 4 at a poster session during the American Society
of Clinical Oncology (ASCO) Annual Meeting 2013 in Chicago. Four RECIST
partial responses in T790M positive patients have been observed to date, and
the maximum tolerated dose (MTD) has not yet been reached.

"The oncology community has been working to develop successful treatments for
EGFR mutant patients with acquired resistance to erlotinib or gefitinib for
several years withoutsignificant progress,” said Dr. Lecia V. Sequist of the
Massachusetts General Hospital Cancer Center and AssociateProfessor
ofMedicine atHarvard Medical School,Boston. “It has been exciting and quite
hopeful to observe that patientsare responding to CO-1686andthat the side
effect profile has been so mild. A drug that works effectivelyfor EGFR
acquired resistance would be welcomed by the lung cancer community."

“There are no approved treatment options for patients with non-small cell lung
cancer who have developed the T790M resistance mutation,” said Patrick J.
Mahaffy, President and CEO of Clovis Oncology. “We are extremely encouraged by
these initial results which suggest that CO-1686 is well-tolerated and offers
clear evidence of meaningful activity in a heavily pre-treated patient
population, despite not yet having established our MTD. We look forward to
continuing dose-escalation with our improved tablet formulation in our Phase
I/II trial, with the goal of identifying the dose to proceed into the
expansion cohorts in our target patient populations and our registration
studies.”

The Phase I dose escalation portion of the study is being conducted in the
United States and France 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). Study objectives were typical for a Phase I
trial: determining safety and tolerability, evaluating the pharmacokinetic
profile, maximum tolerated dose (MTD) and recommended Phase II dose (RP2D), as
well as identification of preliminary efficacy signals.

Forty-two patients have been treated with CO-1686 as of May 2013, mostly in
once-daily (QD) and twice-daily (BID) dosing cohorts up to 900mg QD and 900mg
BID. Dose-escalation will continue with an improved formulation in the third
quarter as the MTD has not yet been reached.

Key data from the study presented at ASCO include:

Evidence of Activity

Objective responses have been observed in heavily pretreated T790M+ patients
who are resistant to erlotinib. Additionally, metastasis shrinkage has been
observed at multiple organ sites, including both brain and liver metastases.

Included in the poster are six T790M+ patients, including four with RECIST
(v1.1) partial responses (PRs) and two patients with tumor shrinkage of
greater than 20 percent. Details on each patient follow:

  *One patient with a del19/T790M+ tumor had progressed on erlotinib
    immediately before beginning CO-1686 therapy. The patient, enrolled in the
    300 mg BID cohort, is currently in cycle 6 of CO-1686 therapy, with a
    confirmed PR
  *One patient with an L858R/T790M+ tumor had received six previous lines of
    therapy, including two previous TKIs, dacomitinib and erlotinib, and had
    most recently progressed on a combination of erlotinib and gemcitibine
    immediately before beginning CO-1686 therapy. This patient has
    demonstrated tumor shrinkage in brain metastases (present at baseline), as
    well as lung and liver tumors. The patient, enrolled in the 900mg BID
    cohort, exhibited a PR in cycle 4 of CO-1686 therapy; treatment is ongoing
  *One patient with a del19/T790M+ tumor had received two previous lines of
    therapy. This patient exhibited a PR in cycle 2 and is currently being
    dosed in cycle 3 at 900mg BID
  *One patient with a del19/T790M+ tumor had received two lines of prior
    cytotoxic chemotherapy and had also progressed on erlotinib treatment.
    This patient exhibited a PR in cycle 2 and is currently in cycle 3,
    receiving 900mg BID
  *Two additional T790M+ patients have achieved greater than 20 percent
    target lesion shrinkage with stable non-target lesions

A total of six patients have been treated in the 900mg BID cohort (the highest
dose evaluated to date): one of these patients is not evaluable for response
and one patient is T790M-negative. Three of the four remaining patients
achieved PRs, as described above, and the fourth has stable disease at the end
of cycle 2.

Safety and Tolerability

CO-1686 appears to be well-tolerated with no evidence of dose-related diarrhea
or rash. There were 26 patients (62%) with treatment-related adverse events.
The most common adverse events attributed to CO-1686 therapy include fatigue
(19%), nausea (17%), diarrhea (14%), muscle spasms (10%), and anemia (10%).
These were all grade 1/2 in severity and did not lead to study drug
discontinuation. There have been two dose limiting toxicities (DLTs):

  *One event of hypoglycemia in the 150 mg QD cohort in a diabetic patient
    who took oral hypoglycemic agents while fasting
  *One acute illness in the 900 mg BID cohort on day three of dosing with
    anorexia and asthenia (grade 3), abnormal liver function tests (grade 3)
    and diarrhea (grade 2)

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.

Pharmacokinetics

The activity and safety data presented at ASCO, using the free base capsule
formulation, demonstrated that plasma exposure of CO-1686 increases with dose
and activity appears to correlate to drug exposure. Non-clinical data
suggested that maintenance of trough concentrations over 200ng/mL for >12-18
hours was associated with optimal efficacy. In the Phase I portion of the
Phase I/II study, T790M+ patients for whom Cmin levels of 200 ng/mL or greater
were maintained for 16 hours or more demonstrated improved progression-free
survival (PFS) compared to those with inferior exposures. Objective responses
were observed exclusively in the higher-exposure group as well:

  *For T790M+ patients with Cmin greater than 200 ng/mL for 16 hours or
    longer, median PFS was 194 days; 50 percent had a 10% or greater tumor
    shrinkage;
  *For T790M+ patients with Cmin greater than 200 ng/mL for fewer than 16
    hours, median PFS was 72.5 days; 8 percent of patients had a 10 percent or
    greater shrinkage

The ASCO poster also presented data with the hydrobromide salt tablet form of
CO-1686 from a separate Phase I study in healthy human volunteers, which
showed improved exposure and reduced PK variability compared with the current
free base capsule formulation, which is being used in the Phase I study in
patients with NSCLC. Specifically, in the ongoing Phase I study in healthy
volunteers, the tablet form of CO-1686 demonstrated a 2 to 3-fold improvement
in absorption and a 4-fold reduction in exposure variability relative to the
free base capsule formulation.

As previously stated, the Company intends to transition development of
CO-1686, including dose escalation in the ongoing Phase I study, to the tablet
formulation in the third quarter of 2013. The Company plans to use the tablet
formulation in all future clinical studies of CO-1686.

Poster Presentation

The poster, titled “First-in-human evaluation of CO-1686, an Irreversible,
Selective, and Potent Tyrosine Kinase Inhibitor of EGFR T790M”, is being
presented on Tuesday, June 4, 8:00 a.m.-12:00 p.m. CDT, in Room E450a at
McCormick Place in Chicago. The poster will also be available at
www.clovisoncology.com.

The poster will be discussed at the associated discussion session with Dr.
David Carbone of Ohio State’s Comprehensive Cancer Center – James Cancer
Hospital and Solove Research Institute serving as discussant. The discussion
session will be held on Tuesday, June 4, 11:30 a.m.-12:30 p.m. CDT, with Dr.
Carbone scheduled to speak from 11:54 a.m.–12:06 p.m. in Room E354b.

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. and
France. Following the establishment of an appropriate dose, the Company
intends to study CO-1686 in a Phase II expansion cohort of NSCLC patients with
activating EGFR mutations who have failed initial EGFR-directed therapy and
have developed the T790M mutation, as well as a second expansion cohort of
first-line mutant EGFR NSCLC patients.

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 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 our drug candidates. Clovis Oncology undertakes no obligation 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
Anna Sussman, 303.625.5022
asussman@clovisoncology.com
or
Breanna Burkart, 303.625.5023
bburkart@clovisoncology.com
 
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