-
67 percent objective response rate in heavily pretreated T790M+
patients dosed at 900mg BID of free base formulation
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New hydrobromide (HBr) formulation shows significantly improved
exposures and reduced variability compared with free base in first
cohort treated
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No rash or diarrhea of any grade, or dose-limiting toxicities seen
at 500mg BID dose of HBr formulation, despite substantial exposures
SYDNEY--(BUSINESS WIRE)--Oct. 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 15thWorld
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 December 31, 2012 and its other reports filed with the Securities
and Exchange Commission.
Source: Clovis Oncology, Inc.
Clovis Oncology, Inc.
Anna Sussman, 303.625.5022
asussman@clovisoncology.com
or
Breanna
Burkart, 303.625.5023
bburkart@clovisoncology.com