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Objective responses seen in BRCA-mutant ovarian, breast and
pancreatic cancer patients
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89% clinical benefit rate in ovarian cancer patients across all
doses
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Rucaparib well-tolerated at doses studied
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Consistent therapeutic drug exposures observed with BID dosing
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Phase II dose not yet defined; MTD not yet reached
BOULDER, Colo.--(BUSINESS WIRE)--Jun. 3, 2013--
Clovis Oncology (NASDAQ:CLVS) today announced initial findings from an
ongoing Phase I/II monotherapy study of rucaparib, the Company’s oral,
potent, small molecule poly (ADP-ribose) polymerase (PARP) inhibitor
being developed for the treatment of ovarian cancer. Initial results
from the Phase I dose-escalation portion of this Phase I/II study are
being presented for the first time today at a poster session during the
American Society of Clinical Oncology (ASCO) Annual Meeting 2013 in
Chicago.
“Oral rucaparib is a potent PARP inhibitor active in patients with
ovarian, breast and pancreatic cancers. Clinically meaningful results
have been seen in the rucaparib monotherapy Phase I trial; 89% of
patients with ovarian cancer demonstrated a clinical benefit. Increasing
evidence suggests that genetic analysis of ovarian tumors can help
identify patients who derive benefit from PARP inhibitor therapy – best
known predictors are mutations in BRCA genes, either at germline or
somatic level, but there are likely other predictive mutations as well.
The Clovis development program seeks to exploit these new insights and I
am pleased to be jointly leading their larger-scale trials to assess the
full clinical potential of this well-tolerated drug in ovarian cancer,”
said Professor Jonathan Ledermann, Professor of Medical Oncology &
Director, Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer
Institute.
“These initial results suggest that rucaparib is both well-tolerated and
predictably absorbed, and provides meaningful clinical benefit to
certain ovarian cancer patients,” said Patrick J. Mahaffy, President and
CEO of Clovis Oncology. “Once we identify the recommended Phase II dose,
we look forward to commencing the late-stage development program in
platinum-sensitive ovarian cancer in 2H13. This comprises two trials - a
biomarker study which will refine the definition of patients beyond
those with mutant BRCA who may benefit from rucaparib, and a Phase III
pivotal trial in all patients with a stratified efficacy analysis in
genetically-defined groups, including somatic and germline BRCA
mutations as well as a broader population with mutations beyond BRCA,
utilizing insights from the biomarker study.”
The Phase I dose escalation portion of the study is open to patients
with all solid tumors. Study objectives were typical for a Phase I
trial, including determining safety and tolerability, evaluating the
pharmacokinetic profile, identifying the maximum tolerated dose (MTD)
and recommended Phase II dose (RP2D) as well as the preliminary efficacy
signals in various solid tumors.
Thirty-seven patients have been treated with rucaparib monotherapy in
this study as of May 2013, in once-daily (QD) and twice-daily (BID)
dosing cohorts, up to 300 mg QD and 480 mg BID. Dose-escalation
continues and the MTD has not yet been reached.
Patients have received a median of four previous anticancer regimens and
over half have received three or more previous therapies. Twenty-one
patients (57%) have breast tumors, 10 patients (27%) have
ovarian/peritoneal tumors and six patients (16%) have other solid tumors.
Key data from the study presented at ASCO include:
Evidence of Activity
Objective responses have been observed in ovarian, breast and pancreatic
cancer patients with germline BRCA mutations. Durable disease control
has been observed in heavily pre-treated ovarian cancer patients across
all dose levels, with a disease control rate of 89% (stable disease or
better beyond 12 weeks after study initiation in 8 of 9 ovarian cancer
patients). The disease control rate for germline BRCA mutant ovarian
cancer patients was 100% (7 of 7). Measurable disease was not a
requirement for entry into the dose escalation phase of the study,
precluding systematic response analysis.
Safety and Tolerability
Safety data to date shows rucaparib to be well-tolerated, which is
important for a drug intended to be used in a maintenance setting. There
were 19 patients (54%) with treatment-related adverse events. The most
common adverse events attributed to rucaparib therapy include fatigue
(23%), nausea (14%) and decreased appetite (11%). No patient experienced
a treatment-related adverse event that led to study drug discontinuation
and no grade 3/4 myelosuppression has been observed in any patient.
There have been two treatment related grade 3 toxicities: one patient
with grade 3 nausea and one patient with grade 3 fatigue.
Pharmacokinetics
Oral rucaparib has attractive pharmacokinetic properties as a potential
oral cancer therapeutic. Patients receiving BID doses above 240 mg
experienced consistently high plasma drug concentrations throughout the
24-hour period, which is likely important for optimal activity. Intra-
and inter-patient variability was also low, which is advantageous for
uniform flat dosing strategies.
The poster, titled “A Phase I Dose Escalation and Pharmacokinetic Study
of Continuous Oral Rucaparib in Patients with Advanced Solid Tumors,” is
being presented on Monday, June 3, 8:00am – 11:45am CDT, in S Hall A2,
Poster Board: 7E at McCormick Place in Chicago. The poster will also be
available at www.clovisoncology.com.
About Rucaparib
Rucaparib is an oral, potent inhibitor of PARP1 and PARP2 in development
for the treatment of ovarian cancer. Rucaparib is currently in two
Company-sponsored Phase I clinical studies; one to determine the maximum
tolerated dose (MTD) of oral rucaparib administered on a daily basis as
monotherapy; and a second trial to determine the MTD of oral rucaparib
that can be combined with intravenous platinum chemotherapy for the
treatment of solid tumors. Once the optimal dose and schedule have been
established in the Phase I portion of the monotherapy study, the Company
will initiate a Phase II expansion cohort to assess efficacy in selected
ovarian cancer patients. The Company expects to initiate a biomarker
study in platinum-sensitive ovarian cancer patients in the third quarter
of 2013, as well as the pivotal Phase III study in platinum-sensitive
ovarian cancer patients in late 2013.
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 December 31,
2012 and its other reports filed with the Securities and Exchange
Commission.
Source: Clovis Oncology
Clovis Oncology
Anna Sussman, 303-625-5022
asussman@clovisoncology.com
or
Breanna
Burkart, 303-625-5023
bburkart@clovisoncology.com