- Data from ARIEL2 in platinum-sensitive
BRCA-mutant patients demonstrated an overall response rate (ORR) of
82%, a disease control rate (DCR) of 94% and a median
progression-free survival (PFS) of 9.4 months
- Complete responses (CRs) observed in
10% of patients
- Data from ARIEL2 in patients with
BRCA-like signature demonstrated ORR of 45% and DCR of 73% in and a
median PFS of 7.1 months
- In ARIEL2, approximately 60% of
patients treated to date exhibit BRCA-mutant status or BRCA-like
DNA signature
- Data from Study 10, a Phase 2 study of
heavily pretreated germline BRCA-mutant ovarian cancer patients,
demonstrated an ORR of 74%
- 77% ORR observed in patients treated
with at least three prior lines of chemotherapy; median duration of
response in these patients is currently greater than 11 months
- 74% ORR, median duration of response
greater than 11 months observed in 23 BRCA-mutant patients treated
with at least three prior lines of chemotherapy from ARIEL2 and
Study 10 combined
- CRs observed in 13% of patients in this
group
- Enrollment in ARIEL2 Part 2 single-arm
study in heavily pre-treated patients (≥3 prior lines of
chemotherapy) continues with planned NDA submission in 2016
- Data presented at ASCO demonstrate that
rucaparib is well-tolerated with a manageable safety profile. The
most common grade 3/4 treatment-related adverse events (AEs) were
anemia/decreased hemoglobin, fatigue, nausea and transient ALT/AST
elevations
- Only PARP inhibitor to be granted
Breakthrough Therapy designation by the FDA
Clovis Oncology (NASDAQ:CLVS) today announced updated Phase 2
results from two ongoing clinical studies with rucaparib: ARIEL2
and Study 10. Rucaparib is the Company’s investigational oral,
potent, small molecule inhibitor of PARP1 and PARP2 being developed
for the treatment of advanced ovarian cancer, specifically in
patients with BRCA mutations and other DNA repair deficiencies
beyond BRCA, commonly referred to as “BRCA-like.” Updated data from
the ARIEL2 study in 204 patients with advanced ovarian cancer are
being presented Monday in an oral presentation by Professor Iain
McNeish at the 2015 American Society of Clinical Oncology (ASCO)
annual meeting in Chicago. Additional data from Study 10, a Phase 2
study of 40 platinum sensitive ovarian cancer patients with
germline BRCA mutations were also presented in a poster session
today.
“To see the encouraging progression-free survival rates mirror
the impressive response rates in both the BRCA-mutant and BRCA-like
populations represents a very exciting step forward in the
treatment of advanced ovarian cancer,” said Robert L. Coleman, MD,
Professor & Deputy Chairman, Vice Chair, Clinical Research, Ann
Rife Cox Chair in Gynecology, Department of Gynecologic Oncology
and Reproductive Medicine at University of Texas MD Anderson Cancer
Center in Houston and one of the two principal investigators of the
ARIEL3 study. “The opportunity to provide a very compelling
targeted therapy in an ovarian cancer population in addition to
those who carry germline or somatic BRCA mutation represents a
potentially practice changing advance in the treatment of this
terrible disease.”
“With these data presented at ASCO, we believe rucaparib has
clearly emerged as a unique and best-in-class PARP inhibitor," said
Patrick J. Mahaffy, President and CEO of Clovis Oncology. "In
addition, with our now clinically proven BRCA-like clinical assay,
we have validated our commitment to develop rucaparib not only for
the 25 percent of women with germline and somatic BRCA mutations,
but for the additional approximately 35 percent of women with the
prospectively identified BRCA-like signature. With the ARIEL2
extension enrolling rapidly, we look forward to submitting our NDA
for rucaparib for the treatment of advanced ovarian cancer next
year."
Study objectives of the ARIEL2 trial include determining
rucaparib activity in prospectively defined molecular subgroups
through the assessment of PFS in patients with tumors that have
germline and somatic BRCA mutations, those with a BRCA-like
signature (patients whose tumors have DNA repair deficiencies that
behave like BRCA mutations, but with normal BRCA genes), and
patients whose tumors are biomarker negative. ORR, safety and
pharmacokinetics are also analyzed. At the time of analysis,
patients in the study had received a median of one prior treatment
regimen and one prior platinum-based therapy regimen. Patients were
treated with the recommended Phase 2 dose (RP2D) of 600mg twice
daily (BID).
Updated Results of ARIEL2
Data from the ARIEL2 study of 204 patients show compelling
clinical activity, including the first presentation of PFS for each
subgroup followed in the study. A median PFS of 9.4 months in
BRCA-mutant patients and a median of 7.1 months in patients with a
BRCA-like signature were observed, compared to biomarker negative
patients, in which median PFS was 3.7 months.
The most robust clinical responses were observed in patients
with tumor BRCA mutations: 82 percent (32/39) of BRCA-mutant
patients achieved a RECIST and/or CA-125 response and 69 percent
(27/39) achieved a RECIST response. Responses were observed in both
germline and somatic BRCA-mutant tumors. Four CRs were observed in
the somatic BRCA-mutant group. A 94 percent DCR (CR, PR or SD >
24 weeks) was also observed. Responses were durable with 18 of 27
responders still ongoing at time of analysis. These patients had
received a median of two prior therapies with a range of one to
five prior therapies.
Importantly, results from ARIEL2 demonstrate that tumor HRD
analysis can identify a broader range of patients who may benefit
from rucaparib therapy. Forty-five percent (33/74) of patients with
the pre-specified BRCA-like signature achieved a RECIST and/or
CA-125 response, and 30 percent (22/74) achieved a RECIST response.
Responses were durable with 17 of 22 responders still ongoing at
time of analysis. A 73 percent DCR was also observed.
As expected, activity was limited in biomarker negative
patients, 21 percent (13/62) of patients achieved a RECIST and/or
CA-125 response and 13 percent (8/62) achieved a RECIST response. A
39 percent DCR was also observed.
Data presented demonstrate that rucaparib is well tolerated with
a manageable safety profile. The most common treatment-related AEs
reported in ≥15 percent of all patients included nausea,
asthenia/fatigue and transient ALT/AST elevations. These events
were mostly Grade 1/2. The most common Grade 3/4 treatment-related
AEs were anemia/decreased hemoglobin (16%) and transient ALT/AST
elevations (11%).
Study 10 Data in Platinum-Sensitive Germline BRCA-mutant
Patients
Data from a second Phase 2 study of rucaparib in ovarian cancer
were presented today in a poster presentation and poster discussion
session.
The Phase 2 portion of Study 10, the initial dose finding study
of rucaparib, was expanded to enroll 41 patients with relapsed,
high-grade platinum-sensitive ovarian cancer associated with a
deleterious germline BRCA mutation. These patients had all received
2-4 prior treatment regimens, and had a progression-free interval
of six months or greater after their most recent platinum regimen.
Patients were treated with the recommended Phase 2 dose of 600mg
BID.
Consistent with the ARIEL2 data in BRCA-mutant patients, a
robust ORR was observed in this patient population. In 35 patients
evaluable for activity, 74 percent (26/35) of patients achieved a
RECIST and/or CA-125 response, and 66 percent (23/35) achieved a
RECIST response; a 77 percent disease control rate (DCR) was
observed. Robust activity was observed regardless of type of BRCA
mutation, length of progression-free interval between platinum
therapies and number of prior treatments: response rates (RECIST
and CA-125) ranged from 72 to 80 percent in those categories, or 61
to 78 percent for RECIST alone. Responses to rucaparib were
durable: 15 of 23 responses were still ongoing at time of analysis
with a median duration of response of over 11 months. Importantly,
77 percent of patients treated with at least 3 lines of
chemotherapy achieved a RECIST and/or CA-125 response, and 69
percent achieved a RECIST response. This is the subject population
of the ongoing ARIEL2 Extension registration study.
Rucaparib was well tolerated with a manageable safety profile;
the most common AEs were fatigue/asthenia, nausea and anemia. Any
Grade 3/4 AEs were successfully managed with dose modification. No
patients discontinued due to treatment-related adverse events.
ARIEL Pivotal Study Program
The ARIEL (Assessment of Rucaparib in Ovarian Cancer Trial)
program is a novel, integrated translational-clinical program
designed to accurately and prospectively identify patients with
tumor genotypes associated with benefit from rucaparib therapy.
- The global ARIEL2 study, initiated in
Q4 2013, has completed enrollment of approximately 200 ovarian
cancer patients with relapsed, platinum-sensitive disease. ARIEL2
is a two-part single-arm open label study. Part 1 is in
platinum-sensitive patients designed to identify pre-specified
tumor characteristics that predict sensitivity to rucaparib using
DNA sequencing to evaluate each patient’s tumor and provisional
results are described above. Part 2, referred to as the ARIEL2
Extension, is enrolling advanced ovarian cancer patients who have
received at least three prior chemotherapy regimens and will
evaluate clinical response in patients classified into
molecularly-defined subgroups, including germline BRCA-mutant,
somatic BRCA mutant and the BRCA-like signature, by a prospectively
defined genomic signature.
- The Phase 2 portion of Study 10, the
initial dose finding study, has been expanded to enroll an
additional 40 patients with relapsed, high-grade ovarian cancer
associated with a deleterious BRCA mutation (germline or somatic)
and who received ≥3 prior chemotherapy regimens.
- The ARIEL3 pivotal study is a
randomized, double-blind study comparing the effects of rucaparib
against placebo to evaluate whether rucaparib given as a
maintenance therapy to platinum-sensitive patients can extend the
period of time for which the disease is controlled after a positive
outcome with platinum-based chemotherapy. Patients are randomized
to receive either placebo or rucaparib and the primary endpoint of
the study is PFS. The primary efficacy analysis will evaluate, in a
step-down process, BRCA-mutant patients, all patients with a
BRCA-like signature (including BRCA and non-BRCA), and then all
patients.
In addition to the ARIEL program in ovarian cancer, the Company
is exploring rucaparib in other solid tumor types with significant
BRCA and BRCA-like populations.
Following on the recent Breakthrough Therapy designation status
of rucaparib by the FDA, data from the ARIEL2 study, if positive,
are expected to form the basis of a planned new drug application
(NDA) filing for treatment of advanced ovarian cancer in 2016.
Presentation Details
The oral presentation, titled, “Results of ARIEL2: A Phase 2
trial to prospectively identify ovarian cancer patients likely to
respond to rucaparib using tumor genetic analysis” is being
presented on Monday, June 1, during the Oral Abstract Session
titled, “Gynecologic Cancers”, from 8:00 to 11:00am CDT. (Abstract
5508)
The poster presentation, titled “A Phase 2 open-label,
multicenter study of single-agent rucaparib in the treatment of
patients with relapsed ovarian cancer and a deleterious BRCA
mutation” is being presented today during the Poster Session
titled, “Gynecologic Cancers”, from 1:15 to 4:45pm CDT and in the
subsequent poster discussion session from 4:45 to 6:00pm CDT.
(Abstract 5513; poster board 71)
The presentations will be made available online at that time at
www.clovisoncology.com.
Event Webcast Details
Clovis will host an investor/analyst event during ASCO on
Sunday, May 31st at 6:00pm CDT. The event will be simultaneously
webcast on the Company’s web site at www.clovisoncology.com, and
archived for future review.
About Rucaparib
Rucaparib is an oral, potent inhibitor of PARP1 and PARP2 being
developed for the treatment of advanced ovarian cancer in patients
with BRCA mutations (genes that are linked to breast and ovarian
cancers) and other DNA repair deficiencies.
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. For more information, please
visit our website at www.clovisoncology.com.
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 programs for our
drug candidates, the corresponding development pathways of our
companion diagnostics, actions by the FDA, the EMA or other
regulatory authorities regarding whether to approve drug
applications that may be filed, as well as their decisions
regarding drug labeling, and other matters that could affect the
availability or commercial potential of our drug candidates or
companion diagnostics, including competitive developments. Clovis
Oncology does not undertake to update or revise any forward-looking
statements. A further description of risks and uncertainties can be
found in Clovis Oncology’s filings with the Securities and Exchange
Commission, including its Annual Report on Form 10-K and its
reports on Form 10-Q and Form 8-K.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20150530005011/en/
Clovis OncologyAnna Sussman,
303-907-5358asussman@clovisoncology.comorBreanna Burkart,
303-907-5162bburkart@clovisoncology.com
Clovis Oncology (NASDAQ:CLVS)
Historical Stock Chart
From Mar 2024 to Apr 2024
Clovis Oncology (NASDAQ:CLVS)
Historical Stock Chart
From Apr 2023 to Apr 2024