- New rucaparib data presented today in
two oral plenary sessions
- Data provide additional insights from
ARIEL2 Phase 2 study of rucaparib in advanced ovarian cancer
- FDA approved Rubraca® (rucaparib)
tablets in December 2016 as monotherapy treatment for women with
BRCA-mutated advanced ovarian cancer based on data from Study 10
and ARIEL2
Clovis Oncology, Inc. (NASDAQ:CLVS) announced new data from
parts 1 and 2 of the ongoing ARIEL2 Phase 2 study being presented
today at the 2017 Society of Gynecologic Oncology (SGO) Annual
Meeting on Women’s Cancer in National Harbor, MD.
The data are being presented in two oral plenary sessions:
- Title: Rucaparib in patients
with relapsed, primary platinum-sensitive high-grade ovarian
carcinoma with germline or somatic BRCA mutations: Integrated
summary of efficacy and safety from the phase 2 study
ARIEL2Time: Sunday, March 12 at 8:22-8:37 a.m.
ESTPresenter: Gottfried Konecny, MD, associate professor of
Medicine, Department of Medicine, David Geffen School of Medicine,
UCLA, Los Angeles, CASGO selected this abstract as the recipient
of the 2017 SGO Presidential Award
- Title: BRCA1 and RAD51C promoter
hypermethylation confer sensitivity to the PARP inhibitor rucaparib
in patients with relapsed, platinum sensitive ovarian carcinoma in
ARIEL2 part 1Time: Sunday, March 12 at 10:30-10:40 a.m.
ESTPresented By: Elizabeth Swisher, MD, University of
Washington Medical Center, Seattle, WA
New data from these presentations include analyses of patient
subsets from the ARIEL2 trial, including an integrated summary of
data in patients from ARIEL2 parts 1 and 2 with a germline or
somatic BRCA1 or BRCA2 (BRCA) mutation. ARIEL2 enrolled 493
patients with relapsed ovarian cancer to identify those patients
most likely to respond to treatment with rucaparib: part 1 enrolled
206 patients who received one or more prior therapies, had platinum
as their last treatment, and were platinum-sensitive; part 2
enrolled 287 patients treated with three or four prior therapies
who were either platinum-sensitive, -resistant or -refractory at
time of enrollment.
“These results demonstrate the impressive activity of rucaparib,
especially in earlier line, platinum-sensitive patients,” said Dr.
Konecny. “We also gain insight into important biomarker analyses
that may help us predict which patients with far more advanced
disease are most likely to benefit from rucaparib.”
Dr. Konecny’s presentation analyzed objective response rate
(ORR) and progression-free survival (PFS) in the 134 ovarian cancer
patients with a germline or somatic BRCA mutation enrolled in
ARIEL2, as well as the effect of platinum sensitivity status and
prior lines of therapy on these endpoints. These data demonstrate
that the objective response rate (ORR), disease control rate (DCR)
and median progression-free survival (PFS) in patients with a BRCA
mutation were greatest in platinum-sensitive patients, followed in
descending order by those who were platinum-resistant, and those
who were platinum-refractory. All responses were assessed and
confirmed according to RECIST. DCR in ARIEL2 was defined as the
percentage of patients who had achieved either a complete response,
partial response or stable disease that was maintained for greater
than 12 weeks. Patients with disease progression occurring at least
6 months after last platinum were considered platinum-sensitive;
patients with disease progression occurring less than 6 months
after last platinum with best response other than progressive
disease (PD) were considered platinum-resistant; and patients with
best response of PD on last platinum which occurred during or up to
2 months after treatment were considered platinum-refractory. The
data analysis cutoff date was January 4, 2017 and this analysis was
limited to patients with BRCA-mutated ovarian cancer enrolled in
the ARIEL2 study.
In 57 platinum-sensitive patients whose immediate prior therapy
was platinum-based, the investigator-assessed ORR was 70% (95% CI:
57-72) for the overall population, with 83% (95% CI: 59-96), 86%
(95% CI: 57-98) and 52% (95% CI: 31-72) ORR observed in patients
treated with one, two, or three or more prior lines, respectively.
The DCR in the same population was 81% (95% CI: 68-90) for the
overall population, with 94% (95% CI: 73-100), 86% (95% CI: 57-98)
and 68% (95% CI: 47-85) in patients treated with one, two, or three
or more prior lines, respectively. The median PFS in the overall
platinum-sensitive population whose immediate prior therapy was
platinum-based was 12.7 months (95% CI: 9.0-14.7; 30%
censoring).
In addition, PFS and ORR were assessed by BRCA mutation type in
platinum-sensitive patients whose immediate prior treatment was
platinum. Patients with a germline or somatic BRCA mutation had
ORRs of 75% (95% CI: 57-89) and 74% (95% CI: 49-91), and median PFS
of 12.8 and 12.7 months, respectively (95% CI: 8.9-16.6; 31%
censoring and 6.2-18.2; 21% censoring). Patients with a BRCA
mutation had ORRs of 71% (95% CI: 53-85) and 70% (95% CI: 47-87),
and median PFS of 12.8 and 11.2 months, respectively (95% CI:
8.1-18.2; 26% censoring and 7.3-16.6; 35% censoring).
All evaluable platinum-resistant and -refractory patients had
been treated with three or more lines of therapy. In 49
platinum-resistant patients, the ORR was 25% (95% CI: 13-39), the
DCR was 39% (95% CI: 25-54), and the median PFS was 7.3 months (95%
CI: 5.5-7.7; 27% censoring). In 14 platinum-refractory patients,
there were no responders, consistent with data previously presented
at the 2016 ESMO Annual Meeting. However, the DCR was 29% (95% CI:
8-58) and the median PFS was 5.0 months (95% CI: 1.9-5.7; 21%
censoring).
Dr. Konecny’s presentation also discussed the potential role of
secondary somatic mutations restoring BRCA function as a mechanism
of platinum resistance in patients with platinum-resistant or
-refractory disease. Published data have shown that secondary
mutations in BRCA are more frequently observed in
platinum-resistant patients than platinum-sensitive patients. Data
presented show that the presence of secondary somatic BRCA
mutations may be a better predictor of rucaparib efficacy than
prior responsiveness to platinum-based chemotherapy in patients
with platinum-resistant or -refractory disease. In 55 evaluable
patients with platinum-resistant or -refractory disease, those
without a secondary somatic BRCA mutation (n=47) achieved a median
PFS of 7.3 months (95% CI: 5.4-9.0; 26% censoring); conversely,
eight patients with a secondary somatic mutation demonstrated a
median PFS of only 1.7 months (95% CI: 1.6-3.2; 0% censoring).
These secondary mutations were identified by sequencing of
screening tumor biopsy and/or circulating tumor DNA (ctDNA)
analysis.
The most common treatment-emergent adverse events observed in
ARIEL2 included nausea (78%), asthenia/fatigue (78%), and vomiting
(49%). The most common treatment-emergent grade 3/4 adverse events
observed in ARIEL2 included anemia/decreased hemoglobin (29%),
ALT/AST increased (10%), and asthenia/fatigue (10%).
Treatment-emergent adverse events led to dose reductions in 49% of
patients, and treatment discontinuation in 13% of patients.
In the second presentation today, Dr. Swisher discussed an
analysis of BRCA1 and RAD51C hypermethylation among archival and
pretreatment biopsies from part 1 of the ARIEL2 study. The analysis
demonstrated that, among ovarian cancer patients, methylation of
BRCA1 and RAD51C is associated with high loss of heterozygosity
(LOH), consistent with the HRD phenotype. Further, methylation of
BRCA1 and RAD51C appear to confer sensitivity to rucaparib, as do
mutations of CDK12. These data suggest that methylation is more
reliably assessed in pretreatment than archival tumor samples. Dr.
Swisher concludes that routine sequencing of high-grade ovarian
cancer tumor tissue biopsies would identify at least 10-15% of
women with a somatic mutation and 20% of women with a germline
mutation whose tumors might be sensitive to rucaparib.
“We are pleased to present these additional data from the ARIEL2
trial and are encouraged that these findings continue to reinforce
rucaparib’s activity and safety profile in the treatment of
patients with advanced ovarian cancer,” said Patrick J. Mahaffy,
CEO and president of Clovis Oncology. “The data presented today
demonstrate our continued commitment to investing in and conducting
the rigorous scientific research that will help us and physicians
better understand the patients who can benefit most significantly
from treatment with rucaparib.”
The presentations are available online at
http://clovisoncology.com/pipeline/scientific-presentations/ as of
the time of Dr. Swisher’s presentation at the Meeting.
About Rubraca® (rucaparib) tablets
Rubraca is a PARP inhibitor indicated as monotherapy for the
treatment of patients with deleterious BRCA mutation
(germline and/or somatic) associated advanced ovarian cancer, who
have been treated with two or more chemotherapies, and selected for
therapy based on an FDA-approved companion diagnostic for
Rubraca. The indication for Rubraca is approved under the FDA’s
accelerated approval program based on objective response rate and
duration of response, and is based on results from two multicenter,
single-arm, open-label clinical trials. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in confirmatory trials. Please
visit rubraca.com for more information.
About Rucaparib
Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2
and PARP3 being developed in ovarian cancer as well as several
additional solid tumor indications. The MAA submission
in Europe for an ovarian cancer treatment indication was
submitted and accepted during the fourth quarter of 2016.
Additionally, rucaparib is being developed as maintenance therapy
for ovarian cancer in the ARIEL3 trial for patients with tumors
with BRCA mutations and other DNA repair deficiencies beyond BRCA,
as well as biomarker negative patients. Data from ARIEL3 are
expected in mid-2017, which, pending positive data, is expected to
be followed by the submission of a supplemental NDA for a second
line or later maintenance indication. Rucaparib is also being
developed in patients with mutant BRCA tumors and other DNA repair
deficiencies beyond BRCA – commonly referred to as homologous
recombination deficiencies, or HRD. Studies open for enrollment or
under consideration include prostate, breast, pancreatic,
gastroesophageal, bladder and lung cancers. Clovis holds worldwide
rights for rucaparib.
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, with partners, diagnostic tools intended
to 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.
Please visit clovisoncology.com for more information.
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 that expressed or implied by the forward-looking statements.
Such risks and uncertainties include, among others, the
uncertainties inherent in whether future study results will be
consistent with study findings to-date, the clinical development
programs for our drug candidates and expectations with respect to
regulatory submissions and approvals. 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/20170312005019/en/
Investor/Analyst:For Clovis Oncology, Inc.Anna Sussman,
303-625-5022asussman@clovisoncology.comorBreanna Burkart,
303-625-5023bburkart@clovisoncology.com
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