- Data from the randomized, Phase 3 ARIEL4 study to be presented
today at the Society of Gynecologic Oncology Virtual Annual Meeting
on Women’s Cancer
- The ARIEL4 study met its primary endpoint, showing a
statistically significant improvement in investigator-assessed
progression-free survival (PFS) for Rubraca versus
chemotherapy
- The safety of Rubraca observed in the ARIEL4 study was highly
consistent with both the U.S. and EU product labels
Clovis Oncology, Inc. (NASDAQ: CLVS) announced that the first
presentation of data from the randomized, Phase 3 ARIEL4 study of
Rubraca® (rucaparib) will take place today in an oral
presentation at the Society of Gynecologic Oncology Virtual Annual
Meeting on Women’s Cancer (SGO). The data demonstrate that Rubraca
significantly improves PFS compared to standard-of-care
chemotherapy, including platinum-based chemotherapy, among patients
with advanced, relapsed ovarian cancer and a deleterious BRCA
mutation who have received two or more prior lines of
chemotherapy.
“Data from the ARIEL4 study meaningfully enhance our
understanding about the role of Rubraca among women with BRCA
mutation-positive relapsed ovarian cancer, as well as the clinical
relevance of BRCA reversion mutations,” said Dr. Rebecca
Kristeleit, Co-Coordinating Investigator of ARIEL4 and Consultant
Medical Oncologist, Guy’s and St Thomas’ NHS Foundation Trust,
London, UK. “This is important because women with more advanced
disease have fewer treatment options, and it is increasingly
important to understand how specific mutations affect treatment
outcomes.”
Dr. Kristeleit will present “Rucaparib versus chemotherapy in
patients with advanced, relapsed ovarian cancer and a deleterious
BRCA mutation: efficacy and safety from ARIEL4, a randomized phase
3 study” today during the SGO Scientific Plenary I: Innovation and
Progress in Gynecologic Oncology session from 2:35 pm - 3:45 pm CT.
The presentation can also be viewed at
https://www.clovisoncology.com/pipeline/scientific-presentations/
starting today at 2:35 pm CT.
The ARIEL4 study (NCT02855944) is a Phase 3 multicenter,
randomized study evaluating Rubraca versus chemotherapy in fully
platinum-sensitive, partially platinum-sensitive and
platinum-resistant patients with relapsed ovarian cancer and a BRCA
mutation (inclusive of germline and/or somatic) who have received
two or more prior lines of chemotherapy. The primary endpoint of
the study is investigator-assessed PFS, with a step-down analysis
from the primary efficacy population (if significant) to the
intent-to-treat (ITT) population.
The study enrolled 349 women in Europe, Israel and North and
South America. The primary efficacy population (n=325) comprised
the group of patients with a deleterious tumor BRCA mutation and
excluded those with a BRCA reversion mutation as determined by a
blood test. The rucaparib arm in this population (n=220) achieved
statistical significance over the chemotherapy arm (n=105) for the
primary endpoint of PFS with a hazard ratio of 0.64 (p=0.001). The
median PFS for the patients in the efficacy population treated with
rucaparib was 7.4 months versus 5.7 months among those who received
chemotherapy.
Additionally, in the ITT population (n=349), the rucaparib arm
(n=233) achieved statistical significance over the chemotherapy arm
(n=116) for the primary endpoint of PFS with a hazard ratio of 0.67
(p=0.002). The median PFS for the patients in the ITT population
treated with rucaparib was 7.4 months versus 5.7 months among those
who received chemotherapy.
Adverse events were consistent with the known safety profiles of
Rubraca and chemotherapy. The most common (>5%)
treatment-emergent ≥grade 3 adverse events (TEAEs) among all
patients treated with rucaparib (n=232) in the ARIEL4 study were
anemia/decreased hemoglobin (22%), neutropenia/decreased absolute
neutrophil count (10%), asthenia/fatigue (8%),
thrombocytopenia/decreased platelets (8%), and increased ALT/AST
(8%).
“The ARIEL4 data add to the growing scientific understanding
about the clinical utilization of Rubraca compared to chemotherapy,
including platinum-based chemotherapy, for women diagnosed with
BRCA mutation-positive advanced ovarian cancer,” said Patrick J.
Mahaffy, President and CEO of Clovis Oncology. “We remain committed
to expanding treatment options for patients living with cancer and
are pleased to share these data with physicians and their patients
to help improve outcomes for women with ovarian cancer.”
According to the American Cancer Society, an estimated more than
21,000 women will be diagnosed with ovarian cancer in the United
States and there will be an estimated nearly 14,000 deaths from
ovarian cancer in 2021, and according to GLOBOCAN in 2020, an
estimated 66,000 women in Europe are diagnosed each year with
ovarian cancer, and ovarian cancer is among those cancers with the
highest rate of deaths. According to the American Cancer Society,
more than 75% of women are diagnosed with ovarian cancer at an
advanced stage, and patients who are diagnosed with advanced
ovarian cancer have a 70-95% chance of recurrence according to the
Ovarian Cancer Research Alliance.
About Rubraca (rucaparib)
Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2
and PARP3 being developed in multiple tumor types, including
ovarian and metastatic castration-resistant prostate cancers, as
monotherapy, and in combination with other anti-cancer agents.
Exploratory studies in other tumor types are also underway.
Rubraca Ovarian Cancer U.S. FDA Approved Indications
Rubraca is indicated for the maintenance treatment of adult
women with recurrent epithelial ovarian, fallopian tube, or primary
peritoneal cancer who are in a complete or partial response to
platinum-based chemotherapy.
Rubraca is indicated for the treatment of adult women with a
deleterious BRCA mutation (germline and/or somatic)-associated
epithelial ovarian, fallopian tube, or primary peritoneal cancer
who have been treated with two or more chemotherapies. Select
patients for therapy based on an FDA-approved companion diagnostic
for Rubraca.
Select Important Safety Information
Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) have
occurred in patients treated with Rubraca, and are potentially
fatal adverse reactions. In 1146 treated patients, MDS/AML occurred
in 20 patients (1.7%), including those in long term follow-up. Of
these, 8 occurred during treatment or during the 28 day safety
follow-up (0.7%). The duration of Rubraca treatment prior to the
diagnosis of MDS/AML ranged from 1 month to approximately 53
months. The cases were typical of secondary MDS/cancer
therapy-related AML; in all cases, patients had received previous
platinum-containing regimens and/or other DNA damaging agents.
Do not start Rubraca until patients have recovered from
hematological toxicity caused by previous chemotherapy (≤ Grade 1).
Monitor complete blood counts for cytopenia at baseline and monthly
thereafter for clinically significant changes during treatment. For
prolonged hematological toxicities (> 4 weeks), interrupt
Rubraca or reduce dose and monitor blood counts weekly until
recovery. If the levels have not recovered to Grade 1 or less after
4 weeks or if MDS/AML is suspected, refer the patient to a
hematologist for further investigations, including bone marrow
analysis and blood sample for cytogenetics. If MDS/AML is
confirmed, discontinue Rubraca.
Based on its mechanism of action and findings from animal
studies, Rubraca can cause fetal harm when administered to a
pregnant woman. Apprise pregnant women of the potential risk to a
fetus. Advise females of reproductive potential to use effective
contraception during treatment and for 6 months following the last
dose of Rubraca.
Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1-4) were
nausea (76%), fatigue/asthenia (73%), abdominal pain/distention
(46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation
(38%), constipation (37%), vomiting (37%), diarrhea (32%),
thrombocytopenia (29%), nasopharyngitis/upper respiratory tract
infection (29%), stomatitis (28%), decreased appetite (23%), and
neutropenia (20%).
Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%;
Grade 1-4) were nausea (77%), asthenia/fatigue (77%), vomiting
(46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased
appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea
(21%), and thrombocytopenia (21%).
Co-administration of rucaparib can increase the systemic
exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may
increase the risk of toxicities of these drugs. Adjust dosage of
CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically
indicated. If co-administration with warfarin (a CYP2C9 substrate)
cannot be avoided, consider increasing frequency of international
normalized ratio (INR) monitoring.
Because of the potential for serious adverse reactions in
breast-fed children from Rubraca, advise lactating women not to
breastfeed during treatment with Rubraca and for 2 weeks after the
last dose.
Click here or full Prescribing Information and additional
Important Safety Information.
Rubraca (rucaparib) European Union (EU) authorized use and
Important Safety Information
Rubraca is indicated as monotherapy for the maintenance
treatment of adult patients with platinum-sensitive relapsed
high-grade epithelial ovarian, fallopian tube, or primary
peritoneal cancer who are in response (complete or partial) to
platinum-based chemotherapy.
Rubraca is indicated as monotherapy treatment of adult patients
with platinum sensitive, relapsed or progressive, BRCA mutated
(germline and/or somatic), high-grade epithelial ovarian, fallopian
tube, or primary peritoneal cancer, who have been treated with ≥2
prior lines of platinum-based chemotherapy, and who are unable to
tolerate further platinum-based chemotherapy.
Efficacy of Rubraca as treatment for relapsed or progressive
epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or
primary peritoneal cancer (PPC) has not been investigated in
patients who have received prior treatment with a PARP inhibitor.
Therefore, use in this patient population is not recommended.
Summary warnings and precautions:
Hematological toxicity
During treatment with Rubraca, events of myelosuppression
(anemia, neutropenia, thrombocytopenia) may be observed and are
typically first observed after 8–10 weeks of treatment with
Rubraca. These reactions are manageable with routine medical
treatment and/or dose adjustment for more severe cases. Complete
blood count testing prior to starting treatment with Rubraca, and
monthly thereafter, is advised. Patients should not start Rubraca
treatment until they have recovered from hematological toxicities
caused by previous chemotherapy (CTCAE grade ≥1).
Supportive care and institutional guidelines should be
implemented for the management of low blood counts for the
treatment of anemia and neutropenia. Rubraca should be interrupted
or dose reduced according to Table 1 (see Posology and Method of
Administration [4.2] of the Summary of Product Characteristics
[SPC]) and blood counts monitored weekly until recovery. If the
levels have not recovered to CTCAE grade 1 or better after 4 weeks,
the patient should be referred to a hematologist for further
investigations.
MDS/AML
MDS/AML, including cases with fatal outcome, have been reported
in patients who received Rubraca. The duration of therapy with
Rubraca in patients who developed MDS/AML varied from less than 1
month to approximately 28 months.
If MDS/AML is suspected, the patient should be referred to a
hematologist for further investigations, including bone marrow
analysis and blood sampling for cytogenetics. If, following
investigation for prolonged hematological toxicity, MDS/AML is
confirmed, Rubraca should be discontinued.
Photosensitivity
Photosensitivity has been observed in patients treated with
Rubraca. Patients should avoid spending time in direct sunlight
because they may burn more easily during Rubraca treatment; when
outdoors, patients should wear a hat and protective clothing, and
use sunscreen and lip balm with sun protection factor of 50 or
greater.
Gastrointestinal toxicities
Gastrointestinal toxicities (nausea and vomiting) are frequently
reported with Rubraca, and are generally low grade (CTCAE grade 1
or 2), and may be managed with dose reduction (refer to Posology
and Method of Administration [4.2], Table 1 of the SPC) or
interruption. Antiemetics, such as 5-HT3 antagonists,
dexamethasone, aprepitant and fosaprepitant, can be used as
treatment for nausea/vomiting and may also be considered for
prophylactic (i.e. preventative) use prior to starting Rubraca. It
is important to proactively manage these events to avoid prolonged
or more severe events of nausea/vomiting which have the potential
to lead to complications such as dehydration or
hospitalization.
Embryofetal toxicity
Rubraca can cause fetal harm when administered to a pregnant
woman based on its mechanism of action and findings from animal
studies. In an animal reproduction study, administration of Rubraca
to pregnant rats during the period of organogenesis resulted in
embryo-fetal toxicity at exposures below those in patients
receiving the recommended human dose of 600 mg twice daily (see
Preclinical Safety Data [5.3] of the SPC).
Pregnancy/contraception
Pregnant women should be informed of the potential risk to a
fetus. Women of reproductive potential should be advised to use
effective contraception during treatment and for 6 months following
the last dose of Rubraca (see section 4.6 of the SPC). A pregnancy
test before initiating treatment is recommended in women of
reproductive potential.
Click here to access the current SPC. Healthcare professionals
should report any suspected adverse reactions via their national
reporting systems.
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, for
those indications that require them, 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, with additional office locations in the U.S. and
Europe. Please visit www.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. Examples of forward-looking
statements contained in this press release include, among others,
statements regarding the potential results of such clinical trials,
our expectations regarding the suitability of Rubraca for certain
patient populations or indications, and our plans to develop
Rubraca in additional indications and tumor types, and our
expectations regarding the outcomes of early studies or trials
supporting further development, both non-clinical and clinical.
Such forward-looking statements involve substantial risks and
uncertainties that could cause our 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 our clinical
development programs for our drug candidates and those of our
partners, whether future study results will be consistent with
study findings to date, the timing of availability of data from our
clinical trials and the initiation, enrollment, timing and results
of our planned clinical trials and the corresponding development
pathways, effectiveness and suitability of diagnostic tests, the
risk that final results of ongoing trials may differ from initial
or interim results as a result of factors such as final results
from a larger patient population may be different from initial or
interim results from a smaller patient population, the risk that
additional pre-clinical or clinical studies may not support further
development in certain additional indications or tumor types, and
actions by the FDA, the EMA or other regulatory authorities
regarding data required to support drug applications and whether to
approve drug applications. 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: https://www.businesswire.com/news/home/20210319005072/en/
Clovis Investor Contacts: Anna Sussman, 303.625.5022
asussman@clovisoncology.com or Breanna Burkart, 303.625.5023
bburkart@clovisoncology.com
Clovis Media Contacts: U.S. Lisa Guiterman, 301.217.9353
clovismedia@sambrown.com
Europe Jake Davis, +44 (0) 20.3946.3538
Jake.Davis@publicisresolute.com
Clovis Oncology (NASDAQ:CLVS)
Historical Stock Chart
From Aug 2024 to Sep 2024
Clovis Oncology (NASDAQ:CLVS)
Historical Stock Chart
From Sep 2023 to Sep 2024