Clovis Oncology to Highlight Rubraca® (rucaparib) Data from Post-Hoc ARIEL3 Analyses at SGO 2019 Congress

March 16, 2019 Off By BusinessWire

- Exploratory analyses of ARIEL3 Rubraca data in recurrent ovarian
  cancer presented in oral plenary and poster sessions

- Maintenance treatment with Rubraca improved median progression-free
  survival (PFS) and reduced the risk of progression vs placebo
  regardless of age subgroup

- Maintenance treatment with Rubraca significantly improved PFS and
  reduced the risk of progression vs placebo regardless of whether
  tumors had deleterious germline BRCA mutations

Safety profile of Rubraca was consistent with the overall safety
population previously reported

BOULDER, Colo.–(BUSINESS WIRE)–lt;a href=”https://twitter.com/search?q=%24CLVS&src=ctag” target=”_blank”gt;$CLVSlt;/agt; lt;a href=”https://twitter.com/hashtag/SGO2019?src=hash” target=”_blank”gt;#SGO2019lt;/agt;–Clovis Oncology, Inc. (NASDAQ: CLVS) today announced that data from post
hoc exploratory analyses from the ARIEL3 Phase 3 clinical study of
Rubraca will be presented during oral plenary and poster sessions at the
Society of Gynecologic Oncology 2019 Congress (SGO), March 16 -19, 2019
in Honolulu, Hawaii. Data to be presented will highlight ARIEL3 results
in different patient demographics, including age and deleterious
germline mutation status.

“The results from these post hoc analyses of the ARIEL3 study data
underscore the safety and efficacy of Rubraca across a broad range of
women with recurrent ovarian cancer,” said Patrick J. Mahaffy, President
and CEO of Clovis Oncology. “We hope that our continuing exploration,
analysis and publication of ARIEL3 data will help inform treatment
decisions as well as the management of advanced ovarian cancer.”

Included in the SGO 2019 Congress Scientific Plenary 1 session is the
following:

Title: The effect of age on efficacy and safety outcomes with rucaparib:
a post hoc exploratory analysis of ARIEL3, a phase 3, randomized,
placebo-controlled maintenance study in patients with recurrent ovarian
carcinoma

Presenter: Jonathan A. Ledermann

Session: Scientific Plenary I: Snap, Crackle, PARP

Date/Time: March 16, 2019; 6:45 – 7:45am (HST) // 12:45 – 11:45pm (EDT)

Location: Kamehameha 3

Summary: The efficacy and safety of Rubraca maintenance treatment was
investigated in three age-based sub-groups from ARIEL3 in a post-hoc
exploratory analysis. In the intent-to-treat (ITT) population,
investigator-assessed median PFS for patients aged <65 years was 11.1
months (n=237) in the Rubraca arm vs 5.4 months (n=117) in the placebo
arm (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.25–0.43);
for patients aged 65–74 years, median PFS was 8.3 months (n=113) vs 5.3
months (n=64) (HR, 0.43; 95% CI, 0.29–0.64); and for patients aged ≥75
years, median PFS was 9.2 months (n=25) vs 5.5 months (n=8) (HR, 0.47;
95% CI, 0.16–1.35).

In this dataset, maintenance treatment with Rubraca improved median PFS
and reduced the risk of progression vs placebo regardless of age
subgroup. In general, the safety profile of Rubraca was consistent
across the three age subgroups.

“As we continue to explore and expand our use of PARP inhibitors for the
maintenance treatment of recurrent ovarian cancer, it’s helpful for
physicians to know how individual factors such as patient age may impact
treatment decisions,” said Professor Jonathan Ledermann, MD, Professor
of Medical Oncology, UCL Cancer Institute and UCL Hospitals, London,
Global Principal Investigator for non-US sites in the ARIEL3 study. “In
our analysis of the ARIEL3 study, we found that maintenance treatment
with Rubraca improved median PFS, reduced the risk of progression and
had a consistent safety profile regardless of age, suggesting that
patient age should not discourage physicians from considering Rubraca in
this setting.”

Included in an SGO 2019 Congress poster presentation session is the
following:

Title: Post hoc exploratory analysis of rucaparib in patients with
platinum-sensitive recurrent ovarian carcinoma from the randomized,
placebo-controlled phase 3 study ARIEL3: effect of a deleterious
germline or no germline BRCA mutation on efficacy and safety

Presenter: Robert L. Coleman

Date/Time: March 18, 2019; 6:00 – 10:00am and 3:30 – 5:00pm (HST)//
12:00 – 4:00pm and 9:30 –11pm (EDT)

Location: Kamehameha 2

Summary: For this analysis, researchers assessed PFS in the subgroup of
patients with a deleterious germline BRCA mutation (germline BRCA
mutation) and in patients without a deleterious germline BRCA mutation
(no germline BRCA mutation). In these subgroups, Rubraca significantly
improved PFS vs placebo regardless of BRCA mutation status. Although the
reduction in risk was numerically greater in the germline BRCA mutation
subgroup (hazard ratio [HR], 0.25; 95% confidence interval [CI],
0.16–0.39) than in the no germline BRCA mutation subgroup (HR, 0.41; 95%
CI, 0.32–0.52), the reduction in risk between the two subgroups did not
differ by a statistically significant margin. The safety profile of
Rubraca vs placebo in the germline BRCA mutation and no germline BRCA
mutation subgroups was consistent with the safety profile of Rubraca in
the overall safety population reported previously.

This post hoc exploratory analysis demonstrated that the reduction in
risk was numerically greater in the germline BRCA mutation subgroup than
in the no germline BRCA mutation subgroup. In the no germline BRCA
mutation subgroup, the observed improvement in PFS was not driven solely
by the somatic BRCA mutation + wild-type BRCA/high LOH subgroup as
demonstrated by the analysis of patients with wild-type BRCA tumors.

“While it is evident that women whose tumors possess a BRCA mutation
derive the greatest benefit from rucaparib therapy, the data presented
in this poster demonstrate the meaningful and clinically relevant
benefit that eligible patients, including those without a BRCA mutation,
may receive as a result of maintenance treatment,” said Robert L.
Coleman, MD, Professor, Gynecologic Oncology and Reproductive
Medicine at The University of Texas MD Anderson Cancer
Center in Houston and co-Coordinating Investigator in the ARIEL3
clinical trial program. “These data further reinforce the importance of
maintenance treatment for women with recurrent ovarian cancer versus the
previous standard of observation following treatment with chemotherapy.”

About the ARIEL3 Clinical Trial

The ARIEL3 pivotal study of rucaparib is a confirmatory randomized,
double-blind study comparing the effects of rucaparib against placebo to
evaluate whether rucaparib given as a maintenance treatment to
platinum-sensitive ovarian cancer patients can extend the period of time
for which the disease is controlled after a complete or partial response
to platinum-based chemotherapy. The study enrolled 564 patients with
high-grade epithelial ovarian, fallopian tube or primary peritoneal
cancer. To be eligible for the study, participants had to have received
at least two prior platinum-based treatment regimens, been sensitive to
the penultimate platinum regimen, and achieved a complete or partial
response to their most recent platinum-based regimen. There were no
genomic selection criteria for this study. Trial participants were
randomized 2:1 to receive 600 milligrams of rucaparib twice daily (BID)
or placebo. The study achieved its primary endpoint of improved PFS by
investigator review in each of three populations. PFS was also improved
in the rucaparib group compared with placebo by independent review, a
key secondary endpoint, in all three populations. In addition, rucaparib
improved objective response rate vs placebo among evaluable trial
participants in all three study populations.

About Rubraca^® (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3
being developed in multiple tumor types, including ovarian, metastatic
castration-resistant prostate, and bladder cancers, as monotherapy, and
in combination with other anti-cancer agents. Exploratory studies in
other tumor types are also underway.

Clovis holds worldwide rights for Rubraca. Rubraca is an unlicensed
medical product outside of the U.S. and the EU.

Rubraca U.S. FDA Approved Indications and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of
adult patients 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 as monotherapy for the treatment of adult patients
with deleterious BRCA mutations (germline and/or
somatic) associated epithelial ovarian, fallopian tube, or primary
peritoneal cancer who have been treated with two or more chemotherapies
and selected for therapy based on an FDA-approved companion diagnostic
for Rubraca.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur
uncommonly in patients treated with Rubraca, and are potentially fatal
adverse reactions. In approximately 1100 treated patients, MDS/AML
occurred in 12 patients (1.1%), including those in long-term follow-up.
Of these, five occurred during treatment or during the 28-day safety
follow-up (0.5%). The duration of Rubraca treatment prior to the
diagnosis of MDS/AML ranged from 1 month to approximately 28 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 (see Dosage and Administration [2.2] in full Prescribing
Information) 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
cytogenetic analysis. 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 laboratory abnormalities in ARIEL3 (≥ 25%; Grade 1–4) were
increase in creatinine (98%), decrease in hemoglobin (88%), increase in
cholesterol (84%), increase in alanine aminotransferase (ALT) (73%),
increase in aspartate aminotransferase (AST) (61%), decrease in
platelets (44%), decrease in leukocytes (44%), decrease in neutrophils
(38%), increase in alkaline phosphatase (37%) and decrease in
lymphocytes (29%).

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%).

Most common laboratory abnormalities in Study 10 and ARIEL2 (≥ 35%;
Grade 1–4) were increase in creatinine (92%), increase in alanine
aminotransferase (ALT) (74%), increase in aspartate aminotransferase
(AST) (73%), decrease in hemoglobin (67%), decrease in lymphocytes
(45%), increase in cholesterol (40%), decrease in platelets (39%) and
decrease in absolute neutrophil count (35%).

Co-administration of Rubraca 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. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You
may also report side effects to Clovis Oncology, Inc. at 1-844-258-7662.

Click
here for full Prescribing Information and additional Important
Safety Information.

Rubraca^®▼ (rucaparib) EU Authorized Use and
Important Safety Information

Rucaparib 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.

Rucaparib 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 two or more prior
lines of platinum-based chemotherapy, and who are unable to tolerate
further platinum-based chemotherapy.

Summary warnings and precautions: Haematological toxicity:
Patients should not start Rubraca until they have recovered from
haematological toxicities caused by previous chemotherapy (≤ CTCAE Grade
1). Complete blood count testing prior to starting treatment with
Rubraca and monthly thereafter is advised. Rubraca should be interrupted
or dose reduced and blood counts monitored weekly until recovery for the
management of low blood counts. Myelodysplastic syndrome/acute myeloid
leukaemia (MDS/AML): If MDS/AML is suspected, the patient should be
referred to a haematologist for further investigation. If MDS/AML is
confirmed, Rubraca should be discontinued. Photosensitivity: Patients
should avoid spending time in direct sunlight as they may burn more
easily. When outdoors, patients should wear protective clothing and
sunscreen with SPF of 50 or greater. Gastrointestinal toxicities: Low
grade (CTCAE Grade 1 or 2) nausea and vomiting may be managed with dose
reduction or interruption. Additionally, antiemetics may be considered
for treatment or prophylaxis.

Click
here to access the current Summary of Product Characteristics.
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, 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; please visit www.clovisoncology.com
for more information, including additional office locations in the U.S.
and Europe.

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 our expectations to make Rubraca available to additional
eligible patients. 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, the risk that results of further
trials may differ from initial or interim results, or post-hoc analyses,
as a result of many factors, including final results from a larger
patient population differing from initial or interim results from a
smaller patient population, and the uncertainties inherent in actions by
the FDA, the EMA or other regulatory authorities regarding data required
to support drug applications and whether to accept or approve drug
applications that may be filed, as well as their decisions regarding
drug labeling, reimbursement and pricing. 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.