Categorynews

Expanded Rubraca® (Rucaparib) Data from Clovis Oncology’s ARIEL3 and TRITON2 Trials in Ovarian and Prostate Cancers to be Presented at 2019 ASCO Annual Meeting

June 1, 2019 Off By BusinessWire

In exploratory analysis of ARIEL3 data, Rubraca significantly
improved clinically meaningful endpoints including chemotherapy free
interval and PFS on next therapy line for women with advanced ovarian
cancer in maintenance treatment setting
Updated Rubraca safety profile was consistent with the safety
profile previously observed in ARIEL3
TRITON2 findings show that tumor tissue and plasma assays
successfully identified patients with a DNA damage repair gene mutation
Responses to Rubraca were observed in TRITON2 patients with
germline or somatic BRCA1/2 mutations
Two investigator-initiated studies highlighting the potential of
Rubraca in multiple cancer types also presented

BOULDER, Colo.–(BUSINESS WIRE)–$CLVS–Clovis Oncology, Inc. (NASDAQ: CLVS) today announced multiple datasets
being presented at the 2019 American Society of Clinical Oncology (ASCO)
Annual Meeting in Chicago, May 31 – June 4, 2019. These include
presentations of exploratory endpoint evaluations and updated safety
data from the pivotal Phase 3 ARIEL3 trial evaluating Rubraca^®
(rucaparib) for the maintenance treatment of advanced ovarian cancer, as
well as genomic characteristics of BRCA1/2 mutations among metastatic
castration-resistant prostate cancer (mCRPC) patients in the Phase 2
TRITON2 trial evaluating Rubraca in mCRPC.

“The breadth and depth of data from both company and
investigator-sponsored Rubraca trials presented at this year’s ASCO
meeting demonstrate the growing strength of the data and clinical
development programs behind Rubraca,” said Patrick J. Mahaffy, President
and CEO of Clovis Oncology. “Accordingly, we look forward to presenting
updated clinical data from the TRITON2 study at an upcoming medical
conference in the second half of 2019 and submitting our planned
supplemental NDA filing for BRCA-mutant advanced prostate cancer in Q4
2019.”

ARIEL3 Exploratory Endpoints and Updated Safety
Data

During an afternoon session on Saturday, June 1, Robert L. Coleman, MD,
professor of Gynecologic Oncology and Reproductive Medicine, The
University of Texas MD Anderson Cancer Center in Houston and
co-coordinating investigator in the ARIEL3 clinical trial program, will
present the poster “Exploratory analysis of the effect of maintenance
rucaparib on post-progression outcomes in patients with
platinum-sensitive recurrent ovarian carcinoma and updated safety data
from the phase 3 study ARIEL3” (Abstract #5522/Poster Board #345).

Data from this analysis of the ARIEL3 trial, which enrolled patients
with platinum-sensitive recurrent ovarian carcinoma, demonstrated that
Rubraca significantly improved the clinically meaningful exploratory
endpoints of chemotherapy-free interval (CFI), time to start of first
subsequent therapy (TFST), time to investigator-assessed progression on
the subsequent line of treatment or death (PFS2), and time to second
subsequent therapy (TSST) vs. placebo.

The updated safety profile generated in this analysis is consistent with
the previously-reported primary efficacy data analysis based on a data
cutoff date of April 15, 2017. As of December 31, 2017, the most common
treatment-emergent adverse events (TEAEs) of any grade (rucaparib vs.
placebo) were nausea (75.8% vs. 36.5%), asthenia/fatigue (70.7% vs.
44.4%), dysgeusia (39.8% vs. 6.9%), and anemia/decreased hemoglobin
(39.0% vs. 5.3%). The most common grade ≥3 TEAEs were anemia/decreased
hemoglobin (21.5% vs. 0.5%) and alanine/aspartate aminotransferase
increase (10.2% vs. 0.0%).

“These data positively reinforce our current clinical utilization and
understanding of rucaparib as maintenance treatment for women with
advanced ovarian cancer,” said Dr. Coleman. “They provide further
confirmation that rucaparib may help women and their physicians sustain
a response to platinum-based chemotherapy.”

Genomic Characteristics of BRCA1/2
Alterations in Patients with mCRPC Enrolled in TRITON2

Also on Saturday, June 1, Wassim Abida, MD, Medical Oncologist, Memorial
Sloan Kettering Cancer Center, and coordinating investigator for the
TRITON2 study, will present the poster “Genomic characteristics of
deleterious BRCA1 and BRCA2 alterations and associations
with baseline clinical factors in patients with metastatic
castration-resistant prostate cancer (mCRPC) enrolled in TRITON2”
(Abstract #5031/Poster Board #143).

The ongoing phase 2 TRITON2 (NCT02952534) study is evaluating the
poly(ADP-ribose) polymerase inhibitor rucaparib in mCRPC patients
harboring a deleterious germline or somatic mutation in BRCA1, BRCA2,
ATM, or other DNA damage repair (DDR) genes as determined by central
screening of tumor tissue or plasma, or from local testing.
Next-generation sequencing (NGS) assays evaluating tumor tissue and
circulating cell-free tumor DNA (ctDNA) in plasma were both used to
successfully identify patients with eligible alterations in BRCA1/2.
The plasma assay is minimally invasive and reliably detects alterations
in patients with disease that is difficult to biopsy.

In this analysis, associations between baseline genomic and clinical
characteristics were assessed. Several findings support the hypothesis
that germline BRCA1/2 alterations are a prognostic factor in prostate
cancer associated with more rapid progression to advanced disease.
Patients with germline BRCA1/2 alterations were younger at time of
enrollment into TRITON2, had more advanced disease at time of diagnosis
and had a shorter time between diagnosis and enrollment into TRITON2 as
compared to patients with somatic BRCA1/2 alterations. However,
responses to rucaparib were observed in patients with germline or
somatic BRCA1/2 alterations, highlighting the potential of rucaparib to
benefit both groups of patients.

Today’s poster includes the confirmed objective response rate (ORR) data
based on the same June 29, 2018 visit cut-off date presented at ESMO
2018 and presents those data by germline or somatic BRCA1/2 mutation
status. By investigator-assessed RECIST/PCWG3, the confirmed ORR in
patients with a germline or somatic BRCA1/2 mutation treated with
Rubraca was 50% (5/10) or 40% (6/15), respectively. By PSA response, the
confirmed ORR in patients with a germline or somatic BRCA1/2 mutation
treated with Rubraca was 66.7% (10/15) or 43.3% (13/30), respectively.

“These data reinforce the importance of genomic testing to inform
clinical decision making, including consideration of plasma testing in
patients with mCRPC,” said Dr. Abida. “Clinicians are increasingly
reliant on a patient’s unique genomic profile to determine therapeutic
options, especially as targeted agents such as PARP inhibitors advance
toward additional approved indications.”

The Clovis-sponsored ASCO posters will be available online at http://clovisoncology.com/pipeline/scientific-presentations/
as of the time they are presented at the meeting.

Additional Rubraca Poster Presentations:
Investigator-Initiated Trials

Two trials in progress posters describe investigator-initiated studies
that were selected for poster presentations at the 2019 ASCO Annual
Meeting. These include a multi-center Phase 2 trial of rucaparib in
combination with nivolumab as maintenance therapy for patients with
advanced biliary tract cancer (Abstract #TPS4153/Poster Board #252a) to
be presented on Monday, June 3 from 8:00-11:00am CDT in Hall A; and a
Phase 1b/2a study of rucaparib combined with nivolumab in mCRPC and
advanced/recurrent endometrial cancer (Abstract #TPS2663/Poster Board
#297b) presented today from 8:00-11:00am CDT in Hall A.

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 the TRITON2 Clinical Trial

TRITON2 is an international, multicenter, open-label Phase 2 study of
Rubraca in men with metastatic castration-resistant prostate cancer with
BRCA gene alterations (inclusive of germline or somatic), which is also
enrolling patients with deleterious alterations of other DNA damage
repair (DDR) genes, including ATM. The study is currently enrolling
across sites worldwide. For more information, please visit www.tritontrials.com.

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.

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 1,100 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, 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 our expectations for submission of regulatory filings, our
plans for presentation of data from ongoing trials, our expectations
regarding ongoing or planned trials and the timing and pace of
commencement of and enrollment in our clinical trials, including those
being considered, planned or conducted in collaboration with
partners. 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 and
whether future study results will support continued development or
regulatory approval, the corresponding development pathways of our
companion diagnostics, the timing of availability of data from our
clinical trials and the results, the initiation, enrollment, timing and
results of our planned clinical trials. 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.