Rubraca is the first PARP inhibitor approved in
a prostate cancer setting
Accelerated approval based on objective
response rate (ORR) and duration of response (DOR) data from the
TRITON2 clinical triali
44% ORR (95% CI 31, 57) and median DOR not
evaluable (95% CI 6.4, NE, range in months at data cutoff
1.7-24.0+) by blinded independent radiologic review (IRR)i
Most common Grade 3-4 adverse reaction was
anemia; most common Grade 3-4 lab abnormality was decrease in
hemoglobini
Clovis Oncology, Inc. (NASDAQ: CLVS), announced today that the
U.S. Food and Drug Administration (FDA) approved Rubraca®
(rucaparib) tablets for the treatment of adult patients with a
deleterious BRCA mutation (germline and/or somatic)-associated
metastatic castration-resistant prostate cancer (mCRPC) who have
been treated with androgen receptor-directed therapy and a
taxane-based chemotherapy. The FDA approved this indication under
accelerated approval based on objective response rate (ORR) and
duration of response (DOR) data from the multi-center, single arm
TRITON2 clinical trial. Continued approval for this indication may
be contingent upon verification and description of clinical benefit
in confirmatory trials. The TRITON3 clinical trial is expected to
serve as the confirmatory study for the Rubraca accelerated
approval in mCRPC. Warning and precautions include myelodysplastic
syndrome (MDS), acute myeloid leukemia (AML) and embryo-fetal
toxicity. Please see additional warnings and precautions and select
safety information below.i
“Standard treatment options for men with mCRPC have been limited
to androgen receptor-targeting therapies, taxane chemotherapy,
Radium-223 and sipuleucel-T,” said Wassim Abida, M.D., Medical
Oncologist, Memorial Sloan Kettering Cancer Center, and Principal
Investigator for the TRITON2 study. “Rubraca is the first in a
class of drugs to become newly available to patients with mCRPC who
harbor a deleterious BRCA mutation. Given the level and duration of
responses observed with Rubraca in men with mCRPC and these
mutations, it represents an important and timely new treatment
option for this patient population.”
The FDA approval for this third indication for Rubraca is based
on efficacy data from patients with mCRPC and a deleterious BRCA
mutation (germline and/or somatic) enrolled in the multi-center,
single arm TRITON2 (NCT02952534) clinical trial. The major efficacy
outcomes are confirmed ORR and DOR by modified RECIST version
1.1/PCWG3 criteria assessed by blinded independent radiologic
review (IRR). Confirmed prostate-specific antigen (PSA) response
rate is an additional prespecified endpoint.i,ii
Evaluable patient populations in the supplemental New Drug
Application dataset included the following: 62 RECIST-evaluable
patients with a BRCA (germline and/or somatic) mutation and
measurable disease (IRR); 115 patients with a BRCA (germline and/or
somatic) mutation and measurable or non-measurable disease; and 209
patients with HRD-positive mCRPC enrolled in TRITON2. Patients
should be selected for treatment of mCRPC with Rubraca based on the
presence of a deleterious BRCA mutation (germline and/or
somatic).i
Efficacy outcomes and safety results are summarized belowi:
- 44% ORR (N=62; 95% CI 31, 57) by blinded-IRR assessment.
- Objective response rates were similar for patients with a
germline BRCA versus somatic BRCA mutation.
- Median DOR by blinded-IRR assessment was not evaluable (NE) at
data cut-off.
Rubraca
(N=62)
Confirmed Objective Response Rate (95%
CI)a
44% (31, 57)
Median DOR in months (95% CI)b
NE (6.4, NE)
NE = not evaluable
aDefined per modified RECIST v1.1 criteria
and with no confirmed bone progression per PCWG3.
bThe range for the DOR was 1.7-24+ months.
Fifteen of the 27 (56%) patients with a confirmed objective
response had a DOR of ≥ 6 months.
Additionally, a 55% confirmed prostate specific antigen (PSA)
response rate (95% CI 45, 64) was observed in an analysis of 115
patients with a deleterious BRCA mutation (germline and/or somatic)
and measurable or non-measurable disease.ii
The safety evaluation of Rubraca 600 mg twice daily as
monotherapy treatment is based on an analysis of 209 patients with
HRD-positive mCRPC from the multi-center, single arm TRITON2
clinical study, including 115 with BRCA-mutated mCRPC. The most
common adverse reactions (greater than or equal to 20% of patients;
CTCAE Grade 1-4) occurring in the BRCA mutant population (n=115)
were asthenia/fatigue, nausea, anemia, ALT/AST increased, decreased
appetite, constipation, rash, thrombocytopenia, vomiting, and
diarrhea. The most common laboratory abnormalities (greater than or
equal to 35% of patients; CTCAE Grade 1-4) were increase in ALT,
decrease in leukocytes, decrease in phosphate, decrease in absolute
neutrophil count, decrease in hemoglobin, increase in alkaline
phosphatase, increase in creatinine, increase in triglycerides,
decrease in lymphocytes, decrease in platelets, and decrease in
sodium.i
“The data from the TRITON2 clinical trial supporting the FDA
approval of Rubraca in mCRPC have been highly consistent over time,
and we are pleased that the FDA has granted an accelerated approval
for Rubraca in this third indication,” said Patrick J. Mahaffy,
President and CEO of Clovis Oncology. “We are proud to offer
Rubraca as a new treatment option to physicians and eligible
prostate cancer patients with a deleterious BRCA mutation beginning
today.”
“The FDA approval of Rubraca is a significant milestone for
patients with metastatic castration-resistant prostate cancer and a
deleterious BRCA mutation,” said Howard Soule, Ph.D., Executive
Vice President and Chief Science Officer of the Prostate Cancer
Foundation. “Although new treatments for prostate cancer have been
approved in recent years, most men living with advanced stages of
this disease continue to face a difficult journey with few
treatment options.”
About Prostate Cancer
The American Cancer Society estimates that nearly 192,000 men in
the United States will be diagnosed with prostate cancer in
2020iii, and the GLOBOCAN Cancer Fact Sheets estimated that
approximately 450,000 men in Europe were diagnosed with prostate
cancer in 2018.iv Castration-resistant prostate cancer has a high
likelihood of developing metastases. Metastatic
castration-resistant prostate cancer, or mCRPC, is an incurable
disease, usually associated with poor prognosis. Approximately
43,000 men in the U.S. are expected to be diagnosed with mCRPC in
2020.v According to the American Cancer Society, the five-year
survival rate for mCRPC is approximately 30 percent.vi
Approximately 12 percent of patients with mCRPC harbor a
deleterious germline and/or somatic mutation in the genes BRCA1 and
BRCA2. These molecular markers may be used to select patients for
treatment with a PARP inhibitor.vii
Rubraca U.S. FDA Approved Indication
Rubraca is indicated for the treatment of adult patients with a
deleterious BRCA mutation (germline and/or somatic)-associated
metastatic castration-resistant prostate cancer (mCRPC) who have
been treated with androgen receptor-directed therapy and a
taxane-based chemotherapy.
This indication is approved under accelerated approval based on
objective response rate and duration of response. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in confirmatory trials.
Select Important Safety Information
Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) has
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. In
TRITON2, MDS/AML was not observed in patients with mCRPC (n=209)
regardless of homologous recombination deficiency (HRD)
mutation.
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 findings in genetic toxicity and animal reproduction
studies, advise male patients with female partners of reproductive
potential or who are pregnant to use effective methods of
contraception during treatment and for 3 months following last dose
of Rubraca. Advise male patients not to donate sperm during therapy
and for 3 months following the last dose of Rubraca.
Most common adverse reactions in TRITON2 (≥ 20%; Grade 1-4) were
fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT
elevation (33%), decreased appetite (28%), rash (27%), constipation
(27%), thrombocytopenia (25%), vomiting (22%), and diarrhea
(20%).
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.
Click here for full Prescribing Information for
Rubraca.
You may also report side effects to Clovis Oncology, Inc. at
1-415-409-7220 (US toll) or 1-844-CLVS-ONC (1-844-258-7662; US
toll-free).
About Accessing Rubraca
Rubraca is available in the United States through specialty
pharmacies and distributors. Clovis is committed to ensuring
Rubraca access for patients and offers eligible patients financial
and reimbursement support through Rubraca Connections. More
information about Rubraca Connections is available at
RubracaConnections.com or by calling 1-844-779-7707 between 8 a.m.
and 8 p.m. Eastern Time, Monday through Friday.
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.
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.
This press release contains forward-looking statements (as
defined under the Private Securities Litigation Reform Act of 1995)
about the potential of Rubraca® (rucaparib) for the treatment of
adult patients with deleterious BRCA mutation (germline and/or
somatic)-associated metastatic castration-resistant prostate cancer
(mCRPC) who have been treated with androgen receptor-directed
therapy and a taxane-based chemotherapy, and reflects Clovis
Oncology’s current beliefs. As with any pharmaceutical product,
there are substantial risks and uncertainties in the process of
development and commercialization that could cause actual results
to differ materially from those expressed or implied by the
forward-looking statements. In particular, there are no guarantees
that future study results and patient experience will be consistent
with the study findings to date, that Rubraca will receive
regulatory approval for any future indications, or that it will
prove to be commercially successful. 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. All
forward-looking statements are based on information currently
available to the company, and Clovis Oncology does not undertake to
update or revise any forward-looking statements
__________________
i
Rubraca [package insert]. Boulder, CO;
Clovis Oncology. 2020
ii
Data on file. Clovis Oncology; Boulder,
CO
iii
American Cancer Society. Key Statistics
for Prostate Cancer.
https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html.
Accessed January 30, 2020.
iv
GLOBOCAN Cancer Fact Sheets: prostate
cancer. Prostate Cancer Estimated Incidence, Mortality and
Prevalence Worldwide in 2018.
https://gco.iarc.fr/today/data/factsheets/cancers/27-Prostate-fact-sheet.pdf.
Accessed February 4, 2020.
v
Cameron A. Wade and Natasha Kyprianou.
Profiling Prostate Cancer Therapeutic Resistance. International
Journal of Molecular Sciences. 2018, 19, 204.
https://www.mdpi.com/1422-0067/19/3/904/pdf.
vi
American Cancer Society. Survival rates
for prostate cancer.
https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/survival-rates.html.
Accessed February 4, 2020.
vii
Abida W, Armenia J, Gopalan A, et al.
Prospective Genomic Profiling of Prostate Cancer Across Disease
States Reveals Germline and Somatic Alterations That May Affect
Clinical Decision Making. JCO Precis Oncol 2017: 1-16.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20200515005527/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
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