Study explores combination in patients with DNA
damage response alterations before prostate cancer becomes
castration resistant
Pfizer Inc. (NYSE: PFE) today announced that the first
participant has been dosed in TALAPRO-3, a global, randomized,
double-blind, placebo-controlled Phase 3 clinical trial. The study
will evaluate the efficacy and safety of talazoparib, an oral poly
(ADP-ribose) polymerase (PARP) inhibitor, in combination with
enzalutamide, an androgen receptor inhibitor, compared with placebo
plus enzalutamide in men with DNA damage response (DDR)-deficient
metastatic castration-sensitive prostate cancer (mCSPC). The first
patient was dosed at a site in Glendale, California.
“The prognosis for men with advanced prostate cancer has
significantly improved since the introduction of novel hormone
therapies, but additional therapeutic options are needed for the
approximately 25 percent of men with tumors harboring DNA damage
response (DDR) gene mutations, who may have poorer outcomes,” said
Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology,
Pfizer Global Product Development. “By combining enzalutamide,
which has a proven clinical benefit in men with metastatic
castration-sensitive prostate cancer, with talazoparib, our PARP
inhibitor that is active in DDR-mutated cancer, we may be able to
offer a new treatment option that targets the underlying genetic
mechanisms associated with DDR-mutated mCSPC.”
The TALAPRO-3 trial will enroll approximately 550 men with
DDR-deficient mCSPC across 285 clinical trial sites in 28
countries. The primary endpoint of the study is radiographic
progression-free survival (rPFS), and overall survival (OS) is a
secondary endpoint. The anticipated primary completion date is
late-2024.
“With the introduction of PARP inhibitors in the metastatic
castration-resistant prostate cancer setting, it is important to
explore how a combination approach may impact outcomes for men with
metastatic castration-sensitive disease,” said Neeraj Agarwal,
M.D., Professor of Oncology at the University of Utah School of
Medicine, Senior Director for Clinical Research Innovation at
Huntsman Cancer Institute and member of the TALAPRO-3 steering
committee. “It’s exciting to be at the forefront of landmark
studies like TALAPRO-3, which are helping to further our
understanding of how different approaches may advance care for
these men.”
More information about the TALAPRO-3 trial and participating
sites may be found at www.clinicaltrials.gov (NCT04821622).
Talazoparib is currently approved under the brand name TALZENNA®
for the treatment of adult patients with deleterious or suspected
deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally
advanced or metastatic breast cancer. Selection of patients for
therapy is based on an FDA-approved companion diagnostic for
TALZENNA. Talazoparib is not approved for the treatment of prostate
cancer. Enzalutamide is an androgen receptor inhibitor currently
approved under the brand name XTANDI® and is indicated for
the treatment of patients with castration-resistant prostate cancer
(CRPC) and mCSPC. As part of a global agreement, Pfizer and
Astellas jointly commercialize XTANDI in the United States and
Astellas has responsibility for manufacturing and all additional
regulatory filings globally, as well as commercializing XTANDI
outside the United States.
In addition to the TALAPRO-3 trial, the combination of
enzalutamide plus talazoparib is being investigated in TALAPRO-2
(NCT03395197), a two-part, Phase 3, randomized, double-blind,
placebo-controlled study in men with metastatic CRPC (with and
without DDR defects).
About TALAPRO-3 Trial
The Phase 3, randomized, double-blind, placebo-controlled,
global TALAPRO-3 trial (NCT04821622) will enroll 550 men with
DDR-deficient mCSPC across approximately 285 clinical trial sites
in 28 countries. In the study, participants will be randomly
assigned to one of the two treatment groups and receive either
talazoparib (0.50 mg once daily) in combination with enzalutamide
(160 mg once daily) or placebo capsules identical to talazoparib in
combination with enzalutamide. Men with moderate renal impairment
at screening may be enrolled and given a lower dose of either
talazoparib (0.35 mg once daily) or the placebo.
The primary endpoint of the study is radiographic
progression-free survival (rPFS), which is defined as the time from
the date of randomization to first objective evidence of
radiographic progression or death, whichever occurs first.
About Metastatic Castration-Sensitive Prostate Cancer
Prostate cancer is considered metastatic once it has spread
outside of the prostate gland to other parts of the body, such as
the lymph nodes, bones, lungs, and liver.i Men are considered
castration-sensitive if their disease still responds to medical or
surgical treatment to lower testosterone levels.ii The prevalence
of mCSPC in the U.S. in 2020 was estimated to be just over
41,000.iii Studies have shown that DDR defects are found in 23%-27%
of metastatic prostate cancers.iv,v
About talazoparib
Talazoparib is an inhibitor of PARP enzymes, which play a role
in DNA response. Preclinical studies have demonstrated that
talazoparib blocks PARP enzyme activity and traps PARP at the site
of DNA damage, leading to decreased cancer cell growth and cancer
cell death. Talazoparib is being evaluated in several ongoing
clinical trials in prostate cancer, as well as other novel
combinations with targeted therapies in various solid tumors.
About XTANDI® (enzalutamide)
XTANDI (enzalutamide) is an androgen receptor inhibitor
indicated for the treatment of patients with castration-resistant
prostate cancer (CRPC) and metastatic castration-sensitive prostate
cancer (mCSPC).
Prescribing Information for XTANDI® and TALZENNA®
Please see Full Prescribing Information for XTANDI®
(enzalutamide) at www.Xtandi.com.
Please see Full Prescribing Information for TALZENNA®
(talazoparib) at www.Talzenna.com.
About the Pfizer/Astellas Collaboration
In October 2009, Medivation, Inc., which is now part of Pfizer
(NYSE:PFE), and Astellas (TSE: 4503) entered into a global
agreement to jointly develop and commercialize enzalutamide. The
companies jointly commercialize enzalutamide in the United States
and Astellas has responsibility for manufacturing and all
additional regulatory filings globally, as well as commercializing
enzalutamide outside the United States.
About Pfizer Oncology
At Pfizer Oncology, we are committed to advancing medicines
wherever we believe we can make a meaningful difference in the
lives of people living with cancer. Today, we have an
industry-leading portfolio of 24 approved innovative cancer
medicines and biosimilars across more than 30 indications,
including breast, genitourinary, colorectal, blood and lung
cancers, as well as melanoma.
About Pfizer: Breakthroughs That Change Patients’
Lives
At Pfizer, we apply science and our global resources to bring
therapies to people that extend and significantly improve their
lives. We strive to set the standard for quality, safety and value
in the discovery, development and manufacture of health care
products, including innovative medicines and vaccines. Every day,
Pfizer colleagues work across developed and emerging markets to
advance wellness, prevention, treatments and cures that challenge
the most feared diseases of our time. Consistent with our
responsibility as one of the world's premier innovative
biopharmaceutical companies, we collaborate with health care
providers, governments and local communities to support and expand
access to reliable, affordable health care around the world. For
more than 170 years, we have worked to make a difference for all
who rely on us. We routinely post information that may be important
to investors on our website at www.Pfizer.com. In addition, to
learn more, please visit us on www.Pfizer.com and follow us on
Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us
on Facebook at Facebook.com/Pfizer.
DISCLOSURE NOTICE: The information contained in this release is
as of June 23, 2021. Pfizer assumes no obligation to update
forward-looking statements contained in this release as the result
of new information or future events or developments.
This release contains forward-looking information about
talazoparib, including its potential benefits and a potential
indication in men with DNA damage response (DDR)-deficient
metastatic castration-sensitive prostate cancer, that involves
substantial risks and uncertainties that could cause actual results
to differ materially from those expressed or implied by such
statements. Risks and uncertainties include, among other things,
the uncertainties inherent in research and development, including
the ability to meet anticipated clinical endpoints, commencement
and/or completion dates for our clinical trials, regulatory
submission dates, regulatory approval dates and/or launch dates, as
well as the possibility of unfavorable new clinical data and
further analyses of existing clinical data; the risk that clinical
trial data are subject to differing interpretations and assessments
by regulatory authorities; whether regulatory authorities will be
satisfied with the design of and results from our clinical studies;
whether and when applications for talazoparib may be filed in any
jurisdictions for the potential indication or for any other
indications; whether and when any such applications for talazoparib
that may be pending or filed may be approved by regulatory
authorities, which will depend on myriad factors, including making
a determination as to whether the product’s benefits outweigh its
known risks and determination of the product’s efficacy and, if
approved, whether talazoparib will be commercially successful;
decisions by regulatory authorities impacting labeling,
manufacturing processes, safety and/or other matters that could
affect the availability or commercial potential of talazoparib;
uncertainties regarding the impact of COVID-19 of our business,
operations and financial results; and competitive developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended
December 31, 2020 and in its subsequent reports on Form 10-Q,
including in the sections thereof captioned “Risk Factors” and
“Forward-Looking Information and Factors That May Affect Future
Results”, as well as in its subsequent reports on Form 8-K, all of
which are filed with the U.S. Securities and Exchange Commission
and available at www.sec.gov and www.pfizer.com.
i American Society of Clinical Oncology. ASCO Answers: Prostate
Cancer (2018).
https://www.cancer.net/sites/cancer.net/files/asco_answers_guide_prostate.pdf.
Accessed 04-05-2021. ii Cancer.net. Prostate Cancer: Types of
Treatment (03-2018).
https://www.cancer.net/cancer-types/prostate-cancer/types-treatment.
Accessed 04-05-2021. iii Supplement to: Scher HI, Solo K, Valant J,
Todd MB, Mehra M. Prevalence of prostate cancer clinical states and
mortality in the United States: estimates using a dynamic
progression model. PLoS One 2015;10(10):e0139440. iv Robinson, D.,
Van Allen, E. M., Wu, Y. M., Schultz, N., Lonigro, R. J., Mosquera,
J. M. et al. Integrative clinical genomics of advanced prostate
cancer. Cell 161, 1215–1228 (2015). v Armenia, J., Wankowicz, S. A.
M., Liu, D., Gao, J., Kundra, R., Reznik, E. et al. The long tail
of oncogenic drivers in prostate cancer. Nat. Genet. 50, 645–651
(2018).
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Media: Eamonn Nolan
+1 (212) 733-4626
Eamonn.Nolan@pfizer.com Investors: Bryan Dunn +1 (212) 733-8917
Bryan.Dunn@pfizer.com
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