Data presented at AACR’s Ovarian Cancer
Research Symposium confirm that ovarian and endometrial cancers
with CCNE1 amplifications, FBXW7 or PP2R1A mutations carry poor
prognosis
Significant survival disparities were
identified in patients harboring lunresertib- and
camonsertib-sensitizing biomarkers, including CCNE1 amplifications
or mutations in FBXW7 or PPP2R1A
Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq:
RPTX), a leading clinical-stage precision oncology company,
presented new data on Friday highlighting the impact of alterations
in FBXW7, PPP2R1A and CCNE1 in patients with metastatic ovarian and
endometrial cancers based on an analysis in approximately 2,000
patients from Cancer Genome Atlas Research Network and Memorial
Sloan Kettering’s Metastatic Events and Tropisms.
The poster presentation was shared at the American Association
of Cancer Research’s (AACR) 15th Annual Ovarian Cancer Research
Symposium in Seattle, underscores inherent chemotherapy resistance
and the lack of treatment options for metastatic gynecologic cancer
patients with these biomarkers.
“Patients with recurrent ovarian and endometrial cancers are
already at a disadvantage when it comes to treatment options,” said
Maria Koehler, MD, PhD, Executive Vice President and Chief Medical
Officer of Repare. “These new data highlight the urgent need for
innovative therapeutic approaches to address the specifically poor
prognosis associated with FBXW7, PPP2R1A and CCNE1 alterations
treated with standard of care-based chemotherapy. We look forward
to reporting data from our MYTHIC dose expansion trial evaluating
lunresertib in combination with camonsertib in patients with
ovarian and endometrial cancers with these biomarkers in the fourth
quarter of 2024.”
Repare Therapeutics’ Phase 1 MYTHIC clinical trial (NCT04855656)
is studying the combination of lunresertib, a first-in-class oral
small molecule PKMYT1 inhibitor, and camonsertib, a potential
best-in-class oral small molecule ATR inhibitor, in patients
harboring lunresertib-sensitizing biomarkers (Lunre BM), including
CCNE1 amplifications or mutations in FBXW7 or PPP2R1A. While CCNE1
amplifications occur in approximately 30% of platinum-resistant
ovarian cancers,1-2 and are well established as a poor prognostic
indicator in ovarian cancer,3-6 little is known about other Lunre
BM in ovarian and endometrial cancers.
Ovarian Cancer:
The presence of Lunre BM (alterations in CCNE1, PPP2R1A, or
FBXW7) in ovarian cancer patients (n=1,029) is linked to a
substantially lower survival rate compared to those without these
biomarkers, underscoring their prognostic significance:
- Median overall survival (mOS) for patients with these
biomarkers (Lunre BM+) is 26 months (95% CI, 18-38), compared to 36
months (95% CI, 30-43) for patients without these biomarkers (Lunre
BM-; HR = 1.46 [95% CI, 1.14-1.87], p=0.003), a 28% decrease in
mOS
Endometrial Cancer:
Endometrial cancer patients (n=895) with biomarkers CCNE1,
PPP2R1A, and FBXW7 demonstrate poorer survival outcomes, which are
influenced by their association with high-risk histologies and
genetic alterations:
- Median overall survival (mOS) for patients with these
biomarkers (Lunre BM+) is 30 months (95% CI, 24-38), compared to 41
months (95% CI, 31-60) for patients without these biomarkers (Lunre
BM-; HR = 1.29 [95% CI, 1.03-1.60], p=0.024), a 27% decrease in
mOS
- The presence of these biomarkers also correlates with high-risk
histologies (uterine carcinosarcoma and uterine serous carcinoma)
and p53 mutant genotypes, well known for adverse prognosis
About Repare Therapeutics Inc.
Repare Therapeutics is a leading clinical-stage precision
oncology company enabled by its proprietary synthetic lethality
approach to the discovery and development of novel therapeutics.
The Company utilizes its genome-wide, CRISPR-enabled SNIPRx®
platform to systematically discover and develop highly targeted
cancer therapies focused on genomic instability, including DNA
damage repair. The Company’s pipeline includes lunresertib (also
known as RP-6306), a PKMYT1 inhibitor currently in Phase 1/2
clinical development; camonsertib (also known as RP-3500), a
potential leading ATR inhibitor currently in Phase 1/2 clinical
development; RP-1664, a Phase 1 PLK4 inhibitor; RP-3467, a
preclinical Polθ ATPase inhibitor program; as well as additional,
undisclosed preclinical programs. For more information, please
visit reparerx.com and follow @Reparerx on X (formerly Twitter) and
LinkedIn.
Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of 1995
and securities laws in Canada. All statements in this press release
other than statements of historical facts are “forward-looking
statements. These statements may be identified by words such as
“aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,”
“forecasts,” “goal,” “intends,” “may,” “plans,” “possible,”
“potential,” “seeks,” “will” and variations of these words or
similar expressions that are intended to identify forward-looking
statements, although not all forward-looking statements contain
these words. Forward-looking statements in this press release
include, but are not limited to, statements regarding: the impact
of alterations in FBXW7, PPP2R1A and CCNE1 in patients with
metastatic ovarian and endometrial cancers; the design, objectives,
initiation, timing, progress and results of current and future
clinical trials of the Company’s product candidates, including the
timing of data from the expansion of its Phase 1 MYTHIC trial
evaluating lunresertib alone and in combination with camonsertib;
the potential of lunresertib in combination with camonsertib in
patients harboring lunresertib-sensitizing biomarkers and the
tolerability, efficacy and clinical progress of the Company’s
product candidates. These forward-looking statements are based on
the Company’s expectations and assumptions as of the date of this
press release. Each of these forward-looking statements involves
risks and uncertainties that could cause the Company’s clinical
development programs, future results or performance to differ
materially from those expressed or implied by the forward-looking
statements. Many factors may cause differences between current
expectations and actual results, including: the potential that
success in preclinical testing and earlier clinical trials does not
ensure that later clinical trials will generate the same results or
otherwise provide adequate data to demonstrate the efficacy and
safety of a product candidate; the impacts of macroeconomic
conditions, including the conflict in Ukraine and the conflict in
the Middle East, heightened inflation and uncertain credit and
financial markets, on the Company’s business, clinical trials and
financial position; unexpected safety or efficacy data observed
during preclinical studies or clinical trials; clinical trial site
activation or enrollment rates that are lower than expected; the
Company’s ability to realize the benefits of its collaboration and
license agreements; changes in expected or existing competition;
changes in the regulatory environment; the uncertainties and timing
of the regulatory approval process; and unexpected litigation or
other disputes. Other factors that may cause the Company’s actual
results to differ from those expressed or implied in the
forward-looking statements in this press release are identified in
the section titled "Risk Factors" in the Company’s Quarterly Report
on Form 10-Q for the quarter ended June 30, 2024 filed with the
Securities and Exchange Commission (“SEC”) and the Québec Autorité
des Marchés Financiers ("AMF") on August 6, 2024. The Company
expressly disclaims any obligation to update any forward-looking
statements contained herein, whether as a result of any new
information, future events, changed circumstances or otherwise,
except as otherwise required by law. For more information, please
visit reparerx.com and follow Repare on X (formerly Twitter) at
@RepareRx and on LinkedIn at
https://www.linkedin.com/company/repare-therapeutics/.
1. Cancer Genome Atlas Research Network. Nature.
2011;474(7353):609–615
2. Smith P, et al. Nat Commun. 2023;14(1):4387
3. Chan AM, et al. J Pathol Clin Res. 2020;6(4):252–262
4. Kang E-Y, et al. Cancer. 2023;129(5):697–713
5. Nakayama N, et al. Cancer. 2010;116(11):2621–2634
6. Stronach EA, et al. Mol Cancer Res. 2018;16(7):1103–1111.
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version on businesswire.com: https://www.businesswire.com/news/home/20240923948019/en/
Investor Relations & Media Contact: Robin Garner Vice
President and Head of Investor Relations Repare Therapeutics Inc.
investor@reparerx.com
Repare Therapeutics (NASDAQ:RPTX)
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부터 10월(10) 2024 으로 11월(11) 2024
Repare Therapeutics (NASDAQ:RPTX)
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