Heavily-pretreated patients on lunresertib and
camonsertib combination achieved 25.9% overall response rate (ORR)
in endometrial cancer and 37.5% in platinum-resistant ovarian
cancer
Nearly half of patients with gynecologic
cancers maintained progression-free survival at 24 weeks, comparing
favorably to current standard of care
Company plans to initiate a registrational
Phase 3 trial of lunresertib in combination with camonsertib in
endometrial cancer in 2H 2025
Repare to host conference call and webcast
today at 4:30 p.m. ET to discuss these results
Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq:
RPTX), a leading clinical-stage precision oncology company, today
reported positive data from its MYTHIC Phase 1 gynecologic
expansion clinical trial evaluating the combination of lunresertib
and camonsertib (Lunre+Camo) at the recommended Phase 2 dose (RP2D)
in patients with endometrial cancer and platinum-resistant ovarian
cancer (PROC) harboring lunre-sensitizing biomarkers.
Lunresertib is a first-in-class precision oncology small
molecule PKMYT1 inhibitor which targets cell cycle regulation in
Lunre BM+ tumors (CCNE1 amplifications or FBXW7 or PPP2R1A
deleterious alterations). Camonsertib is a potential best-in-class
oral small molecule inhibitor of ATR, a critical component of the
DNA damage response pathway.
“We are encouraged by the strong response and the clear benefit
we observed in patients with endometrial and platinum-resistant
ovarian cancers in the MYTHIC clinical trial,” said Lloyd M. Segal,
President and Chief Executive Officer of Repare. “These patients
need new treatment options and our results support the potential
for Lunre+Camo to make a real, positive difference if approved,
particularly as a chemotherapy alternative. We have positive
feedback from regulatory agencies in both the US and Europe and we
look forward to getting started on a registrational Phase 3 trial
of Lunre+Camo in endometrial cancer in the second half of
2025.”
The MYTHIC clinical trial (NCT04855656) is a first-in-human,
global, open-label Phase 1 dose-escalation clinical trial to
evaluate safety, pharmacokinetics, pharmacodynamics, and
preliminary anti-tumor activity of Lunre+Camo in patients with
advanced solid tumors. As of the data cut-off date of November 14,
2024, 51 evaluable patients were enrolled in the gynecologic cancer
expansion cohort of the MYTHIC trial.
Across all tumor types treated at the optimized RP2D (n=67),
Lunre+Camo therapy demonstrated a favorable and differentiated
tolerability profile when compared to current and emerging
therapies. The most common adverse event was anemia (26.9%, Grade
3).
Key Cohort Clinical
Findings
Endometrial Cancer Patients:
The 27 evaluable patients with endometrial cancer had a median
age of 67 years. All patients exhibited high-risk profiles:
- 100% of patients have undergone prior platinum therapy
- 77.8% of patients received immune checkpoint inhibitors
- 59% of patients received the combination as a fourth line of
therapy or beyond
- 18.5% of patients had carcinosarcoma
- 85% of tumors had p53 mutations
- No tumors with microsatellite instability (MSI)-high status
were enrolled indicating proficient mismatch repair (pMMR)
status
- Within the Lunre BM+ subset: 56% of tumors had PPP2R1A
mutations; 22% carried FBXW7 mutations; 15% had CCNE1
amplification; and 7% of tumors had multiple mutations
Key efficacy outcomes in evaluable patients with endometrial
cancer (N=27):
- ORR was 25.9% (confirmed ORR in 5 out of 7 patients)
- Clinical benefit was observed in 48.1% of patients, with
responses frequently occurring after 12 weeks or more
- At the 24-week landmark analysis, nearly half of patients
experienced durable clinical benefit (24-week PFS [PFS24w] = 43%
[95% CI, 21-63%])
Platinum-Resistant Ovarian Cancer Patients:
The 24 evaluable patients with PROC had a median age of 63
years. All patients exhibited high-risk profiles:
- 100% of patients were platinum-resistant or platinum
ineligible
- 45.8% of patients had received prior PARP inhibitors
- 70.8% of patients had received prior bevacizumab
- 54% of patients received the combination as a fourth line of
therapy or beyond
- 100% of tumors had p53 mutations
- Within the Lunre BM+ subset: 87.5% of tumors had CCNE1
amplification; 4.2% had FBXW7 mutations; 4.2% had PPP2R1A
mutations; and 4.2% of tumors had multiple mutations
Key efficacy outcomes in evaluable patients with PROC
(N=24):
- ORR was 37.5% (confirmed ORR in 4 out of 9 patients)
- Clinical benefit was observed in 79% of patients
- PFS at the 24-week landmark analysis was PFS24w = 45% [95% CI,
22-66%]
“Those patients with recurrent gynecologic cancers have limited
treatment options as tumors often become resistant to standard of
care therapy,” said Brian Slomovitz, MD, MS, FACOG, Director,
Gynecologic Oncology, Co-chair of the Cancer Research Center, Mount
Sinai Medical Center. “They urgently need new treatment options.
Repare’s differentiated, biomarker-driven approach addresses this
population and may offer a solution. These data support the
potential of Lunre+Camo as a new treatment option to fill this
unmet need for patients with endometrial and platinum-resistant
ovarian cancers.”
Repare has consulted with both the U.S. Food and Drug
Administration (FDA) and the European Medicines Agency, who have
provided guidance into the Company’s registrational development
plans for Lunre+Camo in gynecologic tumors, including assessment of
the contribution of components, dose and schedule and preliminary
alignment on the proposed registrational development approach.
Repare plans to provide the final Phase 3 trial protocols for
regulatory clearance imminently and intends to start the first
Phase 3 Lunre+Camo trial in endometrial cancer in the second half
of 2025. Additionally, the Company expects to initiate a small
contribution of components trial in up to 40 patients with
endometrial cancer in the first quarter of 2025.
“The results of the MYTHIC clinical trial increase our
confidence in the potential to bring Lunre+Camo to patients living
with this aggressive subset of recurrent endometrial cancer,” said
Maria Koehler, MD, PhD, Chief Medical Officer of Repare. “We are
deeply grateful to the patients and investigators who participated
in this trial, and we look forward to building on these promising
data through the registrational clinical trials using Lunre+Camo as
a potential new standard of care for those patients, if
approved.”
Conference Call and Webcast:
Repare will host a conference call and webcast today, December
12, at 4:30 p.m. ET to discuss the results. Repare’s executive
management team will be joined by Brian Slomovitz, MD, MS, FACOG,
Director, Gynecologic Oncology, Co-chair of the Cancer Research
Center, Mount Sinai Medical Center.
To access the call, please dial (646) 357-8785 (U.S. and Canada)
or (800) 836-8184 (international) at least 10 minutes prior to the
start time and ask to be joined to the Repare Therapeutics call. A
live webcast and presentation materials will be available in the
Investor section of the Company’s website at
https://ir.reparerx.com/events-and-presentations/events. A webcast
replay will also be archived for at least 30 days.
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 Phase 1
Polθ ATPase inhibitor; 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 Company’s
future plans for clinical development of camonsertib in combination
with lunresertib (Lunre+Camo), including the Company’s plan to
initiate a registrational Phase 3 trial of Lunre+Camo in
endometrial cancer in the second half of 2025 and a contribution of
components trial in the first quarter of 2025; the tolerability,
efficacy and clinical progress of Lunre+Camo; the potential of
Lunre+Camo as a new treatment option and standard of care for
patients with endometrial and platinum-resistant ovarian cancers,
if approved; camonsertib’s potential as a best-in-class small
molecule inhibitor of ATR; and the Company’s interactions with the
FDA and the European Medicines Agency regarding registrational
development plans for Lunre+Camo. 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, fluctuations in 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
September 30, 2024 filed with the Securities and Exchange
Commission (“SEC”) and the Québec Autorité des Marchés Financiers
("AMF") on November 7, 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/.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20241212081329/en/
Investor Relations & Media Contact: Robin Garner Vice
President and Head of Investor Relations Repare Therapeutics Inc.
investor@reparerx.com
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