Lunresertib + camonsertib combination
demonstrated clear signals of anti-tumor activity across multiple
tumor types and all selected genotypes
Overall response of 33.3% across all tumor
types and 50% RECIST response in patients with heavily pre-treated
gynecologic tumors, including endometrial, ovarian and cervical, at
the preliminary recommended phase 2 dose
Encouraging safety and tolerability profile
observed as monotherapy and in combination with camonsertib
Repare to host conference call and webcast
today at 5:30 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 initial data from Modules 1 and 2 of its ongoing
Phase 1 MYTHIC clinical trial evaluating lunresertib alone and in
combination with camonsertib, an ATR inhibitor. The data are being
presented in a plenary session titled, “New Drugs on the Horizon”
at the AACR-NCI-EORTC International Conference on Molecular Targets
and Cancer Therapeutics, being held October 11-15, 2023 in Boston,
Mass.
Lunresertib (RP-6306) is a first-in-class precision oncology
small molecule PKMYT1 inhibitor that targets CCNE1 amplification,
FBXW7 and PPP2R1A alterations in solid tumors. Lunresertib is being
evaluated alone and in combination with camonsertib (RP-3500 /
RG6526), a potent and selective oral inhibitor of ATR developed by
Repare and now partnered with Roche for development excluding the
lunresertib + camonsertib combination.
“We’re excited by these first clinical proof-of concept results
and believe that they further validate the pipeline power of our
SNIPRx discovery platform and demonstrate the potential of
lunresertib as the only clinical-stage PKMYT1 inhibitor,” said
Lloyd M. Segal, President and Chief Executive Officer of Repare.
“We saw early efficacy signals across multiple tumor types and in
each genotype selected, most notably in gynecological tumors where
the lunresertib + camonsertib combination provides a potential new
treatment option for these patients. Today is an important step
forward in Repare’s mission to deliver next-generation precision
oncology medicines to patients with genomically-defined tumor
alterations predicted by our platform to respond to our candidate
drugs.”
“The data presented today, although early, are highly promising
as lunresertib in combination with camonsertib results in clear
clinical activity across several tumor types and genotypes along
with a favorable safety and tolerability profile,” said Dr. Timothy
A. Yap, MBBS, PhD, FRCP, Professor in the Department of
Investigational Cancer Therapies (Phase 1 Program) and Vice
President, Head of Clinical Development in the Therapeutics
Discovery Division at The University of Texas MD Anderson Cancer
Center and Principal Investigator on the MYTHIC trial. “These early
data suggest treatment with lunresertib in combination with
camonsertib could result in efficacy outcomes for patients in the
gynecological cancer setting, an area where we’re still seeing
unmet patient needs despite current therapies.”
Key Initial Findings from the Phase 1 MYTHIC Clinical
Trial:
MYTHIC (NCT: NCT04855656), a first-in-human, global, open-label
Phase 1 dose-escalation clinical trial to evaluate safety,
pharmacokinetics, pharmacodynamics and preliminary anti-tumor
activity of lunresertib as a monotherapy (Module 1) or in
combination with camonsertib (Module 2) in patients with advanced
solid tumors harboring CCNE1 amplification or FBXW7 or PPP2R1A
deleterious alterations achieved clinical proof of concept. As of
September 5, 2023, the cutoff date for the data presented at the
AACR-NCI-EORTC conference, 67 patients were enrolled in Module 1
and 59 patients in Module 2.
- Protocol-defined overall response (OR) (RECIST or GCIG CA-125
responses) at the combination preliminary recommended phase 2 dose
(RP2D) was 33.3% (N=18); CBR at the combination preliminary RP2D
(overall response or stable disease of at least 16 weeks without
tumor progression) was 50.0%. In all evaluable patients, across all
doses (N-55), OR was 23.6% and CBR was 41.8%.
- In patients with gynecologic tumors at the combination
preliminary RP2D (N=10), the RECIST response was 50%, OR 60%, and
CBR 70%. Patients in this cohort had a median of 3 and up to 9
prior lines of therapy.
- RECIST responses in this ongoing combination trial included 8
confirmed and 3 unconfirmed partial responses (PR). Additionally, 3
patients with ovarian tumors had cancer antigen 125 (CA-125)
responses.
- RECIST responses and clinical benefit with combination therapy
was seen across all 3 lunresertib-sensitizing alterations: CCNE1
amplification or FBXW7 or PPP2R1A deleterious alterations.
Molecular response rate (MRR) was significantly higher in
combination compared to monotherapy (p=0.003), providing further
evidence of enhanced anti-tumor activity: observed MRR in
combination therapy was 50% (n=24), compared to 10% (n=30) with
lunresertib monotherapy.
- Encouraging and highly manageable safety and tolerability was
observed for the combination therapy (n=59). The most common
treatment-related adverse event (TRAE) was anemia, with grade 3
occurring in 42% of patients:
- Anemia usually improved with a one-week treatment interruption
and standard supportive care and did not lead to any therapy
discontinuations at preliminary RP2D.
- There were no Grade 4 or Grade 5 TRAEs reported at preliminary
RP2D.
- Data clearly indicates that anemia management can be
individualized and alleviated with simple patient monitoring. This
approach is now being tested in the MYTHIC trial.
- 35% of patients did not develop anemia at preliminary RP2D.
Generally, those with grade 3 anemia had the lowest hemoglobin
values at entry, were intensely pretreated with >4 prior
therapies and were of advanced age.
- Achieved the first clinical proof-of-concept for a synthetic
lethal strategy with a PKMYT1 inhibitor combined with an ATR
inhibitor in patients with molecularly-selected cancers.
- Patient enrollment in MYTHIC continues both to optimize the
schedule for the combination and to further investigate the
promising antitumor signals seen to date in a larger number of
patients with selected tumors and genomic alterations.
“The encouraging Phase 1 safety and tolerability profile and
early antitumor efficacy data provide proof of concept for
lunresertib and clear direction for further development of the
chemotherapy-free combination of lunresertib + camonsertib to
selectively target the lunresertib-relevant alterations across
multiple tumor types, including line of sight on later stage
randomized or otherwise definitive studies as the data continue to
mature,” said Maria Koehler, MD, PhD, Chief Medical Officer of
Repare. “This novel, orally delivered combination may provide new
therapeutic options in areas of high unmet need, and we look
forward to completing the multiple expansions of the Phase 1 MYTHIC
study and reporting results in 2024 with later-stage trials
expected to initiate shortly thereafter.”
Company Virtual Webcast Event:
Repare will host a conference call and webcast today, October
13, 2023, at 5:30 p.m. Eastern Time to discuss the results
presented at the AACR-NCI-EORTC conference, including updated data
since the September 5, 2023 data cutoff. Repare’s executive
management team will be joined by Dr. Timothy A. Yap, MBBS, PhD,
FRCP, Principal Investigator, Professor in the Department of
Investigational Cancer Therapies (Phase 1 Program) and Vice
President, Head of Clinical Development in the Therapeutics
Discovery Division at the University of Texas MD Anderson Cancer
Center in Houston, Texas.
To access the call, please dial (877) 870-4263 (U.S. and Canada)
or (412) 317-0790 (international) at least 10 minutes prior to the
start time and ask to be joined to the Repare Therapeutics call. A
live webcast 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’ SNIPRx® Platform
Repare’s SNIPRx® platform is a genome-wide CRISPR-based
screening approach that utilizes proprietary isogenic cell lines to
identify novel and known synthetic lethal gene pairs and the
corresponding patients who are most likely to benefit from the
Company’s therapies based on the genetic profile of their tumors.
Repare’s platform enables the development of precision therapeutics
in patients whose tumors contain one or more genomic alterations
identified by SNIPRx® screening, in order to selectively target
those tumors in patients most likely to achieve clinical benefit
from resulting product candidates.
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 clinical
development; camonsertib (also known as RP-3500 or RG6526), a
potential leading ATR inhibitor currently in Phase 1/2 clinical
development and partnered with Roche; RP-3467, a preclinical Polθ
inhibitor program; as well as several additional, undisclosed
preclinical programs, including RP-1664. For more information,
please visit reparerx.com and follow @Reparerx on X (formerly
Twitter) and LinkedIn.
SNIPRx® is a registered trademark of Repare Therapeutics
Inc.
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 safety,
efficacy and clinical progress of the Company’s clinical programs,
including lunresertib and camonsertib; and proposed further
development of the combination therapy of lunresertib and
camonsertib. 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: 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
COVID-19 pandemic, the conflict in Ukraine, rising 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; 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 Annual Report on
Form 10-K for the year ended December 31, 2022 filed with the
Securities and Exchange Commission (“SEC”) and the Québec Autorité
des Marchés Financiers ("AMF") on February 28, 2023, and its other
documents subsequently filed with or furnished to the SEC and AMF
including the Company’s Quarterly Report on Form 10-Q for the
quarter ended June 30, 2023 filed with the SEC on August 9, 2023.
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 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/20231013197907/en/
Repare Contact: Steve Forte Executive Vice-President and
Chief Financial Officer Repare Therapeutics Inc.
investor@reparerx.com
Investors: Matthew DeYoung Argot Partners
repare@argotpartners.com
Media: David Rosen Argot Partners
david.rosen@argotpartners.com 212-600-1902
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