Repare Therapeutics Announces Phase 1 Data Highlighting Camonsertib in Combination with Radiotherapy Treatment Presented at the ASTRO Annual Meeting

Rhea-AI Summary

Repare Therapeutics (Nasdaq: RPTX) presented Phase 1 data at the ASTRO Annual Meeting, showcasing the potential of camonsertib, an oral ATR inhibitor, combined with palliative radiation for treating metastatic tumors with ATM mutations. The study enrolled 17 patients, 12 with pathogenic ATM mutations and 5 with variants of unknown significance (VUS).

Key findings include:

• Recommended Phase 2 dose: 160 mg camonsertib once-daily before 4Gy radiation on days 1-5
• At 2 months: Pathogenic group showed 2 complete responses (CR), 5 partial responses (PR), 4 stable disease (SD); VUS group had 1 PR, 4 SD
• At 6 months (9 evaluable patients): Pathogenic group reported 2 CR, 4 PR, 1 SD; VUS group had 1 SD, 1 progressive disease

The results suggest potential radiosensitization and higher clinical benefit in patients with pathogenic ATM mutations compared to those with VUS.

Positive

• Encouraging early Phase 1 data showing potential clinical benefits of camonsertib combined with palliative radiation
• Promising response rates in patients with pathogenic ATM mutations: 2 CR, 5 PR, and 4 SD at 2 months
• Potential radiosensitization effect observed in tumors with pathogenic ATM mutations
• Recommended Phase 2 dose determined for camonsertib in combination with radiation

Negative

• sample size of 17 patients in the Phase 1 trial
• Lower response rates observed in patients with ATM variants of unknown significance

Insights

Clinical Oncologist

This Phase 1 study provides promising early data on combining camonsertib with radiation therapy in patients with ATM-mutated metastatic tumors. The key findings are encouraging:

• Higher response rates in patients with pathogenic ATM mutations compared to variants of unknown significance (VUS)
• At 2 months, 58% objective response rate (2 CR + 5 PR out of 12) in the pathogenic group vs 20% (1 PR out of 5) in the VUS group
• Durable responses at 6 months in the pathogenic group with 6 out of 7 patients maintaining responses
• Recommended Phase 2 dose established at 160 mg daily

The data suggest camonsertib may enhance radiosensitivity in ATM-mutated tumors, potentially expanding treatment options for these patients. However, larger studies are needed to confirm efficacy and safety. The pan-cancer approach is notable, covering multiple tumor types including hard-to-treat cancers like pancreatic. This early signal of activity warrants further investigation in larger trials.

Biotech Investment Analyst

From an investment perspective, these early results are promising for Repare Therapeutics:

• Demonstrates potential for camonsertib in combination therapy, expanding its market opportunity
• Validates the company's precision oncology approach targeting specific genetic mutations
• Shows activity across multiple cancer types, indicating a potentially broad addressable market
• Establishes a recommended Phase 2 dose, de-risking further development

However, investors should note:

• This is still early Phase 1 data with a small sample size
• Larger studies are needed to confirm efficacy and safety
• Competition in the ATR inhibitor space from larger pharma companies

Overall, this data supports Repare's clinical development strategy and could drive increased interest from potential partners or acquirers. The stock may see a positive reaction, but sustained value creation will depend on continued clinical success and eventual commercialization.

CAMBRIDGE, Mass. & MONTREAL--(BUSINESS WIRE)-- Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq: RPTX), a leading clinical-stage precision oncology company, today reported data highlighting the clinical benefits of camonsertib, a potential best-in-class oral small molecule ATR inhibitor, combined with palliative radiation for the treatment of metastatic tumors harboring an ataxia-telangiectasia-mutated (ATM) mutation.

These data from a clinical trial conducted in collaboration with investigators at Memorial-Sloan Kettering Cancer Center were presented at the American Society for Radiation Oncology (ASTRO) annual meeting in Washington, DC by Nancy Lee, MD, FASTRO, Radiation Oncologist & Early Drug Development Specialist, Memorial Sloan Kettering Cancer Center and titled, “Genotypically-Selected Pan Cancer Trial of Camonsertib with Palliative Radiation in the Treatment of Metastatic Tumors Harboring an Ataxia-Telangiectasia Mutated (ATM) Mutation.”

“These encouraging early Phase 1 data build further support for the broad clinical potential of camonsertib,” said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. “This first-in-human study combining camonsertib, an ATR inhibitor, with palliative radiation provides early clinical data showing that the combination has the potential to radiosensitize for higher clinical benefit in patients with tumors harboring pathogenic ATM mutations versus those with variants of unknown significance. We are highly encouraged by this early look at the response rate and safety profile of this combination in the Phase 1 setting.”

Key Study Findings

• Seventeen (17) patients with metastatic tumors harboring ATM mutations were enrolled in the trial; of which 12 had pathogenic ATM mutations and 5 had ATM mutations with variants of unknown significance (VUS).
• Primary cancer histology included gastrointestinal (n=5), pancreas (n=5), breast (n=2), lung (n=2), bladder (n=2), and thyroid (n=1).
• The recommended phase 2 dose for camonsertib was determined to be 160 mg given once-daily prior to radiation (4Gy) on days 1-5.
• Interim response information was available for 16 patients at submission:

• At 2-months, there were 2 complete responses (CR), 5 partial responses (PR), and 4 stable disease (SD) in the pathogenic ATM mutation group versus 1 PR and 4 SD in the VUS group.
• At 6-months, in 9 evaluable patients, 2 CR, 4 PR, and 1 SD were reported in the pathogenic group versus 1 SD and 1 progressive disease (PD) in the VUS group.

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 design, progress and results of the Phase 1 clinical trial of camonsertib in combination with radiotherapy treatment for genotypically-selected cancers; and the Company’s future plans for clinical development of camonsertib; and the tolerability, efficacy and clinical progress of the Company’s product candidates, including camonsertib; and the benefits and ability to discover further targets and clinical candidates from the Company’s discovery platform. 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, 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/20240930713005/en/

Investor Relations & Media Contact:

Robin Garner

Vice President and Head of Investor Relations

Repare Therapeutics Inc.

investor@reparerx.com

Source: Repare Therapeutics Inc.

FAQ

What is the purpose of Repare Therapeutics' Phase 1 trial for camonsertib (RPTX)?

The Phase 1 trial aims to evaluate the clinical benefits of camonsertib, an ATR inhibitor, combined with palliative radiation for treating metastatic tumors with ATM mutations.

What were the key results of Repare Therapeutics' Phase 1 trial for camonsertib (RPTX)?

The trial showed promising response rates in patients with pathogenic ATM mutations, with 2 complete responses, 5 partial responses, and 4 stable disease at 2 months. The recommended Phase 2 dose was determined to be 160 mg of camonsertib once-daily before radiation.

How does camonsertib (RPTX) perform in combination with radiation therapy?

The Phase 1 data suggests that camonsertib combined with radiation therapy may have a radiosensitizing effect, potentially leading to higher clinical benefits in patients with tumors harboring pathogenic ATM mutations.

What types of cancer were included in Repare Therapeutics' Phase 1 trial for camonsertib (RPTX)?

The trial included patients with various metastatic tumors, including gastrointestinal, pancreatic, breast, lung, bladder, and thyroid cancers, all harboring ATM mutations.