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Shares of Repare Therapeutics RPTX gained 8% on Monday after it announced dosing the first patient in an early-stage study evaluating the combination regimen of its Polθ ATPase inhibitor, RP-3467, and AstraZeneca’s AZN Lynparza (olaparib), a leading PARP inhibitor, to treat several advanced solid tumors.
Per Repare, RP-3467 has demonstrated highly significant preclinical results where treatment with the candidate in combination with AstraZeneca’s Lynparza led to complete and durable tumor regressions with no additive toxicities. Based on such encouraging results, RPTX believes that the combination has the potential to meaningfully improve patient outcomes by mitigating PARP inhibitor resistance, which represents a substantial area of unmet medical need.
Additionally, previously reported data from Repare demonstrated the potential of RP-3467 to enhance efficacy and reduce toxicity when combined with radioligand therapy and chemotherapy-based antibody-drug conjugates. The company anticipates further exploration of these areas.
Year to date, shares of Repare have plummeted 53.6% compared with the industry’s 2% decline.
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The ongoing phase I POLAR study will evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary clinical activity of RP-3467, alone or in combination with AstraZeneca’s Lynparza, in adults with molecularly selected advanced solid tumors. The study aims to enroll around 52 patients with locally advanced or metastatic epithelial ovarian cancer, metastatic breast cancer, metastatic castration-resistant prostate cancer or pancreatic adenocarcinoma.
The primary goals are to evaluate the safety and tolerability of RP-3467, both as a monotherapy and combined with AstraZeneca’s Lynparza, and to establish a preliminary recommended phase II dose for the combination therapy.
Lynparza is currently approved for four cancer types, ovarian, breast, prostate and pancreatic. AstraZeneca is also currently evaluating the drug in an earlier-line setting for the approved cancer indications as well as some other cancer types.
Other Programs in RPTX’s Clinical-Stage Pipeline
Repare uses its genome-wide, CRISPR-enabled SNIPRx platform to discover and develop highly targeted cancer therapies that cater to genomic instability, including DNA damage repair.
Lunresertib, a PKMYT1 Inhibitor, in combination with camonsertib, an ATR inhibitor, is being evaluated in RPTX’s ongoing phase I MYTHIC Module 2 dose-expansion study for ovarian and endometrial cancer indications. Top-line data from the MYTHIC Module 2 dose expansion cohorts in approximately 20-30 patients, each with ovarian and endometrial cancer, is anticipated soon.