AstraZeneca's Next-Generation PARP1 Inhibitor Saruparib Shows ~50% Tumor Shrinkage in Advanced HRR-Deficient Breast Cancer

Apr 09, 2024 07:31 CST Updated 07:31

AstraZeneca

Biopharmaceutical Manufacturer

▎WuXiEdited by Kant Content Team

Today, researchers announced the latest clinical trial results of AstraZeneca's next-generation PARP1 inhibitor, saruparib, at the American Association for Cancer Research (AACR) conference. The interim data analysis shows,Saruparib Shows Positive Objective Response Rate and Progression-Free Survival in Patients with Homologous Recombination Repair (HRR)-Deficient Advanced Breast Cancer, with Nearly Half of Patients Achieving Relief.

Although blocking the PARP1 enzyme may be sufficient to prevent DNA repair in HRR-deficient tumors, the United StatesAll PARP inhibitors currently approved by the FDA block both PARP1 and PARP2, and the potential toxic side effects limit their use. Saruparib is a PARP1-specific inhibitor. Since saruparib does not inhibit the activity of PARP2, its toxicity is lower than that of other PARP inhibitors, allowing it to be administered at higher doses.

PETRA is a multi-center Phase 1/2 clinical trial evaluating the safety, tolerability, and efficacy of saruparib in 306 patients with previously treated HRD-positive breast, ovarian, pancreatic, or prostate cancer. The patients’ tumors harbor mutations in HRR-related genes, including:BRCA1、BRCA2、PALB2、RAD51COrRAD51D。

Data shows,Among 31 breast cancer patients treated with a 60-milligram dose of saruparib, the objective response rate was 48.4%, the median duration of response was 7.3 months, and the median progression-free survival was 9.1 months.

▲Saruparib Molecular Structure (Image Source: PubChem)

In terms of safety, in a cohort of 141 patients with various types of cancer who received a 60-milligram dose, 92.2% of the patients experienced adverse events, and 12.1% had serious adverse events. Adverse events related to saruparib were observed in 76.6% of the patients, with 2.1% experiencing serious adverse events associated with the drug; 3.5% of the patients discontinued treatment due to adverse events related to saruparib.Researchers said the severity of the observed adverse events was milder compared to other PARP inhibitors.

Pharmacokinetic studies showed that patients maintained high levels of blood saruparib concentration at all dose levels, higher than the concentrations observed with other PARP inhibitors in clinical trials. Analysis of biopsy-obtained tissues showedSaruparib can inhibit approximately 90% of PARP activity.

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References:

[1] Next-generation PARP Inhibitor Demonstrates Clinical Benefit in Patients with Homologous Recombination Repair-deficient Breast Cancer. Retrieved April 8, 2024, from https://www.aacr.org/about-the-aacr/newsroom/news-releases/next-generation-parp-inhibitor-demonstrates-clinical-benefit-in-patients-with-homologous-recombination-repair-deficient-breast-cancer/?utm_medium=twitter&utm_source=social&sf187595659=1

[2] AstraZeneca eyes a safer PARP inhibitor, with nearly 50% response in advanced breast cancer patients: #AACR24. Retrieved April 8, 2024, from https://endpts.com/astrazeneca-eyes-a-safer-parp-inhibitor-with-nearly-50-response-in-advanced-breast-cancer-patients-aacr24/

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