AstraZeneca Launches Phase 3 Trial of Next-Generation PARP1 Inhibitor Saruparib (AZD5305) in China for Metastatic Castration-Sensitive Prostate Cancer

Apr 20, 2024 08:28 CST Updated 08:28

AstraZeneca

Biopharmaceutical Manufacturer

▎WuXi AppTec Content Team Report

China Drug Clinical Trial Registration and Information Disclosure Platform recently announced,AstraZeneca has launched an international multi-center (including China) Phase 3 clinical trial in China to evaluateAZD5305TreatmentMetastatic Castration-Sensitive Prostate CancerEfficacy and Safety。Public information shows that AZD5305 (saruparib) is a second-generation PARP inhibitor developed by AstraZeneca.

Screenshot source:China Drug Clinical Trial Registration and Information Disclosure Platform Official Website

PARP inhibitors are targeted therapies developed by exploiting the DNA Damage Response (DDR) defects in tumors. They selectively kill tumor cells while sparing healthy cells and have already received regulatory approval for treating various cancer types with DDR defects, including breast cancer, ovarian cancer, and prostate cancer. However,Currently approved PARP inhibitors block both PARP1 and PARP2, and the potential toxic side effects have limited their use.

Saruparib is AstraZeneca's next-generation PARP1-specific inhibitor under research,Specifically designed for PARP1.Due to its non-inhibition of PARP2 activity, this product has lower toxicity compared to other PARP inhibitors.Preclinical studies show that, compared with the first generation of PARP1/2 inhibitors,It has better tolerance, as well as binding affinity and efficacy with the target.。

At the recently concluded American Association for Cancer Research (AACR) conference this year, AstraZeneca announced the latest clinical trial results for saruparib.PETRA'sResults.PETRA is a multi-center Phase 1/2 clinical trial designed to evaluate the safety, tolerability, and efficacy of saruparib in 306 patients with previously treated HRD-positive breast cancer, ovarian cancer, pancreatic cancer, or prostate cancer. The patients’ tumors harbor mutations in HRR-related genes, includingBRCA1、BRCA2、PALB2、RAD51COrRAD51D。

Pharmacokinetic studies showed that patients maintained high blood concentrations of saruparib at all dose levels, with levels higher than those observed with other PARP inhibitors in clinical trials. Analysis of biopsy-obtained tissue revealedSaruparib can inhibit approximately 90% of PARP activity. Additionally,Researchers said the severity of observed adverse events was milder compared to other PARP inhibitors.Notably, this product has demonstrated particularly positive objective response rates and progression-free survival in treating patients with homologous recombination repair (HRR)-deficient advanced breast cancer.Nearly Half of Patients Achieve Remission。

In addition, the researchers also announced at the 2022 AACR conferenceInSaruparib inCarryBRCA1/2，PALB2OrRAD51C/DPatients with advanced breast cancer, ovarian cancer, prostate cancer, or pancreatic cancer carrying gene mutationsFirst-in-Human Clinical TrialResults. The research results show,Seven (28%) of the 25 evaluable patients achieved objective response., including patients resistant to platinum-based chemotherapy and PARP inhibitors;59%Patients had stable disease or partial response for more than 51 weeks; among the 13 patients with evaluable circulating tumor DNA (ctDNA),ctDNA levels decreased in 7 patients (54%)。

This is a randomized, two-cohort, double-blind, placebo-controlled, Phase 3 clinical study initiated by AstraZeneca in China, aiming to evaluatesaruparibNovel Hormonal Agent Selected by Co-InvestigatorTreatmentSameHomologous Recombination Repair Gene Mutation (HRRm)And non-HRRm metastatic castration-sensitive prostate cancer patientsEfficacy and safety. The key Chinese investigator of this study is Dr. Nianzeng Xing, Chief Physician at the Cancer Hospital of the Chinese Academy of Medical Sciences.

References:

[1]ChinaOfficial Website of the Drug Clinical Trial Registration and Information Disclosure Platform. Retrieved Apr 15， 2024, from http://www.chinadrugtrials.org.cn/index.html

[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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