AZD4956 / AstraZeneca - LARVOL DELTA

PARTHENON: Study of AZD4956 as Monotherapy and in Combination With Anti-Cancer Agents in Participants With Advanced/Metastatic Homologous Recombination Deficient Solid Tumours (clinicaltrials.gov) - P1/2 | N=180 | Not yet recruiting | Sponsor: AstraZeneca

Monotherapy • New P1/2 trial • Breast Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Discovery of AZD4956, a potent and selective inhibitor of DNA polymerase theta, a clinical candidate for treatment of HRR-deficient tumors in combination with saruparib (AACR 2026) - "The preclinical profile, spanning efficacy, safety, DMPK and physicochemical properties, supports clinical development of AZD4956 as a combination partner with saruparib in patients with HRR deficient cancers. Clinical evaluation of AZD4956 is ongoing in a first-in-human, open-label, multicenter, phase 1/2a study in patients with HRR deficient solid tumors (PARTHENON study) in combination with saruparib."

Clinical • Combination therapy • First-in-human • Oncology • Solid Tumor • BRCA1 • BRCA2 • HRD • POLQ

AZD4956, a potent and selective inhibitor of DNA polymerase theta, enhances the activity of DNA-damaging agents in HRR defective cellular backgrounds and improves efficacy of the new generation PARP1-selective inhibitor, saruparib (AACR 2026) - "AZD4956 also potentiates other DNA-damaging agents (e.g., cisplatin, TOP1 inhibitors) specifically in HRR-deficient lines.AZD4956 shows single-agent in vitro activity in the low-nanomolar range in cell lines with PALB2, BRCA2, and RAD51C mutations, like PARPi, but no single-agent activity in BRCA1-mutant cells. Preclinical pharmacology supports AZD4956 selectivity and its potential to amplify antitumour activity when combined with PARPi in HRR-defective cancers. AZD4956 is being evaluated in PARTHENON, a first-in-human, open-label, multicentre, phase 1/2a study of AZD4956 plus saruparib in patients with HRR-deficient solid tumours."

Clinical • First-in-human • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • HRD • PALB2 • POLQ • RAD51C • TOP1