AZD9750 / AstraZeneca - LARVOL DELTA

Discovery of AZD9750, an Orally Bioavailable Androgen Receptor Degrader for the Treatment of Prostate Cancer. (PubMed, J Med Chem) - "This compound inhibited AR signaling in vitro and was able to inhibit tumor growth in vivo in a mouse prostate cancer xenograft model. Extensive profiling in terms of drug-like properties allowed this to be progressed into development as AZD9750."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation • AR

ANDROMEDA: A Trial to Learn How Safe AZD9750 is and How Well it Works in People With Metastatic Prostate Cancer When Given With or Without Other Anticancer Drugs (clinicaltrials.gov) - P1/2 | N=300 | Not yet recruiting | Sponsor: AstraZeneca

First-in-human • Monotherapy • New P1/2 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Preclinical mechanistic PK/PD-efficacy modeling for AZD9750, a novel oral androgen receptor degrader (PROTAC), to support dose selection during early clinical development (AACR 2025) - "This study provides quantitative mechanistic insights into the links between compound exposure, biomarker modulation (AR) and anti-tumor responses, supporting our understanding of the required target modulation needed for maximal anti-tumor effects in these two hormone sensitive patient-derived tumor models. This mechanistic understanding is valuable to contextualize compound-induced PD modulation in patients, for given doses and schedules."

PK/PD data • Preclinical • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • AR

AZD9750, a novel androgen receptor proteolysis targeting chimera (AR-PROTAC) for the treatment of prostate cancer (AACR 2025) - "Several androgen receptor pathway inhibitors (ARPIs) have been developed and approved for the treatment of locally advanced and metastatic prostate cancer, including the androgen synthesis inhibitor, abiraterone and the AR antagonists, enzalutamide, apalutamide and darolutamide. These data confirm that AZD9750 is a potent oral degrader of AR that leads to anti-tumor efficacy in a range of hormone-sensitive and castrate-resistant PDX models. Through degradation of AR, including mutant and amplified forms of the receptor, it has the potential to overcome key resistance mechanisms arising to current standard of care therapies and provide benefit to patients with prostate cancer."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CRBN