ANDROMEDA: AZD9750 in metastatic prostate cancer

In this video, Prof Dr Emmanuel Seront, a medical oncologist at Cliniques Universitaires Saint-Luc, discusses the ANDROMEDA study, an ongoing first-in-human phase I/II trial evaluating AZD9750 in patients with metastatic castration-resistant prostate cancer.¹

AZD9750 is a novel oral androgen receptor PROTAC designed to degrade wild-type, amplified and mutant forms of the androgen receptor. This approach aims to address mechanisms of resistance to current androgen receptor pathway inhibitors, including reactivation of androgen receptor signalling through amplification or ligand-binding domain mutations.

ANDROMEDA has a modular design. One module evaluates AZD9750 as monotherapy, while another explores AZD9750 in combination with saruparib, a PARP inhibitor, in patients with homologous recombination repair alterations. Each module includes dose escalation or dose finding, followed by dose optimisation and expansion.

The main objectives are to assess safety, tolerability, dose-limiting toxicities, pharmacokinetics and preliminary antitumour activity, including PSA responses, objective response rate and progression-free survival. Although not yet practice-changing, ANDROMEDA reflects a broader therapeutic strategy in prostate cancer: moving beyond androgen receptor inhibition towards direct androgen receptor degradation.