MD NewslineAZD4635 with Durvalumab or Oleclumab for Metastatic Castration-Resistant Prostate Cancer

Minimal Antitumor Efficacy of AZD4635 with Immunotherapy in Pre-Treated mCRPC Patients

In a recent phase 2 study published in Cancer Immunology, Immunotherapy, the combination of AZD4635 with either durvalumab or oleclumab was evaluated for its antitumor effects in patients with metastatic castration-resistant prostate cancer (mCRPC) who had undergone previous treatments. Although the regimen was found to be safe and well-tolerated, its efficacy in reducing tumor size was minimal, suggesting a limited role of adenosine 2A receptor antagonism in the current therapeutic landscape of mCRPC.

Key Points:

• Patient Demographics and Treatment Background: The study enrolled 59 participants with a median age of 72 years, heavily pretreated for mCRPC. These participants were divided into two cohorts: 30 received AZD4635 with oleclumab, and 29 with durvalumab.
• Treatment Duration and Response: The average treatment duration was slightly over three months. Only one patient in each cohort showed a confirmed response to the treatment, highlighting the limited efficacy of the regimen.
• Stability and Progression: In the cohort treated with durvalumab, seven patients achieved stable disease for at least 35 days; however, a significant number experienced disease progression. Similarly, in the oleclumab cohort, eight patients maintained stable disease for the same duration.
• PSA Response: A prostate-specific antigen (PSA) response was observed in a small subset of patients, with two in the durvalumab cohort and three in the oleclumab cohort showing reduced PSA levels.
• Survival Outcomes: The median radiological progression-free survival was 2.3 months for durvalumab and 1.5 months for oleclumab recipients, with the median overall survival of 10.7 months reported only in the durvalumab group.
• Safety and Adverse Events: Common adverse events included nausea and fatigue, with a small number of patients experiencing severe adverse events. The majority of deaths were attributed to the underlying disease rather than the treatment.

HCN Medical Memo
The phase 2 study assessing the efficacy of AZD4635 in combination with durvalumab or oleclumab for treating metastatic castration-resistant prostate cancer presents a crucial insight into the limited potential of adenosine 2A receptor antagonism in this advanced cancer stage and serves as a reminder of the challenging nature of mCRPC treatment and the critical need for innovative approaches that could provide more substantial benefits to patients.

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