A newly published phase 2 study finds that the antitumor effect of AZD4635 with durvalumab or oleclumab is minimal in pretreated metastatic castration-resistant prostate cancer, with the treatment regimen being well-tolerated and generally safe.
Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis and limited overall survival rates. The standard treatment for mCRPC patients comprises novel hormonal medications and taxanes. Adenosine 2A receptor (A2AR) inhibition serves as an adjunct to immune-targeting therapies. One such A2AR antagonist is AZD4635.
In this phase 2 study, the authors assessed the activity of AZD4635 combined with oleclumab or durvalumab in patients with mCRPC. The study’s findings are published in the journal Cancer Immunology, Immunotherapy.
Baseline Characteristics
The study enrolled a total of 59 patients, of whom 30 received AZD4635 with oleclumab and 29 received AZD4635 with durvalumab. The median age of the participants was 72 (53–90) years, and the majority of participants were heavily pretreated. Approximately 41% of the participants have more than two sites of metastasis.
Disease Progression
The mean treatment duration was 3.05 (0.3–1.44) months for AZD4635 with durvalumab (Module 1) and 3.22 (0.2–15.2) months for AZD4635 with oleclumab (Module 2). In Module 1, objective response was observed in one patient, seven patients had stable disease for a minimum of 35 days, ten patients had disease progression, and one patient died. In Module 2, eight patients had stable disease for a minimum of 35 days, 11 patients had disease progression, and one patient died. The remaining patients in both cohorts had Response Evaluation Criteria in Solid Tumors (RECIST) progression.
Prostate Specific Antigen Response
Two patients in Module 1 and three patients in Module 2 had a prostate-specific antigen (PSA) response to AZD4635 treatment. Only one patient from each Module 1 and Module 2 experienced a confirmed treatment response.
Patient Survival
The median radiological progression-free survival (rPFS) in Module 1 and Module 2 was 2.3 (1.6–3.8) and 1.5 (1.3–4.0) months, respectively. The median overall survival in Module 1 was 10.7 (7.2–NE) months. There were no differences in progression-free survival between participants with high or low levels of peripheral adenosine signaling.
Safety Profile
The most frequent adverse events associated with AZD4635 were nausea, fatigue, and reduced appetite in Module 1 and nausea, fatigue, and vomiting in Module 2. Three and two patients in Module 1 and Module 2, respectively, experienced a minimum of one grade ≥ 3 adverse event. In Module 1 and Module 2, 11/12 and 9/11 deaths were attributed to the disease under investigation, respectively.
Source:
Falchook, G. S., Reeves, J. A., Gandhi, S., Spigel, D. R., Arrowsmith, E., George, D. J., Karlix, J. L., Pouliot, G. P., Hattersley, M. M., Gangl, E., James, G., Thompson, J., Russell, D. L., Patel, B., Kumar, R., & Lim, E. A. (2024). A phase 2 study of AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer. Cancer Immunology, Immunotherapy, 73(4). https://doi.org/10.1007/s00262-024-03640-6
