This phase 2 study will investigate the safety and effectiveness of AZD4635 in the treatment of metastatic castration-resistant prostate cancer (mCRPC).
The main outcome will be the objective response rate (ORR) and prostate-specific antigen (PSA; a marker of prostate cancer) response. This trial is recruiting in multiple locations in the US.
Metastatic castration-resistant prostate cancer (mCRPC) is difficult to treat. It means that the cancer has spread to distant organs and no longer responds to hormonal therapy. Immunotherapy drugs are a promising strategy for advanced cancer. This treatment target specific proteins or receptors to stop cancer cells from evading the immune system. AZD4635 is an experimental immunotherapy. It targets adenosine A2A receptors on immune T cells. This prevents cancer cells from interacting and suppressing T cell responses with adenosine. Other immunotherapy drugs include oleclumab (MEDI9447) and durvalumab (Imfinzi).
This study will investigate the safety and effectiveness of AZD4635 in the treatment of mCRPC. The main outcome will be the ORR and PSA response.
Who are they looking for?
This trial will recruit 60 patients with mCRPC. All patients must provide a tumor sample. All patients must use acceptable methods of contraception during and up to 3 months after the study is completed. Patients must have received at least 2 treatment options for mCRPC. Patients must have a bodyweight of more than 35kg and be able to swallow and retain medications.
Patients are excluded from the trial if they have nausea, vomiting or gastrointestinal disease that may prevent the absorption of the medication. Patients with untreated brain tumors are excluded from the trial. Prior treatment with some immunotherapy drugs including PD-1 and PD-L1 inhibitors are excluded. Patients who have unresolved side effects from previous treatments, who had major surgery in the previous 4 weeks, who have heart conditions, kidney, liver, or bone marrow abnormalities also cannot participate. Other exclusion criteria are uncontrolled hypertension, active infections, inflammatory or immune disorders, recent chemotherapy or radiotherapy.
How will it work
Patients will be randomly assigned to treatment with AZD4635 + durvalumab (Group 1) or AZD4635 + oleclumab (Group 2). In group 1, 75 mg AZD4635 will be taken 4 times daily. Durvalumab will be administered intravenously (1500 mg) once every 4 weeks. In group 2, 50 mg AZD4635 will be taken 4 times daily. Oleclumab will be administered intravenously (1500 mg) twice weekly for 4 doses, then once every 4 weeks. Treatment will last up to 2 years.
The main outcome will be the ORR and PSA response.