This study will evaluate the safety and effectiveness of a combination of study drugs including zimberelimab, etrumadenant, and quemliclustat in combination with metastasis-directed irradiation in men with hormone sensitive oligometastatic prostate cancer.
The study aims to test the hypothesis that targeted inhibition of the adenosine signaling axis (quemliclustat (CD73 antagonist) + etrumadenant (A2AR/A2BR antagonist)) and immune checkpoint inhibition (zimberelimab, α-PD-1) in combination with metastasis-directed stereotactic body radiation therapy (SBRT) will improve local control, progression-free survival (PFS), and hormone therapy-free survival and mitigate immunosuppressive changes to the tumor microenvironment (TME), compared to SBRT alone.
Patient must have histologically confirmed adenocarcinoma of the prostate.
Patient's primary prostate cancer tumor treated with surgery and/or radiation (+/- ADT).
Patients must have one to three asymptomatic metastatic tumors of the bone or soft tissue that developed in the preceding 6 months that are < 5cm or < 250 cm3.
Prostate-specific antigen (PSA) > 0.5 ng/mL but < 50ng/ml
Patient may not have had prior systemic therapy, with the exception of androgen deprivation therapy (ADT) associated with treatment of the primary prostate tumor or with salvage radiation therapy. The ADT could not exceed 3-years in duration and must have occurred greater than 6 months before time of enrollment.
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
Spinal cord compression or impending spinal cord compression.
Pulmonary and/or liver metastases > 1.0cm in largest dimension.
Sequential
Quemliclustat
Drug100mg IV once every two weeks
Etrumadenant
Drug150 mg orally (PO) once a day (QD)
Zimberelimab
Drug240 mg IV once every two weeks starting within 1 week of completing metastasis-directed SBRT
Stereotactic Body Radiation Therapy
RadiationStandard of care metastasis-directed hypofractionated radiotherapy treatment starting 4 weeks (+/- 1 week) of starting Etrumadenant and Quemliclustat
Biochemical recurrence-free survival at 12-months
Biochemical recurrence is defined as a 0.2 ng/ml increase in PSA above the post-SBRT PSA nadir. Patient will be followed until biochemical recurrence, death, or end of study, whichever comes first. Patients who are alive and biochemical recurrence free will be censored at the last PSA measurement date.
Biochemical recurrence-free survival at 6-months
To estimate the proportion of men treated with quemliclustat + etrumadenant + zimberelimab + SBRT who are free from biochemical failure at 6-months.
To estimate treatment response based on CT at 6-months
Report the percentage of patients with PD, CR, PR, and SD based on CT imaging among patients treated with oligometastasis-directed SBRT + quemliclustat + etrumadenant + zimberelimab at 6-months.
To estimate treatment response based on nuclear bone scan at 6-months.
Report the percentage of patients with PD, CR, PR, and SD based on nuclear bone scan among patients treated with oligometastasis-directed SBRT + quemliclustat + etrumadenant + zimberelimab at 6-months.
To estimate treatment response based on PSMA-PET scan at 6-months.
Report the percentage of patients with PD, CR, PR, and SD based on PSMA-PET scan among patients treated with oligometastasis-directed SBRT + quemliclustat + etrumadenant + zimberelimab at 6-months.
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Catherine Spina
Lead sponsor
Columbia University
Sponsor institution
Arcus Biosciences, Inc.
Collaborator
