Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Immune System Diseases

Prostatic Neoplasms

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Antineoplastic Agents

Hormones

Adenosine

Quemliclustat

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Subjects with metastatic prostate cancer will receive quemliclustat and etrumadenant for 4 weeks prior to metastasis-directed SBRT (Stereotactic Body Radiation Therapy). Within one week of completing SBRT, subjects will also start zimberelimab.

Etrumadenant

240 mg IV once every two weeks starting within 1 week of completing metastasis-directed SBRT

Zimberelimab

Standard of care metastasis-directed hypofractionated radiotherapy treatment starting 4 weeks (+/- 1 week) of starting Etrumadenant and Quemliclustat

Stereotactic Body Radiation Therapy

Catherine S. Spina, MD, PhD

Research Nurse Navigator

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.

The optimal therapeutic approach to men with oligometastatic (1-3 or 1-5 sites of metastatic disease) prostate cancer is ever more important as advanced imaging technologies are becoming standard of care, providing clinicians with the tools to accurately diagnose and localize oligometastatic prostate cancer. Hence, methods to improve the local curative potential of stereotactic body radiation therapy (SBRT) is a timely and important opportunity. In addition, previous data suggest that the adenosine A2A pathway may be a particularly attractive avenue for intervention in the context of radiation, thus influencing multiple suppressive populations within the tumor microenvironment (TME).

Immunotherapy based on the PD-1/PD-L1 signaling axis is a mainstay of therapy across multiple types of malignancies. This study aims to evaluate the effectiveness of a PD-1 inhibitor (zimberelimab) in combination with a selective dual antagonist of A2aR and A2bR (etrumadenant) and an anti-CD73 (quemliclustat). Immune checkpoint inhibitors and targeted inhibitors of the adenosine signaling axis modulate the TME and aspects of the systemic immune system to overcome tumor-induced immune suppression and improve responses to therapy.

This study aims to determine the effect of etrumadenant, quemliclustat and zimberelimab \[experimental\] when given with ablative radiation (SBRT)\[standard of care\] on the oligoprogressive disease (hormone sensitive oligometastatic prostate cancer), defined by being free from radiographic progression of irradiated target metastases and PSA (prostate surface antigen) response at 6 months. PSA response, local control, progression-free survival (PFS), treatment response, ADT-free survival, time-to-pain, and safety and tolerability will also be measured. By employing a Simon Two-Stage design, the trial will test whether or not etrumadenant + quemliclustat and zimberelimab combined with ablative radiation (SBRT) will improve PFS compared to SBRT alone (ORIOLE).

Simon Two-Stage design: In the first stage, trial will enroll 14 patients. If two or more patients show progression at 6 months, the study is terminated at the end of stage I. However, if 13 of the 14 remain free from progressive disease at 6 months, then the study would move onto the second stage. In this stage, n=9 additional patients will be enrolled, for a total of 23 total. If 21 of the 23 patients remain progression-free at 6 months, then the null hypothesis is rejected, and we will consider the addition of quemliclustat, etrumadenant, and zimberelimab to SBRT worthy of further study.

Adenosine Signaling Modulation and Immune Checkpoint Inhibition With Hormone Sensitive Oligometastatic Prostate Cancer

Phase II Single Arm Study Testing SBRT, Adenosine Signaling Modulation (AB680, AB928), and Immune Checkpoint Inhibition (AB122) for Men With Hormone Sensitive Oligometastatic Prostate Cancer

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.

To estimate the proportion of men treated with quemliclustat + etrumadenant + zimberelimab + SBRT who are free from biochemical failure 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.

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.

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.

Quantify pain using a numeric 10-point scale using the Brief Pain Inventory (BPI) every 12 weeks from time of enrollment.

Spots Global Cancer Trial Database for ab680

Every month we try and update this database with for ab680 cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for ab680

Every month we try and update this database with for ab680 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ab680 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.