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

NCT05915442 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AAAU4675
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Oligometastatic Prostate Cancer

Keywords

Adenosine Signaling; AB680; AB928; AB122; Quemliclustatm; Etrumadenant; Zimberelimab

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (7)

• Biochemical recurrence-free survival at 6-months

  6 months

• To estimate treatment response based on CT at 6-months

  6 months

• To estimate treatment response based on nuclear bone scan at 6-months.

  6-months

• To estimate treatment response based on PSMA-PET scan at 6-months.

  6-months

• Proportion of patients who start ADT.

  6, 12 months and 3 years.

Study Arms (1)

Treatment with quemliclustatm, etrumadenant, zimberelimab and SBRT

EXPERIMENTAL

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.

Drug: Quemliclustat; Drug: Etrumadenant; Drug: Zimberelimab; Radiation: Stereotactic Body Radiation Therapy

Interventions

Quemliclustat DRUG

100mg IV once every two weeks

Also known as: AB680

Treatment with quemliclustatm, etrumadenant, zimberelimab and SBRT

Etrumadenant DRUG

150 mg orally (PO) once a day (QD)

Also known as: AB928

Treatment with quemliclustatm, etrumadenant, zimberelimab and SBRT

Zimberelimab DRUG

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

Also known as: AB122

Treatment with quemliclustatm, etrumadenant, zimberelimab and SBRT

Stereotactic Body Radiation Therapy RADIATION

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

Also known as: SBRT

Treatment with quemliclustatm, etrumadenant, zimberelimab and SBRT

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• PSA doubling time (PSADT) \< 15 months (using all available PSA values from time of relapse)
• Testosterone \> 125 ng/mL
• Age ≥18 years.
• Patient must have life expectancy \> 12 months.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Normal organ and marrow function as defined below:
• leukocytes ≥3,000/mcL
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin within normal institutional limits
• aspartate transaminase (AST)(serum glutamic-oxaloacetic transaminase (SGOT))/alanine transaminase (ALT)(serum glutamic-pyruvic transaminase (SGPT) ) ≤2.5 × institutional upper limit of normal creatinine, within normal institutional limits

You may not qualify if:

• 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.
• History of malignancy other than prostate cancer within 2 years prior to screening, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as nonmelanoma skin carcinoma or ductal carcinoma in situ.
• Use of other investigational agents or treatment protocol.
• Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment with the exception of patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Inability to swallow medications.
• Malabsorption condition that would alter the absorption of orally administered medications.
• Grade ≥ 3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Positive total hepatitis B core antibody (HBcAb) test at screening. Patients can be eligible if positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV test will be performed only for participants who have a positive total HBcAb test. Due to safety concerns related to viral activation, development of a secondary malignancy, as well as the potential for increased treatment-related toxicity, eligible participants must not have evidence of chronic viral infection at screening.
• Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had:
• Oral treatment with strong inhibitors of breast cancer resistance protein (BCRP) (e.g., cyclosporin A, eltrombopag) or BRCP substrates with a narrow therapeutic window, administered orally (e.g., prazosin, rosuvastatin) within 4 weeks or 5 drug-elimination half-lives of the drug (whichever is longer) prior to initiation of study treatment.

Sponsors & Collaborators

• Catherine Spina: lead
• Arcus Biosciences, Inc.: collaborator

Study Sites (1)

Columbia University Irving Medical Center / NewYork-Presbyterian Hospital

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Interventions

quemliclustat; zimberelimab; Radiosurgery

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Catherine S. Spina, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine S. Spina, MD, PhD

CONTACT

212-305-7406; css2190@cumc.columbia.edu

Research Nurse Navigator

CONTACT

212-342-5162; cancerclinicaltrials@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Radiation Oncology

Model Details: 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.

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: June 23, 2023
• Study Start: July 1, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)