Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer

NCT ID: NCT04381832

Last Updated: 2025-07-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

173 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-07

Study Completion Date

2024-08-30

Brief Summary

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This is a Phase 1b/2, open-label, multicenter platform trial to evaluate the antitumor activity and safety of etrumadenant (AB928)-based combination therapy in participants with metastatic castrate resistant prostate cancer (mCRPC).

Detailed Description

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Conditions

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Prostatic Neoplasms, Castration-Resistant Androgen-Resistant Prostatic Neoplasms Castration Resistant Prostatic Neoplasms Prostatic Cancer, Castration-Resistant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamide

Participants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist

Zimberelimab

Intervention Type DRUG

Zimberelimab is an anti-PD-1 antibody

Enzalutamide

Intervention Type DRUG

Enzalutamide is an androgen receptor inhibitor

Stage 2: enzalutamide

Participants will receive standard oral enzalutamide

Group Type ACTIVE_COMPARATOR

Enzalutamide

Intervention Type DRUG

Enzalutamide is an androgen receptor inhibitor

Stage 1 and 2: Etrumadenant + zimberelimab + docetaxel

Participants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist

Zimberelimab

Intervention Type DRUG

Zimberelimab is an anti-PD-1 antibody

Docetaxel

Intervention Type DRUG

Docetaxel is type of chemotherapy

Stage 2: docetaxel

Participants will receive standard dose of IV docetaxel

Group Type ACTIVE_COMPARATOR

Docetaxel

Intervention Type DRUG

Docetaxel is type of chemotherapy

Stage 1 and 2: Etrumadenant + zimberelimab

Oral etrumadenant in combination IV zimberelimab

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist

Zimberelimab

Intervention Type DRUG

Zimberelimab is an anti-PD-1 antibody

Stage 2: Etrumadenant + zimberelimab + quemliclustat

Participants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist

Zimberelimab

Intervention Type DRUG

Zimberelimab is an anti-PD-1 antibody

Quemliclustat

Intervention Type DRUG

Quemliclustat is a Cluster of Differentiation (CD)73 Inhibitor.

Stage 2: Etrumadenant + quemliclustat

Participants will receive oral etrumadenant in combination with IV quemliclustat

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist

Quemliclustat

Intervention Type DRUG

Quemliclustat is a Cluster of Differentiation (CD)73 Inhibitor.

Stage 1: Etrumadenant + zimberelimab PK Sub-Study

Participants will receive oral etrumadenant in combination with IV zimberelimab

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist

Zimberelimab

Intervention Type DRUG

Zimberelimab is an anti-PD-1 antibody

Stage 1 and 2: Etrumadenant + SG

Participants will receive oral etrumadenant in combination with IV SG.

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist

SG

Intervention Type DRUG

Sacituzumab govitecan is an antibody-drug conjugate

Stage 1 and 2: Etrumadenant + Zimberelimab + SG

Participants will receive oral etrumadenant in combination with IV zimberelimab and SG.

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist

Zimberelimab

Intervention Type DRUG

Zimberelimab is an anti-PD-1 antibody

SG

Intervention Type DRUG

Sacituzumab govitecan is an antibody-drug conjugate

Interventions

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Etrumadenant

Etrumadenant is an A2aR and A2bR antagonist

Intervention Type DRUG

Zimberelimab

Zimberelimab is an anti-PD-1 antibody

Intervention Type DRUG

Quemliclustat

Quemliclustat is a Cluster of Differentiation (CD)73 Inhibitor.

Intervention Type DRUG

Enzalutamide

Enzalutamide is an androgen receptor inhibitor

Intervention Type DRUG

Docetaxel

Docetaxel is type of chemotherapy

Intervention Type DRUG

SG

Sacituzumab govitecan is an antibody-drug conjugate

Intervention Type DRUG

Other Intervention Names

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AB928 AB122 AB680 Xtandi Taxotere Trodelvy

Eligibility Criteria

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Inclusion Criteria

* Male participants; age ≥ 18 years
* Metastatic castrate-resistant prostate cancer while on anti-androgen treatment with castrate levels of testosterone (≤1.7 nanomoles per liter \[nmol/L\] or 50 nanograms per deciliter \[ng/dL\])
* Measurable or non-measurable disease as per radiographic evaluation
* Participants with measurable disease may require a fresh tumor biopsy at study entry
* Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
* Life expectancy of at least 3 months
* Adequate hematologic and end-organ function
* Human immunodeficiency virus (HIV), Hepatitis B, and C test results negative prior to first study treatment


* Disease progression after prior treatment with abiraterone


* Disease progression after prior androgen synthesis inhibitor therapy


* Disease progression after prior androgen synthesis inhibitor treatment and up to 2 prior lines of taxane chemotherapy

Exclusion Criteria

* Prior treatment with immune checkpoint blockade therapy
* Prior anticancer treatment including approved agents, systemic radiotherapy, or investigational therapy, within 2-4 weeks prior first study treatment
* Corrected QT interval (QTc) ≥480 msec using Fredericia's QT correction formula (based on an average of triplicate recordings)
* Prior allogeneic stem cell or solid organ transplantation
* Prior treatment with drugs that stimulate the immune system within 4 weeks prior to first study treatment
* Prior treatment with drugs that suppress the immune system within 2 weeks prior to first study treatment
* Received a live, attenuated vaccine within 4 weeks prior to first study treatment, or may need to receive a vaccine during study treatment
* Presence of metastases in the brain or cancer spreading into the cerebrospinal fluid - CSF (leptomeningeal disease)
* Prior pulmonary fibrosis, pneumonia, or pneumonitis
* Cancer other than prostate within 2 years prior to study entry, except for some cancers with a low risk of spreading like non-melanoma skin
* Prior treatment with an agent targeting the adenosine pathway
* No oral or IV antibiotics within 2 weeks prior to first study treatment
* No severe infection within 4 weeks prior to first study treatment
* No clinically significant cardiac disease
* Inability to swallow medications


* Prior treatment with docetaxel, cabazitaxel, or other taxane chemotherapy (prior docetaxel \[up to 6 cycles\] for hormone-sensitive prostate cancer is allowed if the last dose was at least 6 months prior to study treatment initiation)
* Prior treatment with enzalutamide or similar therapy other than abiraterone
* Active or history of autoimmune disease or immune deficiency
* History of severe allergic reactions to antibody therapy
* Concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong CYP3A4 inducers and CYP3A4 inhibitors) within 4 weeks prior to and throughout study treatment


* Prior treatment with docetaxel, cabazitaxel, or other taxane chemotherapy
* Active or history of autoimmune disease or immune deficiency
* History of severe allergic reactions to antibody therapy
* Concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong CYP3A4 inducers and CYP3A4 inhibitors) within 4 weeks prior to and throughout study treatment


* Prior treatment with docetaxel, cabazitaxel, topoisomerase 1 inhibitors, or other taxane chemotherapy
* Active or history of autoimmune disease or immune deficiency
* History of severe allergic reactions to antibody therapy
* Concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong CYP3A4 inducers and CYP3A4 inhibitors) within 4 weeks prior to and throughout study treatment
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

Arcus Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Arcus Biosciences

Locations

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The Oncology Institute of Hope & Innovation

Cerritos, California, United States

Site Status

The University of California, Los Angeles

Encino, California, United States

Site Status

The University of California, Irvine Medical Center

Orange, California, United States

Site Status

Florida Cancer Specialists South

Sarasota, Florida, United States

Site Status

Florida Cancer Specialists North

St. Petersburg, Florida, United States

Site Status

Florida Cancer Specialists Panhandle

Tallahassee, Florida, United States

Site Status

Florida Cancer Specialists East

West Palm Beach, Florida, United States

Site Status

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

Affinity Health Hope & Healing Cancer Services

Hinsdale, Illinois, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

New York University, Langone Health

New York, New York, United States

Site Status

Wilmot Cancer Institute Oncology, University of Rochester

Rochester, New York, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Tennessee Oncology - Chattanooga

Chattanooga, Tennessee, United States

Site Status

Tennessee Oncology - Nashville

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Medical Oncology Associates, PS (dba Summit Cancer Centers)

Spokane, Washington, United States

Site Status

Juravinski Cancer Center

Hamilton, Ontario, Canada

Site Status

Centre hospitalier de l'Université de Montréal (CHUM) Centre de Recherche

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

Other Identifiers

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ARC-6

Identifier Type: -

Identifier Source: org_study_id

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