Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (ARC-6)

A Phase 1b/2, Open-Label, Randomized Platform Study Evaluating the Efficacy and Safety of AB928-Based Treatment Combinations in Patients With Metastatic Castrate Resistant Prostate Cancer

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Prostatic Neoplasms, Castration-Resistant; Prostatic Cancer, Castration-Resistant; Castration Resistant Prostatic Neoplasms; Androgen-Resistant Prostatic Neoplasms
• Intervention / Treatment: Drug: Etrumadenant; Drug: Zimberelimab; Drug: Enzalutamide; Drug: Docetaxel; Drug: Quemliclustat; Drug: SG

Detailed Description

This study has several treatment arms and each treatment arm has 2 stages. During Stage 1 - Etrumadenant plus zimberelimab (AB122) alone, etrumadenant plus zimberelimab with or without a standard of care treatment (enzalutamide or docetaxel), or etrumadenant plus AB680 with or without zimberelimab, or etrumadenant plus Sacituzumab govitecan (SG) alone or etrumadenant plus zimberelimab plus SG will be administered to participants with mCRPC.

During Stage 2 - Additional participants with mCRPC may receive an etrumadenant-based combination therapy evaluated in Stage 1 or, a standard of care treatment.

A pharmacokinetic (PK) Sub-Study (etrumadenant plus zimberelimab) will be conducted separately.

Treatment may continue until unacceptable toxicity or progressive disease, or other reasons specified in the protocol.

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Medical Director; Phone Number: +1-510-462-3330; Email: ClinicalTrials@arcusbio.com

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V5C2
      • Juravinski Cancer Center
  • Quebec
    • Montréal, Quebec, Canada, H2X 3E4
      • Centre hospitalier de l'Université de Montréal (CHUM) Centre de Recherche
• United States
  • California
    • Cerritos, California, United States, 90703
      • The Oncology Institute of Hope & Innovation
    • Encino, California, United States, 91436
      • The University of California, Los Angeles
    • Orange, California, United States, 92868
      • The University of California, Irvine Medical Center
    • San Francisco, California, United States, 94158
      • The University of California, San Francisco
  • Florida
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists NORTH
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists South
    • Tallahassee, Florida, United States, 32308
      • Florida Cancer Specialists Panhandle
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists East
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
    • Hinsdale, Illinois, United States, 60521
      • Affinity Health Hope & Healing Cancer Services
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • New York
    • New York, New York, United States, 10016
      • New York University, Langone Health
    • Rochester, New York, United States, 14642
      • Wilmot Cancer Institute Oncology, University of Rochester
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology - Chattanooga
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology - Nashville
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates, PS (dba Summit Cancer Centers)
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

General 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

Inclusion Criteria for Participants receiving an enzalutamide-containing treatment

• Disease progression after prior treatment with abiraterone

Inclusion Criteria for Participants receiving a docetaxel-containing treatment

• Disease progression after prior androgen synthesis inhibitor therapy

Inclusion Criteria for all other Participants

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

General 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

Exclusion Criteria for Participants receiving an enzalutamide-containing treatment

• 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

Exclusion Criteria for Participants receiving a docetaxel-containing 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

Exclusion Criteria for all other Participants

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamide; Participants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide	Drug: Etrumadenant; Etrumadenant is an A2aR and A2bR antagonist; Other Names: AB928; Drug: Zimberelimab; Zimberelimab is an anti-PD-1 antibody; Other Names: AB122; Drug: Enzalutamide; Enzalutamide is an androgen receptor inhibitor; Other Names: Xtandi
Active Comparator: Stage 2: enzalutamide; Participants will receive standard oral enzalutamide	Drug: Enzalutamide; Enzalutamide is an androgen receptor inhibitor; Other Names: Xtandi
Experimental: Stage 1 and 2: Etrumadenant + zimberelimab + docetaxel; Participants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel	Drug: Etrumadenant; Etrumadenant is an A2aR and A2bR antagonist; Other Names: AB928; Drug: Zimberelimab; Zimberelimab is an anti-PD-1 antibody; Other Names: AB122; Drug: Docetaxel; Docetaxel is type of chemotherapy; Other Names: Taxotere
Active Comparator: Stage 2: docetaxel; Participants will receive standard dose of IV docetaxel	Drug: Docetaxel; Docetaxel is type of chemotherapy; Other Names: Taxotere
Experimental: Stage 1 and 2: Etrumadenant + zimberelimab; Oral etrumadenant in combination IV zimberelimab	Drug: Etrumadenant; Etrumadenant is an A2aR and A2bR antagonist; Other Names: AB928; Drug: Zimberelimab; Zimberelimab is an anti-PD-1 antibody; Other Names: AB122
Experimental: Stage 2: Etrumadenant + zimberelimab + quemliclustat; Participants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat	Drug: Etrumadenant; Etrumadenant is an A2aR and A2bR antagonist; Other Names: AB928; Drug: Zimberelimab; Zimberelimab is an anti-PD-1 antibody; Other Names: AB122; Drug: Quemliclustat; Quemliclustat is a Cluster of Differentiation (CD)73 Inhibitor.; Other Names: AB680
Experimental: Stage 2: Etrumadenant + quemliclustat; Participants will receive oral etrumadenant in combination with IV quemliclustat	Drug: Etrumadenant; Etrumadenant is an A2aR and A2bR antagonist; Other Names: AB928; Drug: Quemliclustat; Quemliclustat is a Cluster of Differentiation (CD)73 Inhibitor.; Other Names: AB680
Experimental: Stage 1: Etrumadenant + zimberelimab PK Sub-Study; Participants will receive oral etrumadenant in combination with IV zimberelimab	Drug: Etrumadenant; Etrumadenant is an A2aR and A2bR antagonist; Other Names: AB928; Drug: Zimberelimab; Zimberelimab is an anti-PD-1 antibody; Other Names: AB122
Experimental: Stage 1 and 2: Etrumadenant + SG; Participants will receive oral etrumadenant in combination with IV SG.	Drug: Etrumadenant; Etrumadenant is an A2aR and A2bR antagonist; Other Names: AB928; Drug: SG; Sacituzumab govitecan is an antibody-drug conjugate; Other Names: Trodelvy
Experimental: Stage 1 and 2: Etrumadenant + Zimberelimab + SG; Participants will receive oral etrumadenant in combination with IV zimberelimab and SG.	Drug: Etrumadenant; Etrumadenant is an A2aR and A2bR antagonist; Other Names: AB928; Drug: Zimberelimab; Zimberelimab is an anti-PD-1 antibody; Other Names: AB122; Drug: SG; Sacituzumab govitecan is an antibody-drug conjugate; Other Names: Trodelvy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) in Stage 1 and 2	ORR defined as the composite proportion of participants with a Prostate Specific Antigen (PSA) and/or radiographic complete response (CR) and partial response (PR) determined by the investigator according to the Prostate Cancer Working Group 3 (PCWG3) criteria	From study enrolment until participant discontinuation, or first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 3-5 years)
Incidence and Severity of AEs and Serious Adverse Events (SAEs) in Stage 1		From first dose date to 90 days after the last dose (approximately 1.5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with a PSA response in Stage 1 and 2	PSA response defined as the proportion of participants with a confirmed PSA decrease from baseline of 50% or more based on two consecutive assessments measured 3 to 4 weeks apart	From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years)
Percentage of participants with Radiographic Response in Stage 1 and 2	Radiographic Response is measurable disease at baseline who achieved a best overall response of CR or PR according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years)
Percentage of Participants with Disease Control Rate in Stage 1 and 2	Disease Control Rate is defined as the percentage of participants with measurable disease at baseline who achieved a best overall RECIST response of CR, PR, or Stable Disease (SD).	From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years)
Serum/Plasma Concentration for etrumadenant, zimberelimab, and enzalutamide when administered as part of a combination regimen in Stage 1 and 2.		Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1.5 years)
Serum/Plasma Concentration for etrumadenant and zimberelimab when administered as part of a combination regimen with docetaxel in Stage 1 and 2		Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1.5 years)
Serum/Plasma Concentration for etrumadenant and zimberelimab when administered as part of a combination regimen in Stage 1 and 2		Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1.5 years)
Serum/Plasma Concentration for etrumadenant, zimberelimab, and AB680 when administered as part of a combination regimen in Stage 1 and 2		Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1.5 years)
Serum/Plasma Concentration for etrumadenant and AB680 when administered as part of a combination regimen in Stage 1 and 2.		Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1.5 years)
Percentage of participants with anti-drug antibodies to zimberelimab in Stage 1 and 2		Recorded at baseline (enrollment), during the first 4 months of treatment, 4 additional timepoints in the first year of treatment, and at end of treatment. (approximately 1.5 years)
Incidence and severity of AEs and serious adverse events (SAEs) in Stage 2		From first dose date to 90 days after the last dose (approximately 3-5 years)

Collaborators and Investigators

• Sponsor: Arcus Biosciences, Inc.
• Collaborators: Gilead Sciences
• Investigators: Study Director: Medical Director, Arcus Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2020
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: May 6, 2020
• First Submitted That Met QC Criteria: May 6, 2020
• First Posted (Actual): May 11, 2020

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Neoplasms; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Docetaxel; Quemliclustat
• Other Study ID Numbers: ARC-6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.

For more information, please visit our website.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No