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Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04381832
Recruitment Status : Active, not recruiting
First Posted : May 11, 2020
Last Update Posted : February 7, 2024
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

Study Description
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Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms, Castration-Resistant Androgen-Resistant Prostatic Neoplasms Castration Resistant Prostatic Neoplasms Prostatic Cancer, Castration-Resistant Drug: Etrumadenant Drug: Zimberelimab Drug: Quemliclustat Drug: Enzalutamide Drug: Docetaxel Drug: SG Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 173 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 7, 2020
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : August 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
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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 Name: AB928

Drug: Zimberelimab
Zimberelimab is an anti-PD-1 antibody
Other Name: AB122

Drug: Enzalutamide
Enzalutamide is an androgen receptor inhibitor
Other Name: Xtandi
Active Comparator: Stage 2: enzalutamide
Participants will receive standard oral enzalutamide
 Drug: Enzalutamide
Enzalutamide is an androgen receptor inhibitor
Other Name: 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 Name: AB928

Drug: Zimberelimab
Zimberelimab is an anti-PD-1 antibody
Other Name: AB122

Drug: Docetaxel
Docetaxel is type of chemotherapy
Other Name: Taxotere
Active Comparator: Stage 2: docetaxel
Participants will receive standard dose of IV docetaxel
 Drug: Docetaxel
Docetaxel is type of chemotherapy
Other Name: Taxotere
Experimental: Stage 1 and 2: Etrumadenant + zimberelimab
Oral etrumadenant in combination IV zimberelimab
 Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist
Other Name: AB928

Drug: Zimberelimab
Zimberelimab is an anti-PD-1 antibody
Other Name: 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 Name: AB928

Drug: Zimberelimab
Zimberelimab is an anti-PD-1 antibody
Other Name: AB122

Drug: Quemliclustat
Quemliclustat is a Cluster of Differentiation (CD)73 Inhibitor.
Other Name: 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 Name: AB928

Drug: Quemliclustat
Quemliclustat is a Cluster of Differentiation (CD)73 Inhibitor.
Other Name: 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 Name: AB928

Drug: Zimberelimab
Zimberelimab is an anti-PD-1 antibody
Other Name: 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 Name: AB928

Drug: SG
Sacituzumab govitecan is an antibody-drug conjugate
Other Name: 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 Name: AB928

Drug: Zimberelimab
Zimberelimab is an anti-PD-1 antibody
Other Name: AB122

Drug: SG
Sacituzumab govitecan is an antibody-drug conjugate
Other Name: Trodelvy


Outcome Measures
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Primary Outcome Measures :
  1. Objective Response Rate (ORR) in Stage 1 and 2 [ Time Frame: From study enrolment until participant discontinuation, or first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 3-5 years) ]
    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

  2. Incidence and Severity of AEs and Serious Adverse Events (SAEs) in Stage 1 [ Time Frame: From first dose date to 90 days after the last dose (approximately 1.5 years) ]

Secondary Outcome Measures :
  1. Percentage of participants with a PSA response in Stage 1 and 2 [ Time Frame: From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years) ]
    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

  2. Percentage of participants with Radiographic Response in Stage 1 and 2 [ Time Frame: From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years) ]
    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

  3. Percentage of Participants with Disease Control Rate in Stage 1 and 2 [ Time Frame: From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years) ]
    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).

  4. Serum/Plasma Concentration for etrumadenant, zimberelimab, and enzalutamide when administered as part of a combination regimen in Stage 1 and 2. [ Time Frame: 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) ]
  5. Serum/Plasma Concentration for etrumadenant and zimberelimab when administered as part of a combination regimen with docetaxel in Stage 1 and 2 [ Time Frame: 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) ]
  6. Serum/Plasma Concentration for etrumadenant and zimberelimab when administered as part of a combination regimen in Stage 1 and 2 [ Time Frame: 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) ]
  7. Serum/Plasma Concentration for etrumadenant, zimberelimab, and AB680 when administered as part of a combination regimen in Stage 1 and 2 [ Time Frame: 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) ]
  8. Serum/Plasma Concentration for etrumadenant and AB680 when administered as part of a combination regimen in Stage 1 and 2. [ Time Frame: 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) ]
  9. Percentage of participants with anti-drug antibodies to zimberelimab in Stage 1 and 2 [ Time Frame: 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) ]
  10. Incidence and severity of AEs and serious adverse events (SAEs) in Stage 2 [ Time Frame: From first dose date to 90 days after the last dose (approximately 3-5 years) ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04381832


Locations
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Sponsors and Collaborators
Arcus Biosciences, Inc.
Gilead Sciences
Investigators
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Study Director: Medical Director Arcus Biosciences
More Information
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Responsible Party: Arcus Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT04381832    
Other Study ID Numbers: ARC-6
First Posted: May 11, 2020    Key Record Dates
Last Update Posted: February 7, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
URL: https://trials.arcusbio.com/our-transparency-policy

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Neoplasms
Prostatic Neoplasms, Castration-Resistant
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
 Male Urogenital Diseases
Docetaxel
Quemliclustat
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immune Checkpoint Inhibitors
Antineoplastic Agents, Immunological