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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04381832
Recruitment Status : Recruiting
First Posted : May 11, 2020
Last Update Posted : September 11, 2020
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

Brief Summary:
This is a Phase 1b/2, open-label, multicenter platform trial to evaluate the antitumor activity and safety of 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: AB928 Drug: Zimberelimab Drug: AB680 Drug: Enzalutamide Drug: Docetaxel Phase 1 Phase 2

Detailed Description:

This study has several treatment arms and each treatment arm has 2 stages. During Stage 1 - AB928 plus zimberelimab alone, AB928 plus zimberelimab with or without a standard of care treatment (enzalutamide or docetaxel), or AB928 plus AB680 with or without zimberelimab will be administered to participants with mCRPC.

During Stage 2 - Additional participants with mCRPC may receive an AB928-based combination therapy evaluated in Stage 1 or, a standard of care treatment.

A pharmacokinetic (PK) Sub-Study (AB928 plus zimberelimab) will be conducted separately.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 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 : April 2023
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Docetaxel

Arm Intervention/treatment
Experimental: Stage 1 and 2: AB928 + zimberelimab + enzalutamide
Participants will receive oral AB928 in combination with intravenous (IV) zimberelimab and standard oral enzalutamide
Drug: AB928
AB928 is an A2aR and A2bR antagonist

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: AB928 + zimberelimab + docetaxel
Participants will receive oral AB928 in combination with IV zimberelimab and standard IV docetaxel
Drug: AB928
AB928 is an A2aR and A2bR antagonist

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: AB928 + zimberelimab
Oral AB928 in combination IV zimberelimab
Drug: AB928
AB928 is an A2aR and A2bR antagonist

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

Experimental: Stage 1 and 2: AB928 + zimberelimab + AB680
Participants will receive oral AB928 in combination with IV zimberelimab and IV AB680
Drug: AB928
AB928 is an A2aR and A2bR antagonist

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

Drug: AB680
AB680 is a Cluster of Differentiation (CD)73 Inhibitor.

Experimental: Stage 1 and 2: AB928 + AB680
Participants will receive oral AB928 in combination with IV AB680
Drug: AB928
AB928 is an A2aR and A2bR antagonist

Drug: AB680
AB680 is a Cluster of Differentiation (CD)73 Inhibitor.

Experimental: Stage 1: AB928 + zimberelimab PK Sub-Study
Participants will receive oral AB928 in combination with IV zimberelimab
Drug: AB928
AB928 is an A2aR and A2bR antagonist

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




Primary Outcome Measures :
  1. Objective response rate (ORR), defined as the composite proportion of participants with a PSA and/or radiographic complete and partial response determined by the investigator according to the Prostate Cancer Working Group 3 (PCWG3) criteria [ Time Frame: From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 1 year) ]
  2. Incidence and severity of AEs and serious adverse events (SAEs) [ Time Frame: From first dose date to 90 days after the last dose (approximately 1 year) ]

Secondary Outcome Measures :
  1. Proportion of participants with a 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 [ Time Frame: From study enrollment until disease progression or loss of clinical benefit (approximately 1 year) ]
  2. Proportion of participants with 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 [ Time Frame: From study enrollment until disease progression or loss of clinical benefit (approximately 1 year) ]
  3. Percentage of Participants with measurable disease at baseline who achieved a best overall RECIST response of CR, PR, or SD [ Time Frame: From study enrollment until disease progression or loss of clinical benefit (approximately 1 year) ]
  4. Serum/ Plasma Concentration AB928, zimberelimab, and enzalutamide when administered as part of a combination regimen in Stage 1 & 2. [ Time Frame: Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treament. (approximately 1 year) ]
  5. Serum/Plasma Concentration for AB928 and zimberelimab when administered as part of a combination regimen with docetaxel in Stage 1 & 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 year) ]
  6. Serum/Plasma Concentration for AB928 and zimberelimab when administered as part of a combination regimen in Stage 1 & 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 year) ]
  7. Serum/Plasma Concentration for AB928, zimberelimab, and AB680 when administered as part of a combination regimen in Stage 1 & 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 year) ]
  8. Serum/Plasma Concentration for AB928 and AB680 when administered as part of a combination regimen in Stage 1 & 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 year) ]
  9. Percentage of participants with anti-drug antibodies to zimberelimab [ Time Frame: Recorded at baseline (enrollment), during the first 4 months of treatment, 4 additional timepoints in the first year of treament, and at end of treatment. (approximately 1 year) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 nmol/L or 50 ng/dL)
  • Measurable or non-measurable disease as per radiographic evaluation
  • Participants with measurable disease may require a fresh tumor biopsy at study entry
  • Performance status of 0 or 1
  • Life expectancy of at least 3 months
  • Adequate hematologic and end-organ function
  • 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
  • ECG (Electrocardiogram) result with QTcF ≥480 msec
  • Prior 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 oral medications
  • HIV, Hepatitis B, and C test results negative prior to first study treatment
  • 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 3 or more lines of 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

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


Contacts
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Contact: Medical Director 510-694-6200 ClinicalTrialInquiry@arcusbio.com

Locations
Show Show 22 study locations
Sponsors and Collaborators
Arcus Biosciences, Inc.
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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: September 11, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Prostatic Diseases
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action