Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (ARC-6)
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| ClinicalTrials.gov Identifier: NCT04381832 |
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Recruitment Status :
Recruiting
First Posted : May 11, 2020
Last Update Posted : January 30, 2023
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Sponsor:
Arcus Biosciences, Inc.
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Arcus Biosciences, Inc.
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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 |
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 (Clinical Trial) |
| Estimated Enrollment : | 342 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 : | December 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Prostate cancer
MedlinePlus related topics:
Prostate Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamide
Participants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide
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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 |
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Active Comparator: Stage 2: enzalutamide
Participants will receive standard oral enzalutamide
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Drug: Enzalutamide
Enzalutamide is an androgen receptor inhibitor
Other Name: Xtandi |
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Experimental: Stage 1 and 2: Etrumadenant + zimberelimab + docetaxel
Participants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel
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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 |
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Active Comparator: Stage 2: docetaxel
Participants will receive standard dose of IV docetaxel
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Drug: Docetaxel
Docetaxel is type of chemotherapy
Other Name: Taxotere |
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Experimental: Stage 1 and 2: Etrumadenant + zimberelimab
Oral etrumadenant in combination IV zimberelimab
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Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist
Other Name: AB928 Drug: Zimberelimab Zimberelimab is an anti-PD-1 antibody
Other Name: AB122 |
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Experimental: Stage 2: Etrumadenant + zimberelimab + quemliclustat
Participants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat
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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 |
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Experimental: Stage 2: Etrumadenant + quemliclustat
Participants will receive oral etrumadenant in combination with IV quemliclustat
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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 |
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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.
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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 |
Primary Outcome Measures :
- 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
- 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 :
- 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
- 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
- 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).
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
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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
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
| Contact: Medical Director | +1-510-462-3330 | ClinicalTrialInquiry@arcusbio.com |
Locations
Show 20 study locations
Sponsors and Collaborators
Arcus Biosciences, Inc.
Gilead Sciences
| 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: | January 30, 2023 |
| Last Verified: | January 2023 |
| 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. |
| 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 |