Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer

Prostatic Neoplasms, Castration-Resistant Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04381832
• Other study ID #: ARC-6
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 7, 2020
• Est. completion date: August 2024

Study information

• Verified date: May 2024
• Source: Arcus Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 173
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist
• Zimberelimab
Zimberelimab is an anti-PD-1 antibody
• Quemliclustat
Quemliclustat is a Cluster of Differentiation (CD)73 Inhibitor.
• Enzalutamide
Enzalutamide is an androgen receptor inhibitor
• Docetaxel
Docetaxel is type of chemotherapy
• SG
Sacituzumab govitecan is an antibody-drug conjugate

Locations

Country	Name	City	State
Canada	Juravinski Cancer Center	Hamilton	Ontario
Canada	Centre hospitalier de l'Université de Montréal (CHUM) Centre de Recherche	Montréal	Quebec
United States	Johns Hopkins University	Baltimore	Maryland
United States	The Oncology Institute of Hope & Innovation	Cerritos	California
United States	Tennessee Oncology - Chattanooga	Chattanooga	Tennessee
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	The University of California, Los Angeles	Encino	California
United States	Affinity Health Hope & Healing Cancer Services	Hinsdale	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Tennessee Oncology - Nashville	Nashville	Tennessee
United States	New York University, Langone Health	New York	New York
United States	The University of California, Irvine Medical Center	Orange	California
United States	Wilmot Cancer Institute Oncology, University of Rochester	Rochester	New York
United States	Florida Cancer Specialists North	Saint Petersburg	Florida
United States	The University of California, San Francisco	San Francisco	California
United States	Florida Cancer Specialists South	Sarasota	Florida
United States	Medical Oncology Associates, PS (dba Summit Cancer Centers)	Spokane	Washington
United States	Florida Cancer Specialists Panhandle	Tallahassee	Florida
United States	Florida Cancer Specialists East	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Arcus Biosciences, Inc.	Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)