Clinical trial NCT04381832: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostatic Neoplasms, Castration-Resistant
Androgen-Resistant Prostatic Neoplasms
Castration Resistant Prostatic Neoplasms
Prostatic Cancer, Castration-Resistant
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Gilead Sciences
First posted: 2020-05-11
Enrollment: 173
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Objective Response Rate (ORR) in Stage 1 and 2
timeFrame: From study enrolment until participant discontinuation, or first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 3-5 years)
measure: Incidence and Severity of AEs and Serious Adverse Events (SAEs) in Stage 1
timeFrame: From first dose date to 90 days after the last dose (approximately 1.5 years)
Secondary outcomes:
measure: Percentage of participants with a PSA response in Stage 1 and 2
timeFrame: From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years)
measure: Percentage of participants with Radiographic Response in Stage 1 and 2
timeFrame: From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years)
measure: Percentage of Participants with Disease Control Rate in Stage 1 and 2
timeFrame: From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years)
measure: Serum/Plasma Concentration for etrumadenant, zimberelimab, and enzalutamide when administered as part of a combination regimen in Stage 1 and 2.
timeFrame: 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)
measure: Serum/Plasma Concentration for etrumadenant and zimberelimab when administered as part of a combination regimen with docetaxel in Stage 1 and 2
timeFrame: 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)
measure: Serum/Plasma Concentration for etrumadenant and zimberelimab when administered as part of a combination regimen in Stage 1 and 2
timeFrame: 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)
measure: Serum/Plasma Concentration for etrumadenant, zimberelimab, and AB680 when administered as part of a combination regimen in Stage 1 and 2
timeFrame: 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)
measure: Serum/Plasma Concentration for etrumadenant and AB680 when administered as part of a combination regimen in Stage 1 and 2.
timeFrame: 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)
measure: Percentage of participants with anti-drug antibodies to zimberelimab in Stage 1 and 2
timeFrame: 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)
measure: Incidence and severity of AEs and serious adverse events (SAEs) in Stage 2
timeFrame: From first dose date to 90 days after the last dose (approximately 3-5 years)
Other outcomes:
Locations:
city: Cerritos
country: United States
facility: The Oncology Institute of Hope & Innovation
state: California
city: Encino
country: United States
facility: The University of California, Los Angeles
state: California
city: Orange
country: United States
facility: The University of California, Irvine Medical Center
state: California
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists North
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists South
state: Florida
city: Tallahassee
country: United States
facility: Florida Cancer Specialists Panhandle
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists East
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Hinsdale
country: United States
facility: Affinity Health Hope & Healing Cancer Services
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: New York
country: United States
facility: New York University, Langone Health
state: New York
city: Rochester
country: United States
facility: Wilmot Cancer Institute Oncology, University of Rochester
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Chattanooga
country: United States
facility: Tennessee Oncology - Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology - Nashville
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates, PS (dba Summit Cancer Centers)
state: Washington
city: Hamilton
country: Canada
facility: Juravinski Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: Centre hospitalier de l'Université de Montréal (CHUM) Centre de Recherche
state: Quebec
Study officials:
affiliation: Arcus Biosciences
name: Medical Director
role: STUDY_DIRECTOR
References: