Prostatic Neoplasms, Castration-Resistant, Androgen-Resistant Prostatic Neoplasms, Castration Resistant Prostatic Neoplasms, Prostatic Cancer, Castration-Resistant
Conditions
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).
Interventions
DRUGEtrumadenant
Etrumadenant is an A2aR and A2bR antagonist
DRUGZimberelimab
Zimberelimab is an anti-PD-1 antibody
DRUGQuemliclustat
Quemliclustat is a Cluster of Differentiation (CD)73 Inhibitor.
DRUGEnzalutamide
Enzalutamide is an androgen receptor inhibitor
DRUGDocetaxel
Docetaxel is type of chemotherapy
DRUGSG
Sacituzumab govitecan is an antibody-drug conjugate
Sponsors
Gilead Sciences
Arcus Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) in Stage 1 and 2 | 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 | From first dose date to 90 days after the last dose (approximately 1.5 years) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Disease Control Rate in Stage 1 and 2 | 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. | 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 | 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 | 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 a PSA response in Stage 1 and 2 | 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 |
| 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) | — |
| 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) | — |
| 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) | — |
| 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) | — |
| Percentage of participants with Radiographic Response in Stage 1 and 2 | 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 |
Countries
Canada, United States
Outcome results
None listed