Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer
- Conditions
- Androgen-Resistant Prostatic NeoplasmsCastration Resistant Prostatic NeoplasmsProstatic Neoplasms, Castration-ResistantProstatic Cancer, Castration-Resistant
- Interventions
- Registration Number
- NCT04381832
- Lead Sponsor
- Arcus Biosciences, Inc.
- 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).
- Detailed 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 & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 173
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamide Etrumadenant Participants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamide Zimberelimab Participants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide Stage 1 and 2: Etrumadenant + zimberelimab + docetaxel Docetaxel Participants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel Stage 2: Etrumadenant + zimberelimab + quemliclustat Quemliclustat Participants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat Stage 2: Etrumadenant + quemliclustat Quemliclustat Participants will receive oral etrumadenant in combination with IV quemliclustat Stage 1: Etrumadenant + zimberelimab PK Sub-Study Etrumadenant Participants will receive oral etrumadenant in combination with IV zimberelimab Stage 1: Etrumadenant + zimberelimab PK Sub-Study Zimberelimab Participants will receive oral etrumadenant in combination with IV zimberelimab Stage 1 and 2: Etrumadenant + SG Etrumadenant Participants will receive oral etrumadenant in combination with IV SG. Stage 1 and 2: Etrumadenant + SG SG Participants will receive oral etrumadenant in combination with IV SG. Stage 1 and 2: Etrumadenant + Zimberelimab + SG Etrumadenant Participants will receive oral etrumadenant in combination with IV zimberelimab and SG. Stage 1 and 2: Etrumadenant + Zimberelimab + SG Zimberelimab Participants will receive oral etrumadenant in combination with IV zimberelimab and SG. Stage 1 and 2: Etrumadenant + Zimberelimab + SG SG Participants will receive oral etrumadenant in combination with IV zimberelimab and SG. Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamide Enzalutamide Participants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide Stage 2: enzalutamide Enzalutamide Participants will receive standard oral enzalutamide Stage 1 and 2: Etrumadenant + zimberelimab + docetaxel Zimberelimab Participants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel Stage 2: Etrumadenant + zimberelimab + quemliclustat Zimberelimab Participants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat Stage 2: docetaxel Docetaxel Participants will receive standard dose of IV docetaxel Stage 1 and 2: Etrumadenant + zimberelimab Etrumadenant Oral etrumadenant in combination IV zimberelimab Stage 1 and 2: Etrumadenant + zimberelimab Zimberelimab Oral etrumadenant in combination IV zimberelimab Stage 1 and 2: Etrumadenant + zimberelimab + docetaxel Etrumadenant Participants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel Stage 2: Etrumadenant + zimberelimab + quemliclustat Etrumadenant Participants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat Stage 2: Etrumadenant + quemliclustat Etrumadenant Participants will receive oral etrumadenant in combination with IV quemliclustat
- Primary Outcome Measures
Name Time Method 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) 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
- Secondary Outcome Measures
Name Time Method 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
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
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 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) 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, 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) 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) 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)
Trial Locations
- Locations (19)
Florida Cancer Specialists East
🇺🇸West Palm Beach, Florida, United States
The Oncology Institute of Hope & Innovation
🇺🇸Cerritos, California, United States
The University of California, Los Angeles
🇺🇸Encino, California, United States
The University of California, Irvine Medical Center
🇺🇸Orange, California, United States
Florida Cancer Specialists North
🇺🇸Saint Petersburg, Florida, United States
Florida Cancer Specialists South
🇺🇸Sarasota, Florida, United States
Florida Cancer Specialists Panhandle
🇺🇸Tallahassee, Florida, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Affinity Health Hope & Healing Cancer Services
🇺🇸Hinsdale, Illinois, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
New York University, Langone Health
🇺🇸New York, New York, United States
Wilmot Cancer Institute Oncology, University of Rochester
🇺🇸Rochester, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Tennessee Oncology - Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Tennessee Oncology - Nashville
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Medical Oncology Associates, PS (dba Summit Cancer Centers)
🇺🇸Spokane, Washington, United States
Juravinski Cancer Center
🇨🇦Hamilton, Ontario, Canada
Centre hospitalier de l'Université de Montréal (CHUM) Centre de Recherche
🇨🇦Montreal, Quebec, Canada