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Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer

Phase 1
Active, not recruiting
Conditions
Androgen-Resistant Prostatic Neoplasms
Castration Resistant Prostatic Neoplasms
Prostatic Neoplasms, Castration-Resistant
Prostatic 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
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

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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamideEtrumadenantParticipants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide
Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamideZimberelimabParticipants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide
Stage 1 and 2: Etrumadenant + zimberelimab + docetaxelDocetaxelParticipants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel
Stage 2: Etrumadenant + zimberelimab + quemliclustatQuemliclustatParticipants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat
Stage 2: Etrumadenant + quemliclustatQuemliclustatParticipants will receive oral etrumadenant in combination with IV quemliclustat
Stage 1: Etrumadenant + zimberelimab PK Sub-StudyEtrumadenantParticipants will receive oral etrumadenant in combination with IV zimberelimab
Stage 1: Etrumadenant + zimberelimab PK Sub-StudyZimberelimabParticipants will receive oral etrumadenant in combination with IV zimberelimab
Stage 1 and 2: Etrumadenant + SGEtrumadenantParticipants will receive oral etrumadenant in combination with IV SG.
Stage 1 and 2: Etrumadenant + SGSGParticipants will receive oral etrumadenant in combination with IV SG.
Stage 1 and 2: Etrumadenant + Zimberelimab + SGEtrumadenantParticipants will receive oral etrumadenant in combination with IV zimberelimab and SG.
Stage 1 and 2: Etrumadenant + Zimberelimab + SGZimberelimabParticipants will receive oral etrumadenant in combination with IV zimberelimab and SG.
Stage 1 and 2: Etrumadenant + Zimberelimab + SGSGParticipants will receive oral etrumadenant in combination with IV zimberelimab and SG.
Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamideEnzalutamideParticipants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide
Stage 2: enzalutamideEnzalutamideParticipants will receive standard oral enzalutamide
Stage 1 and 2: Etrumadenant + zimberelimab + docetaxelZimberelimabParticipants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel
Stage 2: Etrumadenant + zimberelimab + quemliclustatZimberelimabParticipants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat
Stage 2: docetaxelDocetaxelParticipants will receive standard dose of IV docetaxel
Stage 1 and 2: Etrumadenant + zimberelimabEtrumadenantOral etrumadenant in combination IV zimberelimab
Stage 1 and 2: Etrumadenant + zimberelimabZimberelimabOral etrumadenant in combination IV zimberelimab
Stage 1 and 2: Etrumadenant + zimberelimab + docetaxelEtrumadenantParticipants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel
Stage 2: Etrumadenant + zimberelimab + quemliclustatEtrumadenantParticipants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat
Stage 2: Etrumadenant + quemliclustatEtrumadenantParticipants will receive oral etrumadenant in combination with IV quemliclustat
Primary Outcome Measures
NameTimeMethod
Incidence and Severity of AEs and Serious Adverse Events (SAEs) in Stage 1From first dose date to 90 days after the last dose (approximately 1.5 years)
Objective Response Rate (ORR) in Stage 1 and 2From 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
NameTimeMethod
Percentage of participants with a PSA response in Stage 1 and 2From 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 2From 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 2Recorded 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 2Recorded 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 2Recorded 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 2From 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 2Recorded 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 2From 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

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