Clinical Trials /

Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer

NCT04381832

Description:

This is a Phase 1b/2, open-label, multicenter platform trial to evaluate the antitumor activity and safety of AB928-based combination therapy in participants with metastatic castrate resistant prostate cancer (mCRPC).

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: ARC-6
  • NCT ID: NCT04381832

Conditions

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

Interventions

DrugSynonymsArms
AB928Stage 1 and 2: AB928 + AB680
ZimberelimabAB122Stage 1 and 2: AB928 + zimberelimab
AB680Stage 1 and 2: AB928 + AB680
EnzalutamideXtandiStage 1 and 2: AB928 + zimberelimab + enzalutamide
DocetaxelTaxotereStage 1 and 2: AB928 + zimberelimab + docetaxel

Purpose

This is a Phase 1b/2, open-label, multicenter platform trial to evaluate the antitumor activity and safety of 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 -
      AB928 plus zimberelimab alone, AB928 plus zimberelimab with or without a standard of care
      treatment (enzalutamide or docetaxel), or AB928 plus AB680 with or without zimberelimab will
      be administered to participants with mCRPC.

      During Stage 2 - Additional participants with mCRPC may receive an AB928-based combination
      therapy evaluated in Stage 1 or, a standard of care treatment.

      A pharmacokinetic (PK) Sub-Study (AB928 plus zimberelimab) will be conducted separately.

      Treatment may continue until unacceptable toxicity or progressive disease, or other reasons
      specified in the protocol.
    

Trial Arms

NameTypeDescriptionInterventions
Stage 1 and 2: AB928 + zimberelimab + enzalutamideExperimentalParticipants will receive oral AB928 in combination with intravenous (IV) zimberelimab and standard oral enzalutamide
  • AB928
  • Zimberelimab
  • Enzalutamide
Stage 2: enzalutamideActive ComparatorParticipants will receive standard oral enzalutamide
  • Enzalutamide
Stage 1 and 2: AB928 + zimberelimab + docetaxelExperimentalParticipants will receive oral AB928 in combination with IV zimberelimab and standard IV docetaxel
  • AB928
  • Zimberelimab
  • Docetaxel
Stage 2: docetaxelActive ComparatorParticipants will receive standard dose of IV docetaxel
  • Docetaxel
Stage 1 and 2: AB928 + zimberelimabExperimentalOral AB928 in combination IV zimberelimab
  • AB928
  • Zimberelimab
Stage 1 and 2: AB928 + zimberelimab + AB680ExperimentalParticipants will receive oral AB928 in combination with IV zimberelimab and IV AB680
  • AB928
  • Zimberelimab
  • AB680
Stage 1 and 2: AB928 + AB680ExperimentalParticipants will receive oral AB928 in combination with IV AB680
  • AB928
  • AB680
Stage 1: AB928 + zimberelimab PK Sub-StudyExperimentalParticipants will receive oral AB928 in combination with IV zimberelimab
  • AB928
  • Zimberelimab

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 nmol/L or 50 ng/dL)

          -  Measurable or non-measurable disease as per radiographic evaluation

          -  Participants with measurable disease may require a fresh tumor biopsy at study entry

          -  Performance status of 0 or 1

          -  Life expectancy of at least 3 months

          -  Adequate hematologic and end-organ function

          -  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

          -  ECG (Electrocardiogram) result with QTcF ≥480 msec

          -  Prior 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 oral medications

          -  HIV, Hepatitis B, and C test results negative prior to first study treatment

          -  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 3 or more lines of 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR), defined as the composite proportion of participants with a PSA and/or radiographic complete and partial response determined by the investigator according to the Prostate Cancer Working Group 3 (PCWG3) criteria
Time Frame:From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 1 year)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Proportion of participants with a 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
Time Frame:From study enrollment until disease progression or loss of clinical benefit (approximately 1 year)
Safety Issue:
Description:
Measure:Proportion of participants with 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
Time Frame:From study enrollment until disease progression or loss of clinical benefit (approximately 1 year)
Safety Issue:
Description:
Measure:Percentage of Participants with measurable disease at baseline who achieved a best overall RECIST response of CR, PR, or SD
Time Frame:From study enrollment until disease progression or loss of clinical benefit (approximately 1 year)
Safety Issue:
Description:
Measure:Serum/ Plasma Concentration AB928, zimberelimab, and enzalutamide when administered as part of a combination regimen in Stage 1 & 2.
Time Frame:Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treament. (approximately 1 year)
Safety Issue:
Description:
Measure:Serum/Plasma Concentration for AB928 and zimberelimab when administered as part of a combination regimen with docetaxel in Stage 1 & 2.
Time Frame:Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1 year)
Safety Issue:
Description:
Measure:Serum/Plasma Concentration for AB928 and zimberelimab when administered as part of a combination regimen in Stage 1 & 2.
Time Frame:Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1 year)
Safety Issue:
Description:
Measure:Serum/Plasma Concentration for AB928, zimberelimab, and AB680 when administered as part of a combination regimen in Stage 1 & 2.
Time Frame:Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1 year)
Safety Issue:
Description:
Measure:Serum/Plasma Concentration for AB928 and AB680 when administered as part of a combination regimen in Stage 1 & 2.
Time Frame:Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1 year)
Safety Issue:
Description:
Measure:Percentage of participants with anti-drug antibodies to zimberelimab
Time Frame:Recorded at baseline (enrollment), during the first 4 months of treatment, 4 additional timepoints in the first year of treament, and at end of treatment. (approximately 1 year)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Arcus Biosciences, Inc.

Last Updated

May 27, 2020