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A Study to Evaluate the Safety and Tolerability of AB154 in Participants With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT03628677
Recruitment Status : Recruiting
First Posted : August 14, 2018
Last Update Posted : September 4, 2020
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

Tracking Information
First Submitted Date  ICMJE July 26, 2018
First Posted Date  ICMJE August 14, 2018
Last Update Posted Date September 4, 2020
Actual Study Start Date  ICMJE September 12, 2018
Estimated Primary Completion Date July 7, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 10, 2018)		 Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0 [ Time Frame: From First Dose Date to 6 Months After Last Dose ]
Number of Participants Treated with AB154 or AB154 in Combination with AB122 with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2020)
  • AB154 Peak Plasma Concentration (Cmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks ]
    Peak Plasma Concentration (Cmax) of AB154
  • Zimberelimab Peak Plasma Concentration (Cmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks ]
    Peak Plasma Concentration (Cmax) of zimberelimab
  • AB154 Time of Peak Concentration (Tmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks ]
    Time of Peak Concentration (Tmax) of AB154
  • Zimberelimab Time of Peak Concentration (Tmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks ]
    Time of Peak Concentration (Tmax) of zimberelimab
  • AB154 Area Under the Plasma Concentration Versus Time Curve (AUC) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks ]
    Area Under the Plasma Concentration Versus Time Curve (AUC) of AB154
  • Zimberelimab Area Under the Plasma Concentration Versus Time Curve (AUC) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 113, Day 141 and 30 Days After Last Dose, up to 52 weeks ]
    Area Under the Plasma Concentration Versus Time Curve (AUC) of zimberelimab
  • AB154 Receptor Occupancy [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB154 Immunophenotyping [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB154 Gene Expression [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB154 Cytokines [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • Zimberelimab Receptor Occupancy [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • Zimberelimab Immunophenotyping [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • Zimberelimab Cytokines [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • Zimberelimab Gene Expression [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22, Day 29, Day 31, Day 36, Day 43, Day 57, Day 64, Day 85, Day 106, Day 141, and 30 Days After Last Dose, up to 52 weeks ]
    Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • Immunogenicity Indicators: Anti-Drug Antibodies (ADA) [ Time Frame: Day 1, Day 15, Day 29, Day 43, Day 57, Day 85 and 30 Days After Last Dose, up to 52 weeks ]
    Number of Participants who Develop Antidrug Antibodies to AB154 and/or AB122
  • Overall Response Rate [ Time Frame: First Dose Date to Progression or Last Tumor Assessment, up to 1 year ]
    Number of Participants with Complete or Partial Response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.1
  • Duration of Response [ Time Frame: Start Date of Response to First Progression/Death, up to 1 year ]
    Time at Which Response Criteria are Met for Complete Response or Partial Response (Whichever Occurs First) Until the First Date of Recurrence, Progression or Death per RECIST v1.1
  • Disease Control Rate [ Time Frame: First Dose Date to First Progression/Death, up to 1 year ]
    Number of Participants with Complete Response, Partial Response, or Stable Disease for Greater Than 6 Months per RECIST v1.1
  • Progression Free Survival [ Time Frame: First Dose Date to First Progression/Death, up to 1 year ]
    Number of Participants Without Disease Progression per RECIST v1.1
  • Overall Survival [ Time Frame: First Dose Date to Date of Death, up to 1 year ]
    Overall Survival Rate, Defined as Time Between First Dose Date and Date of Death
Original Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2018)
  • AB154 Peak Plasma Concentration (Cmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Peak Plasma Concentration (Cmax) of AB154
  • AB122 Peak Plasma Concentration (Cmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Peak Plasma Concentration (Cmax) of AB122
  • AB154 Time of Peak Concentration (Tmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Time of Peak Concentration (Tmax) of AB154
  • AB122 Time of Peak Concentration (Tmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Time of Peak Concentration (Tmax) of AB122
  • AB154 Area Under the Plasma Concentration Versus Time Curve (AUC) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Area Under the Plasma Concentration Versus Time Curve (AUC) of AB154
  • AB122 Area Under the Plasma Concentration Versus Time Curve (AUC) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29 (sequential), Day 30, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Area Under the Plasma Concentration Versus Time Curve (AUC) of AB122
  • AB154 Receptor Occupancy [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB154 Immunophenotyping [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB154 Gene Expression [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB154 Cytokines [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB122 Receptor Occupancy [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB122 Immunophenotyping [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB122 Cytokines [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB122 Gene Expression [ Time Frame: Day 1, Day 3, Day 8, Day 15, Day 29, Day 31, Day 36, Day 43, Day 57, Day 85, and 30 Days After Last Dose, up to 52 weeks ]
    Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • Immunogenicity Indicators: Anti-Drug Antibodies (ADA) [ Time Frame: Day 1, Day 15, Day 29, Day 43, Day 57, Day 85 and 30 Days After Last Dose, up to 52 weeks ]
    Number of Participants who Develop Antidrug Antibodies to AB154 and/or AB122
  • Overall Response Rate [ Time Frame: First Dose Date to Progression or Last Tumor Assessment, up to 1 year ]
    Number of Participants with Complete or Partial Response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.1
  • Duration of Response [ Time Frame: Start Date of Response to First Progression/Death, up to 1 year ]
    Time at Which Response Criteria are Met for Complete Response or Partial Response (Whichever Occurs First) Until the First Date of Recurrence, Progression or Death per RECIST v1.1
  • Disease Control Rate [ Time Frame: First Dose Date to First Progression/Death, up to 1 year ]
    Number of Participants with Complete Response, Partial Response, or Stable Disease for Greater Than 6 Months per RECIST v1.1
  • Progression Free Survival [ Time Frame: First Dose Date to First Progression/Death, up to 1 year ]
    Number of Participants Without Disease Progression per RECIST v1.1
  • Overall Survival [ Time Frame: First Dose Date to Date of Death, up to 1 year ]
    Overall Survival Rate, Defined as Time Between First Dose Date and Date of Death
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety and Tolerability of AB154 in Participants With Advanced Malignancies
Official Title  ICMJE A Phase 1 Study to Evaluate the Safety and Tolerability of AB154 Monotherapy and Combination Therapy in Participants With Advanced Malignancies
Brief Summary This is a Phase 1, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, PK, PD, and clinical activity of AB154 as monotherapy and in combination with zimberelimab (AB122) in participants with advanced solid malignancies.
Detailed Description This is a Phase 1, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, PK, PD, and clinical activity of AB154 as monotherapy and in combination with zimberelimab in participants with advanced solid malignancies. In this dose escalation study, participants will receive AB154 administered intravenously as monotherapy or in combination with zimberelimab. Treatment will continue until progressive disease, unacceptable toxicity, withdrawal of consent, or other reasons for study drug discontinuation occurs.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Dose Escalation Design
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor, Unspecified, Adult
Intervention  ICMJE
  • Drug: AB154
    AB154 is a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT
  • Drug: Zimberelimab
    Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1
    Other Name: AB122
Study Arms  ICMJE
  • Experimental: AB154 Monotherapy
    Varying Doses of AB154 Monotherapy
    Intervention: Drug: AB154
  • Experimental: AB154 + zimberelimab Q2W Combination Therapy
    Varying Doses of AB154 in Combination With Varying Doses of zimberelimab
    Interventions:
    • Drug: AB154
    • Drug: Zimberelimab
  • Experimental: AB154 + zimberelimab Q3W Combination Therapy
    Varying Doses of AB154 in Combination With Varying Doses of zimberelimab
    Interventions:
    • Drug: AB154
    • Drug: Zimberelimab
  • Experimental: AB154 + zimberelimab Q4W Combination Therapy
    Varying Doses of AB154 in Combination With Varying Doses of zimberelimab
    Interventions:
    • Drug: AB154
    • Drug: Zimberelimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 22, 2020)		 66
Original Estimated Enrollment  ICMJE
 (submitted: August 10, 2018)		 42
Estimated Study Completion Date  ICMJE November 10, 2021
Estimated Primary Completion Date July 7, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Capable of giving signed informed consent
  2. Male or female participants ≥ 18 years of age at the time of screening
  3. Negative serum pregnancy test at screening and prior to dosing on Cycle 1 Day 1; negative serum or urine pregnancy test on the first day of each subsequent treatment period
  4. Participants with any pathologically confirmed solid tumor type for which no standard of care therapy exists
  5. Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The measurable lesion must be outside of a radiation field if the participant received prior radiation
  6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  7. Confirmation that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor must be obtained
  8. Prior chemotherapy, targeted small-molecule therapy, immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) or biologic agents must have been discontinued at least 4 weeks before investigational product administration, and all AEs have either returned to baseline or ≤ Grade 1
  9. Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed topical corticosteroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks (14 days) before investigational product administration. Physiologic doses of corticosteroids ≤ 10 mg/day of prednisone or its equivalent may be permitted
  10. Prior surgery that required general anesthesia or other major surgery as defined by the Investigator must be completed at least 4 weeks before investigational product administration
  11. Negative tests for hepatitis B surface antigen, hepatitis C virus antibody (or hepatitis C qualitative ribonucleic acid [RNA; qualitative]), and human immunodeficiency virus (HIV)-1 and HIV-2 antibody at screening
  12. Adequate organ and marrow function

Exclusion Criteria:

  1. Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product
  2. Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational product hazardous (eg, interstitial lung disease, active infections requiring antibiotics, recent hospitalization with unresolved symptoms)
  3. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  4. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 100 days after the last dose of AB154 as monotherapy and in combination with AB122.
  5. Participants who require a Legally Authorized Representative (LAR) to provide informed consent on their behalf.
  6. Any active autoimmune disease or a documented history of autoimmune disease or history of a syndrome that required systemic steroids or immunosuppressive medications, except for vitiligo or resolved childhood asthma/atopy. Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study
  7. Prior malignancy active within the previous year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer
  8. Has had prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 2 weeks prior to Day 1 or has not recovered from AEs due to a previously administered agent
  9. Use of other investigational drugs within 28 days or at least 5 half-lives before investigational product administration.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Director 510-694-6220 ClinicalTrialInquiry@arcusbio.com
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03628677
Other Study ID Numbers  ICMJE AB154CSP0001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Arcus Biosciences, Inc.
Study Sponsor  ICMJE Arcus Biosciences, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Arcus Biosciences, Inc.
PRS Account Arcus Biosciences, Inc.
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP