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Completed

NCT Number: NCT03628677

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

This is a Phase 1, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, PK, PD, and clinical activity of domvanalimab (AB154) as monotherapy and in combination with zimberelimab (AB122) in participants with advanced solid malignancies.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

The Kinghorn Cancer Centre - St Vincent Public Hospital, Darlinghurst, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Capable of giving signed informed consent
  • Male or female participants ≥ 18 years of age at the time of screening
  • 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
  • Participants with any pathologically confirmed solid tumor type for which no standard of care therapy exists
  • 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
  • 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. 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
  • 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
  • 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
  • Adequate organ and marrow function

Exclusion criteria

  • Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product
  • 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)
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • 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 120 days after the last dose of domvanalimab as monotherapy and in combination with zimberelimab.
  • Participants who require a Legally Authorized Representative (LAR) to provide informed consent on their behalf.
  • 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
  • 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
  • Has had prior chemotherapy, targeted small-molecule therapy, immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer), biologic agents or radiation therapy within 4 weeks (or 5 half-lives) prior to Day 1 or has not recovered from AEs due to a previously administered agent
  • Use of other investigational drugs within 28 days or at least 5 half-lives before investigational product administration.

Treatment and study plan

Domvanalimab

Drug

Domvanalimabis a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT

Other names: AB154

Zimberelimab

Drug

Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1

Other names: AB122

Primary outcomes

  1. Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0

    Time frame: From First Dose Date to 100 Days After Last Dose

    Number of Participants Treated with domvanalimab or domvanalimab in Combination with zimberelimab with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0

Secondary outcomes

  1. 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 domvanalimab

  2. 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

  3. Domvanalimab 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 domvanalimab

  4. 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

  5. Domvanalimab 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 domvanalimab

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

Other outcomes

  1. Domvanalimab 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, Day 106, Day 141 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

  2. Domvanalimab 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, Day 106, Day 141 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

  3. Domvanalimab 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

  4. Domvanalimab 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, Day 106, Day 141 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.

  5. .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, Day 106, Day 141 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

  6. 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, Day 106, Day 141 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

  7. 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, Day 106, Day 141 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

  8. 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

Sponsors and collaborators

Lead sponsor

Arcus Biosciences, Inc.

Industry

Collaborators

  • Gilead Sciences

Registry information

Official study title

A Phase 1 Study to Evaluate the Safety and Tolerability of AB154 Monotherapy and Combination Therapy in Participants With Advanced Malignancies

Important dates

Study start
2018
Primary completion
2025
Study completion
2025
First posted
Aug 14, 2018
Registry last updated
Feb 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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