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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 : October 1, 2018
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

Study Description
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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 AB122 in participants with advanced solid malignancies.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Squamous Cell Carcinoma of the Head and Neck Renal Cell Carcinoma Breast Cancer Colorectal Cancer Melanoma Bladder Cancer Ovarian Cancer Endometrial Cancer Merkel Cell Carcinoma GastroEsophageal Cancer Drug: AB154 Drug: AB122 Phase 1

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 AB122 in participants with advanced solid malignancies. In this dose escalation study, participants will receive AB154 administered intravenously as monotherapy or in combination with AB122. Treatment will continue until progressive disease, unacceptable toxicity, withdrawal of consent, or other reasons for study drug discontinuation occurs.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 3+3 Dose Escalation Design
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study to Evaluate the Safety and Tolerability of AB154 Monotherapy and Combination Therapy in Participants With Advanced Malignancies
Actual Study Start Date : August 21, 2018
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : February 15, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: AB154 Monotherapy
Varying Doses of AB154 Monotherapy
 Drug: AB154
AB154 is a fully humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT
Experimental: AB154 + AB122 Combination Therapy
Varying Doses of AB154 in Combination With the Selected Dose of AB122
 Drug: AB154
AB154 is a fully humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT

Drug: AB122
AB122 is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Pathologically confirmed non-small cell lung cancer, squamous cell carcinoma of the head and neck, renal cell carcinoma, breast cancer, colorectal cancer, melanoma, bladder cancer, ovarian cancer, endometrial cancer, Merkel cell carcinoma, or gastroesophageal cancer that is metastatic, advanced, or recurrent with progression for which no alternative or curative therapy exists or standard therapy is not considered appropriate by the participant and treating physician
  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. Must have received standard of care, including potentially curative available therapies or interventions
  8. Confirmation that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor must be obtained
  9. Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) or biologic agents must have been completed at least 4 weeks before investigational product administration, and all AEs have either returned to baseline or stabilized
  10. 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
  11. 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
  12. 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
  13. 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. 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
  5. 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03628677


Contacts
Contact: Medical Director 510-694-6200 ClinicalTrialInquiry@arcusbio.com

Locations
Australia, New South Whales
Scientia Clinical Research Recruiting
Randwick, New South Whales, Australia, 2031
Contact: James Kuo, MD         
Principal Investigator: James Kuo, MD         
Sponsors and Collaborators
Arcus Biosciences, Inc.
Investigators
Study Director: Medical Director Arcus Biosciences, Inc.
More Information
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Responsible Party: Arcus Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT03628677     History of Changes
Other Study ID Numbers: AB154CSP0001
First Posted: August 14, 2018    Key Record Dates
Last Update Posted: October 1, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Carcinoma, Squamous Cell
Urinary Bladder Neoplasms
Carcinoma, Renal Cell
Endometrial Neoplasms
Head and Neck Neoplasms
Carcinoma, Merkel Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
 Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Squamous Cell
Urologic Neoplasms