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

A Phase 1 Study to Evaluate the Safety and Tolerability of AB154 Monotherapy and Combination Therapy 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumor, Unspecified, Adult
• Intervention / Treatment: Drug: Domvanalimab; Drug: Zimberelimab

Detailed Description

This is a Phase 1, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, PK, PD, and clinical activity of domvanalimab as monotherapy and in combination with zimberelimab in participants with advanced solid malignancies. In this dose escalation study, participants will receive domvanalimab 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: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Albury, Australia
    • Camperdown, New South Wales, Australia, 2050
      • Principal Investigator
    • Darlinghurst, New South Wales, Australia, 2010
      • The Kinghorn Cancer Centre
    • Randwick, New South Wales, Australia, 2031
      • Scientia Clinical Research
    • Tweed Heads, New South Wales, Australia, 2480
      • Principal Investigator
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Principal Investigator
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Olivia Newton-John Cancer Research Institute
• United States
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • START
  • Washington
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates, PS (dba Summit Cancer Centers)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 100 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Domvanalimab Monotherapy; Varying Doses of domvanalimab Monotherapy	Drug: Domvanalimab; Domvanalimabis a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT; Other Names: AB154
Experimental: Domvanalimab + zimberelimab Q2W Combination Therapy; Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab	Drug: Domvanalimab; Domvanalimabis a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT; Other Names: AB154; Drug: Zimberelimab; Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1; Other Names: AB122
Experimental: Domvanalimab + zimberelimab Q3W Combination Therapy; Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab	Drug: Domvanalimab; Domvanalimabis a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT; Other Names: AB154; Drug: Zimberelimab; Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1; Other Names: AB122
Experimental: Domvanalimab + zimberelimab Q4W Combination Therapy; Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab	Drug: Domvanalimab; Domvanalimabis a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT; Other Names: AB154; Drug: Zimberelimab; Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1; Other Names: AB122
Experimental: Domvanalimab and Zimberelimab Q6W combination therapy; Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab	Drug: Domvanalimab; Domvanalimabis a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT; Other Names: AB154; Drug: Zimberelimab; Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1; Other Names: AB122
Experimental: Fixed dose Domvanalimab Q3W or Q4W and Zimberelimab Q3W, Q4W; Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab	Drug: Domvanalimab; Domvanalimabis a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting human TIGIT; Other Names: AB154; Drug: Zimberelimab; Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1; Other Names: AB122

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0	Number of Participants Treated with domvanalimab or domvanalimab in Combination with zimberelimab with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0	From First Dose Date to 100 Days After Last Dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AB154 Peak Plasma Concentration (Cmax)	Peak Plasma Concentration (Cmax) of domvanalimab	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
Zimberelimab Peak Plasma Concentration (Cmax)	Peak Plasma Concentration (Cmax) of zimberelimab	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
Domvanalimab Time of Peak Concentration (Tmax)	Time of Peak Concentration (Tmax) of domvanalimab	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
Zimberelimab Time of Peak Concentration (Tmax)	Time of Peak Concentration (Tmax) of zimberelimab	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
Domvanalimab Area Under the Plasma Concentration Versus Time Curve (AUC)	Area Under the Plasma Concentration Versus Time Curve (AUC) of domvanalimab	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
Zimberelimab Area Under the Plasma Concentration Versus Time Curve (AUC)	Area Under the Plasma Concentration Versus Time Curve (AUC) of zimberelimab	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
Immunogenicity Indicators: Anti-Drug Antibodies (ADA)	Number of Participants who Develop Antidrug Antibodies to AB154 and/or AB122	Day 1, Day 15, Day 29, Day 43, Day 57, Day 85 and 30 Days After Last Dose, up to 52 weeks
Overall Response Rate	Number of Participants with Complete or Partial Response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.1	First Dose Date to Progression or Last Tumor Assessment, up to 1 year
Duration of Response	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	Start Date of Response to First Progression/Death, up to 1 year
Disease Control Rate	Number of Participants with Complete Response, Partial Response, or Stable Disease for Greater Than 6 Months per RECIST v1.1	First Dose Date to First Progression/Death, up to 1 year
Progression Free Survival	Number of Participants Without Disease Progression per RECIST v1.1	First Dose Date to First Progression/Death, up to 1 year
Overall Survival	Overall Survival Rate, Defined as Time Between First Dose Date and Date of Death	First Dose Date to Date of Death, up to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Domvanalimab Receptor Occupancy	Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	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
Domvanalimab Immunophenotyping	Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	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
Domvanalimab Gene Expression	Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	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
Domvanalimab Cytokines	Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples.	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
.Zimberelimab Receptor Occupancy	Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	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
Zimberelimab Immunophenotyping	Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	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
Zimberelimab Cytokines	Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	: 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
Zimberelimab Gene Expression	Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples	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

Collaborators and Investigators

• Sponsor: Arcus Biosciences, Inc.
• Collaborators: Gilead Sciences
• Investigators: Study Director: Medical Director, Arcus Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2018
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: July 26, 2018
• First Submitted That Met QC Criteria: August 10, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AB154CSP0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Arcus will provide access to individual de-identified participant data and related study documents [e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)] upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.

For more information, please visit our website.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No