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

• ClinicalTrials.gov Identifier: NCT03628677
• Recruitment Status: Active, not recruiting
• First Posted: August 14, 2018
• Last Update Posted: May 3, 2022
• Sponsor: Arcus Biosciences, Inc.
• Information provided by (Responsible Party): Arcus Biosciences, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Solid Tumor, Unspecified, Adult	Drug: Domvanalimab; Drug: Zimberelimab	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 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 75 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: 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: September 12, 2018
• Estimated Primary Completion Date: October 1, 2022
• Estimated Study Completion Date: October 1, 2022

Arms and Interventions

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 Name: 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 Name: AB154; Drug: Zimberelimab; Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1; Other Name: 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 Name: AB154; Drug: Zimberelimab; Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1; Other Name: 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 Name: AB154; Drug: Zimberelimab; Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1; Other Name: 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 Name: AB154; Drug: Zimberelimab; Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1; Other Name: 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 Name: AB154; Drug: Zimberelimab; Zimbererlimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1; Other Name: AB122

Outcome Measures

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 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 Outcome Measures :

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 Outcome Measures:

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

Eligibility Criteria

• 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. 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. 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
9. 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
10. 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 domvanalimab as monotherapy and in combination with zimberelimab.
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, 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
9. Use of other investigational drugs within 28 days or at least 5 half-lives before investigational product administration.

Contacts and Locations

Locations

United States, California

The Angeles Clinic and Research Institute

Los Angeles, California, United States, 90025

United States, North Carolina

Carolina BioOncology Institute

Huntersville, North Carolina, United States, 28078

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

START

San Antonio, Texas, United States, 78229

United States, Washington

Medical Oncology Associates, PS (dba Summit Cancer Centers)

Spokane, Washington, United States, 99208

Australia, New South Wales

Albury, Australia

Albury, New South Wales, Australia, 2640

Principal Investigator

Camperdown, New South Wales, Australia, 2050

The Kinghorn Cancer Centre

Darlinghurst, New South Wales, Australia, 2010

Scientia Clinical Research

Randwick, New South Wales, Australia, 2031

Principal Investigator

Tweed Heads, New South Wales, Australia, 2480

Australia, Queensland

Principal Investigator

South Brisbane, Queensland, Australia, 4101

Australia, Victoria

Olivia Newton-John Cancer Research Institute

Heidelberg, Victoria, Australia, 3084

Sponsors and Collaborators

Arcus Biosciences, Inc.

Investigators

• Study Director: Medical Director; Arcus Biosciences, Inc.

More Information

• Responsible Party: Arcus Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT03628677
• Other Study ID Numbers: AB154CSP0001
• First Posted: August 14, 2018
• Last Update Posted: May 3, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.

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

Additional relevant MeSH terms:

Neoplasms