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

NCT03628677 | Completed Phase 1 FDA Drug

• 1 other identifier: AB154CSP0001
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 10

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.

Conditions

Solid Tumor, Unspecified, Adult

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• AB154 Peak Plasma Concentration (Cmax)

  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)

  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)

  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)

  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)

  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

Other Outcomes (8)

• Domvanalimab Receptor Occupancy

  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

  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

  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

Study Arms (6)

Domvanalimab Monotherapy

EXPERIMENTAL

Varying Doses of domvanalimab Monotherapy

Drug: Domvanalimab

Domvanalimab + zimberelimab Q2W Combination Therapy

EXPERIMENTAL

Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Drug: Domvanalimab; Drug: Zimberelimab

Domvanalimab + zimberelimab Q3W Combination Therapy

EXPERIMENTAL

Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Drug: Domvanalimab; Drug: Zimberelimab

Domvanalimab + zimberelimab Q4W Combination Therapy

EXPERIMENTAL

Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Drug: Domvanalimab; Drug: Zimberelimab

Domvanalimab and Zimberelimab Q6W combination therapy

EXPERIMENTAL

Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Drug: Domvanalimab; Drug: Zimberelimab

Fixed dose Domvanalimab Q3W or Q4W and Zimberelimab Q3W, Q4W

EXPERIMENTAL

Varying Doses of domvanalimab in Combination With Varying Doses of zimberelimab

Drug: Domvanalimab; Drug: Zimberelimab

Interventions

Domvanalimab DRUG

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

Also known as: AB154

Domvanalimab + zimberelimab Q2W Combination Therapy; Domvanalimab + zimberelimab Q3W Combination Therapy; Domvanalimab + zimberelimab Q4W Combination Therapy; Domvanalimab Monotherapy; Domvanalimab and Zimberelimab Q6W combination therapy; Fixed dose Domvanalimab Q3W or Q4W and Zimberelimab Q3W, Q4W

Zimberelimab DRUG

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

Also known as: AB122

Domvanalimab + zimberelimab Q2W Combination Therapy; Domvanalimab + zimberelimab Q3W Combination Therapy; Domvanalimab + zimberelimab Q4W Combination Therapy; Domvanalimab and Zimberelimab Q6W combination therapy; Fixed dose Domvanalimab Q3W or Q4W and Zimberelimab Q3W, Q4W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Arcus Biosciences, Inc.: lead
• Gilead Sciences: collaborator

Study Sites (10)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Affinity Health-Hope and Healing Cancer Services, LLC

Hinsdale, Illinois, 60521, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

START

San Antonio, Texas, 78229, United States

Location

Medical Oncology Associates, PS (dba Summit Cancer Centers)

Spokane, Washington, 99208, United States

Location

The Kinghorn Cancer Centre - St Vincent Public Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Tweed Hospital

Tweed Heads, New South Wales, 2486, Australia

Location

Icon Cancer Care Brisbane

South Brisbane, Queensland, 4101, Australia

Location

Olivia Newton-John Cancer Research Institute-Austin Hostipal

Heidelberg, Victoria, 3084, Australia

Location

Related Links

• AB154CSP0001 - Public Website

MeSH Terms

Interventions

zimberelimab

Study Officials

• Medical Director

  Arcus Biosciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation Design

Study Record Dates

• First Submitted: July 26, 2018
• First Posted: August 14, 2018
• Study Start: September 12, 2018
• Primary Completion: January 23, 2025
• Study Completion: January 23, 2025
• Last Updated: February 4, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

US (6); AU (4)