Study to Evaluate Safety and Clinical Activity of AB122 in Biomarker Selected Participants With Advanced Solid Tumors

A Phase 1b Study to Evaluate the Safety and Clinical Activity of AB122 in Biomarker-Selected Participants With Advanced Solid Tumors

This is a Phase 1b open-label study to evaluate the safety and clinical activity of zimberelimab (AB122) in biomarker-selected participants with advanced solid tumors.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: zimberelimab

Detailed Description

The activity of zimberelimab every 3 weeks (Q3W) will be evaluated in molecularly defined patient populations as described by the StrataNGS test (to be performed outside of this study protocol). Participants with any advanced tumor type will be stratified evenly by tumor biomarker status as follows: TMB-H or Strata Immune Signature positive. Each cohort may enroll approximately 40 participants. Following completion of and/or discontinuation from investigational product and follow-up, all participants will be followed for survival.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Riverside, California, United States, 92120
      • Southern California Permanente Medical Group
    • Roseville, California, United States, 95661
      • Kaiser Permanente (NorCal) - Roseville
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Health System - Helen F. Graham Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maryland
    • Gaithersburg, Maryland, United States, 20879
      • Kaiser Permanente Mid-Atlantic
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro Minnesota Community Oncology Research Consortium
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Newtown - Cedar Crest
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Institute for Translational Oncology Research (Prisma Health)
    • Greenville, South Carolina, United States, 29607
      • St. Francis Cancer Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gunderson Lutheran Medical Center
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Hospitals and Clinicals

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 negative serum or urine pregnancy test every 3 months during the treatment period (women of childbearing potential only).
• Pathologically confirmed tumor that is metastatic, advanced, or recurrent with progression for which no alternative known to improve survival or curative therapy exists. Tumors must be TMB-H or Strata Immune Signature positive.
• Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. 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.
• Prior chemotherapy or certain immune therapies or biologic agents must have been completed at least 4 weeks (28 days) before investigational product administration and all AEs have either returned to baseline or stabilized.
• Previously treated brain or meningeal metastases with no evidence of progression by magnetic resonance imaging (MRI) for at least 4 weeks (28 days) prior to the first dose.
• 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 attenuated vaccines against infectious diseases 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 or obscure the interpretation of toxicity determination or Adverse events (AEs).
• History of myocardial infarction within 6 months or history of arterial thromboembolic event within 3 months of the first dose of investigational agent.
• 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 90 days after the last dose of investigational product.
• Any active or documented history of autoimmune disease or history of a syndrome that required systemic steroids or immunosuppressive medications.
• Any acute gastrointestinal symptoms at the time of screening or admission.
• Prior malignancy active within the previous year except for locally curable cancers that have been apparently cured.
• Prior treatment with an anti-PD-L1 or anti-PD-1 as monotherapy or in combination.
• Prior treatment with temozolomide.
• Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before investigational product administration.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TMB-H; Participants with a tumor biomarker status of TMB-H will receive zimberelimab every 3 weeks.	Drug: zimberelimab; zimberelimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1. Participants in each cohort will receive zimberelimab intravenously Q3W. Treatment will continue until progressive disease, unacceptable toxicity, withdrawal of consent, or other reasons for which investigational product discontinuation occurs.; Other Names: AB122
Experimental: Strata Immune Signature positive; Participants with a tumor biomarker status Strata Immune Signature positive will receive zimberelimab every 3 weeks.	Drug: zimberelimab; zimberelimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1. Participants in each cohort will receive zimberelimab intravenously Q3W. Treatment will continue until progressive disease, unacceptable toxicity, withdrawal of consent, or other reasons for which investigational product discontinuation occurs.; Other Names: AB122

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response Rate (ORR)	Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Tumor assessments over time will be measured using RECIST v1.1	Approximately 12 months

Secondary 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 zimberelimab with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0	From screening until 90 days after the last dose of investigational product or until initiation of a new systemic anticancer therapy, whichever occurs first, approximately 12 months
Duration of response (DoR)	The time from first documentation of disease response (CR or PR) until first documentation of progressive disease.	From the date of initiation of treatment until the date of first documented progression, through completion of the study, approximately 12 months
Time to response (TTR)	The time from treatment initiation to confirmed best overall response of CR or PR.	From the date of initiation of treatment until the date of first documented response, through completion of the study, approximately 12 months
Disease control rate at 6 months (DCR6)	Number of Participants with Complete Response, Partial Response, or Stable Disease for Greater Than 6 Months per RECIST v1.1	6 Months
Progression-free survival at 6 (PFS6)	The percentage of Participants Without Disease Progression per RECIST v1.1 and iRECIST at 6 months	6 Months
Progression-free survival at 12 months (PFS12)	The percentage of Participants Without Disease Progression per RECIST v1.1 and iRECIST at 12 months	12 Months
Overall survival at 12 months (OS12)	The percentage of participants who are alive at 12 months based on first dose to date of death.	12 Months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2019
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: September 10, 2019
• First Posted (Actual): September 12, 2019

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AB122CSP0002

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