Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers (ARC-25)

A Phase 1/1b Study to Evaluate the Safety and Tolerability of AB598 Monotherapy and Combination Therapy in Participants With Advanced Malignancies

The primary purpose of this study is to assess the safety and tolerability of AB598 in participants with advanced malignancies.

Study Overview

• Status: Active, not recruiting
• Conditions: Cervical Cancer; Gastric Cancer; Esophageal Cancer; Ovarian Cancer; Bladder Cancer; Advanced Cancer; Non-Small Cell Lung Cancer (NSCLC); Advanced Malignancies; Renal Cell Carcinoma (RCC); Triple Negative Breast Cancer (TNBC); Head and Neck Squamous Cell Carcinoma (HNSCC); Gastroesophageal-junction Cancer (GEJ)
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Zimberelimab; Drug: Fluorouracil; Drug: Leucovorin; Drug: AB598

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Research Site
• Taiwan
  • Tainan, Taiwan
    • Research Site
  • Taipei, Taiwan
    • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Research Site
    • Lake City, Florida, United States, 32024
      • Research Site
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Research Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Research Site
    • Cleveland, Ohio, United States, 44106
      • Research Site
  • Texas
    • Irving, Texas, United States, 75039
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) guidance
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Prior systemic radiation or whole brain radiation therapy must have been completed at least 4 weeks before investigational product (IP) administration. Other palliative radiotherapy must be completed 2 weeks before investigational product administration, if radiation therapy-related AEs have resolved to Grade ≤ 1.

• Monotherapy-specific criteria for dose escalation and PD cohorts:

  • Dose Escalation: Participants may have any pathologically confirmed advanced or metastatic solid tumor for which standard therapy has proven ineffective, intolerable, or is considered inappropriate.
  • Pharmacodynamic Cohorts: Participants may have any pathologically confirmed advanced or metastatic solid tumors for which standard therapy has proven ineffective, intolerable, or is considered inappropriate. Participants must be able to undergo collection of a fresh frozen biopsy during screening, as well as provide an on-treatment fresh frozen biopsy.

• Dose Expansion cohort criteria:

  • Histologically confirmed, documented diagnosis of HER2-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.
  • No prior systemic treatment for locally advanced unresectable or metastatic disease.
  • Cannot have progressed within 6 months of prior platinum-based chemotherapy for earlier stage disease.

Key Exclusion Criteria:

• Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of study
• Underlying medical conditions or AEs that, in the investigator or sponsor's opinion, will make the administration of the study drugs hazardous
• Any active or documented history of autoimmune disease including but not limited to inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, within 3 years of the first dose of study treatment
• History of trauma or major surgery within 28 days prior to the first dose of study drug
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment with certain protocol specified exceptions

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Cohort 1; Participants will receive AB598 intravenous (IV) infusion once every 3 weeks	Drug: AB598; Administered as specified in the treatment arm
Experimental: Dose Escalation Cohort 2; Participants will receive AB598 IV infusion once every 3 weeks	Drug: AB598; Administered as specified in the treatment arm
Experimental: Dose Escalation Cohort 3; Participants will receive AB598 IV infusion once every 3 weeks	Drug: AB598; Administered as specified in the treatment arm
Experimental: Dose Escalation Cohort 4; Participants will receive AB598 IV infusion once every 3 weeks	Drug: AB598; Administered as specified in the treatment arm
Experimental: Pharmacodynamic Cohort 1; Participants will receive AB598 IV infusion once every 3 weeks	Drug: AB598; Administered as specified in the treatment arm
Experimental: Pharmacodynamic Cohort 2; Participants will receive AB598 IV infusion once every 3 weeks	Drug: AB598; Administered as specified in the treatment arm
Experimental: Pharmacodynamic Cohort 3; Participants will receive AB598 IV infusion once every 3 weeks	Drug: AB598; Administered as specified in the treatment arm
Experimental: Dose Expansion Gastric/GEJ Cancer (phase 1b); Participants will receive AB598 IV infusion every 2 weeks in combination with zimberelimab and FOLFOX (oxaliplatin, leucovorin, fluorouracil)	Drug: Oxaliplatin; Administered as specified in the treatment arm; Drug: Zimberelimab; Administered as specified in the treatment arm; Other Names: AB122; Drug: Fluorouracil; Administered as specified in the treatment arm; Drug: Leucovorin; Administered as specified in the treatment arm; Drug: AB598; Administered as specified in the treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to 2 years
Dose Escalation Cohorts: Number of Participants with Dose-Limiting Toxicities (DLTs)	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	Up to 2 years
Number of Participants Who Test Positive for Antidrug Antibodies (ADAs) to AB598	Up to 2 years
Area Under the Concentration-Time Curve from Administration ("0") to the Time That the Drug is No Longer Present in the Body ("infinity") (AUC 0-inf) in Whole Blood and Plasma	Predose, Up to 4 hours post dose
Maximum Concentration (Cmax) in Whole Blood and Plasma	Predose, Up to 4 hours post dose
Time to Maximum Concentration (Tmax) in Whole Blood and Plasma	Predose, Up to 4 hours post dose
Dose Expansion Cohort: Duration of Response (DOR)	Up to 2 years

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• ARC-25 - Public website

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: May 26, 2023
• First Submitted That Met QC Criteria: May 26, 2023
• First Posted (Actual): June 6, 2023

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Zimberelimab; AB122; AB598
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Esophageal Diseases; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Urologic Neoplasms; Carcinoma; Uterine Cervical Diseases; Kidney Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Urinary Bladder Diseases; Carcinoma, Squamous Cell; Breast Neoplasms; Skin and Connective Tissue Diseases; Squamous Cell Carcinoma of Head and Neck; Stomach Neoplasms; Esophageal Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Uterine Cervical Neoplasms; Urinary Bladder Neoplasms; Triple Negative Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzymes and Coenzymes; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Fluorouracil; Leucovorin; zimberelimab
• Other Study ID Numbers: ARC-25

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