Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers

Phase 1

Recruiting

• Conditions: Bladder Cancer; Advanced Malignancies; Head and Neck Squamous Cell Carcinoma (HNSCC); Advanced Cancer; Esophageal Cancer; Gastric Cancer; Non-Small Cell Lung Cancer (NSCLC); Ovarian Cancer; Renal Cell Carcinoma (RCC); Triple Negative Breast Cancer (TNBC)
• Interventions: Drug: AB598; Drug: Zimberelimab; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin

• Registration Number: NCT05891171
• Lead Sponsor: Arcus Biosciences, Inc.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-26
• Study First Submitted QC: 2023-05-26
• Study First Posted: 2023-06-06
• Study Start: 2023-10-13
• Status Verified: 2024-05
• Last Update Submitted: 2025-04-25
• Last Update Posted: 2025-04-29
• Primary Completion: 2026-03
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 87

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation Cohort 1	AB598	Participants will receive AB598 intravenous (IV) infusion once every 3 weeks
Dose Escalation Cohort 2	AB598	Participants will receive AB598 IV infusion once every 3 weeks
Dose Escalation Cohort 3	AB598	Participants will receive AB598 IV infusion once every 3 weeks
Dose Escalation Cohort 4	AB598	Participants will receive AB598 IV infusion once every 3 weeks
Pharmacodynamic Cohort 1	AB598	Participants will receive AB598 IV infusion once every 3 weeks
Pharmacodynamic Cohort 2	AB598	Participants will receive AB598 IV infusion once every 3 weeks
Pharmacodynamic Cohort 3	AB598	Participants will receive AB598 IV infusion once every 3 weeks
Dose Expansion Gastric/GEJ Cancer (phase 1b)	AB598	Participants will receive AB598 IV infusion every 2 weeks in combination with zimberelimab and FOLFOX (oxaliplatin, leucovorin, fluorouracil)
Dose Expansion Gastric/GEJ Cancer (phase 1b)	Zimberelimab	Participants will receive AB598 IV infusion every 2 weeks in combination with zimberelimab and FOLFOX (oxaliplatin, leucovorin, fluorouracil)
Dose Expansion Gastric/GEJ Cancer (phase 1b)	Fluorouracil	Participants will receive AB598 IV infusion every 2 weeks in combination with zimberelimab and FOLFOX (oxaliplatin, leucovorin, fluorouracil)
Dose Expansion Gastric/GEJ Cancer (phase 1b)	Leucovorin	Participants will receive AB598 IV infusion every 2 weeks in combination with zimberelimab and FOLFOX (oxaliplatin, leucovorin, fluorouracil)
Dose Expansion Gastric/GEJ Cancer (phase 1b)	Oxaliplatin	Participants will receive AB598 IV infusion every 2 weeks in combination with zimberelimab and FOLFOX (oxaliplatin, leucovorin, fluorouracil)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Number of Participants Who Test Positive for Antidrug Antibodies (ADAs) to AB598	Up to 2 years
Objective Response Rate (ORR)	Up to 2 years
Dose Expansion Cohort: Duration of Response (DOR)	Up to 2 years

Trial Locations

Locations (20)

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung City, Taiwan

Mayo Clinic Arizona; 🇺🇸 Phoenix, Arizona, United States

Ronald Reagan UCLA Medical Center; 🇺🇸 Santa Monica, California, United States

Providence Medical Group Santa Rosa - Cancer Center; 🇺🇸 Santa Rosa, California, United States

Mayo Clinic Florida; 🇺🇸 Jacksonville, Florida, United States

Lake City Cancer Care, LLC.; 🇺🇸 Lake City, Florida, United States

Affinity Health Hope and Healing Cancer Services, LLC; 🇺🇸 Hinsdale, Illinois, United States

Goshen Center for Cancer Care; 🇺🇸 Goshen, Indiana, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Gabrail Cancer Center (GCC) Canton Facility; 🇺🇸 Canton, Ohio, United States

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

Next Oncology Dallas; 🇺🇸 Irving, Texas, United States

Next Oncology Virginia; 🇺🇸 Fairfax, Virginia, United States

Adelaide Cancer Research; 🇦🇺 Adelaide, Australia

Queen Elizabeth Hospital; 🇦🇺 Adelaide, Australia

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Linkou Branch Chang Gung Memorial Hospital; 🇨🇳 Taoyuan City, Taiwan