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

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.

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.

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