Study of AMG 910 in Subjects With CLDN18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma

A Global Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of the Half-life Extended Bispecific T-cell Engager AMG 910 in Subjects With Claudin 18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma

To evaluate the safety and tolerability of AMG 910 in adult subjects, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)

Inclusion Criteria:

• Subjects with histologically or cytologically confirmed metastatic or locally advanced unresectable gastric or GEJ adenocarcinoma positive for CLDN18.2.
• Subjects should not be eligible for curative surgery and should have been refractory to or have relapsed after two or more prior lines of standard systemic therapy that included a platinum, a fluoropyrimidine, either a taxane or irinotecan, and an approved vascular endothelial growth factor receptor (VEGFR) antibody/tyrosine kinase inhibitor (TKI) and depending on country-specific standards and approvals.
• For subjects eligible for human epidermal growth factor receptor 2 (HER2) directed therapy, prior systemic therapy should have included a HER2 targeting antibody approved for treatment of gastric cancer.
• Subjects may also be included if the aforementioned therapeutic options were medically not appropriate for them. In these cases, the reason(s) why required prior therapies for gastric cancer were medically not appropriate should be documented in the subject's electronic case report form (eCRF).
• For dose-expansion only: Subjects with at least 1 measurable lesion greater than or equal to 10mm which has not undergone biopsy within 3 months of screening scan. This lesion cannot be biopsied at any time during the study.
• Subjects with stable condition and anti-coagulative therapy ongoing for at least 1 month, no obvious signs and symptoms of bleeding, and coagulation parameters are fulfilled.
• Subjects should be able to use proton pump inhibitors.

Exclusion Criteria:

• Any anticancer therapy or immunotherapy within 4 weeks of start of first dose (14 days for palliative radiation).
• Untreated or symptomatic central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
• Autoimmune disorders requiring chronic systemic steroid therapy or any other form of immunosuppressive therapy while on study, eg, ulcerative colitis, Crohn's disease, or any other gastrointestinal autoimmune disorder causing chronic nausea, vomiting, or diarrhea. Recent or current use of inhaled steroids or physiological substitution in case of adrenal insufficiency is not exclusionary.
• Evidence or history within last 3 months of gastrointestinal inflammatory conditions not associated with the underlying cancer disease including gastrinomas, duodenitis, proven gastric ulcer, duodenal ulcer, pancreatitis, or subjects with recent gastric bleeding. Subjects may be included if the symptomatic/immunosuppressive treatment is discontinued more than 4 weeks prior to the first dose of AMG 910, symptoms have resolved, and gastroscopy does not indicate signs of active disease.
• Subjects with inherited bleeding disorders (eg, Willebrand's disease, hemophilia A and other clotting factor deficiency) and subjects with known heparin-induced thrombocytopenia.
• Subjects requiring non-steroidal anti-inflammatory drugs (NSAIDs) during study treatment. The NSAID(s) should be stopped within 7 days prior to start of treatment.