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)
- 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
- Subjects should be able to use proton pump inhibitors.
- 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
- 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.