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

Study Overview
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Brief Summary
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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)

Official Title
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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

Conditions
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Gastric and Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
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* Drug: AMG 910


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-exploration<br>The dose-exploration phase of the study will estimate the MTD (Maximum Tolerated Dose) of AMG 910 using a Bayesian logistic regression model (BLRM). A RP2D (Recommended Phase 2 Dose) may be identified based on emerging safety, efficacy, and PD (Pharmacodynamics) data prior to reaching an MTD. Alternative dosing schedule(s) may be explored based on emerging PK (Pharmacokinetics) and safety data. | Drug: AMG 910<br>* Dose Exploration Dose Expansion<br>|
| Experimental: Dose-expansion<br>The dose-expansion phase will be conducted to confirm safety, PK, and PD at the MTD or RP2D and to obtain further safety and efficacy data and enable correlative biomarker analysis. | Drug: AMG 910<br>* Dose Exploration Dose Expansion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose-limiting toxicities (DLT) | Subject grade of dose limiting toxicities is the occurrence of any of the toxicities during the DLT evaluation period if judged by the investigator to be related to the administration of AMG 910 | 2 years | 
| Number of participants with treatment-emergent adverse events |  | 2 years | 
| Number of participants with treatment-related adverse events |  | 2 years | 
| Number of participants with clinically significant changes in vital signs |  | 2 years | 
| Number of participants with clinically significant changes in electrocardiogram (ECG) |  | 2 years | 
| Number of participants with clinically significant changes in clinical laboratory tests |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum serum concentration (Cmax) |  | 2 years | 
| Minimum serum concentration (Cmin) |  | 2 years | 
| Area under the concentration-time curve (AUC) over the dosing interval |  | 2 years | 
| AUC accumulation following multiple dosing |  | 2 years | 
| Half-life (t1/2) |  | 2 years | 
| Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST |  | 2 years | 
| Duration of response (DOR) |  | 2 years | 
| Time to progression |  | 2 years | 
| Progression-free survival (PFS) |  | 6 months and 1 year | 
| Overall survival (OS) |  | 1 year and 2 years |