Description:
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)
Title
- Brief Title: Study of AMG 910 in Subjects With CLDN18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
20180292
- NCT ID:
NCT04260191
Conditions
- Gastric and Gastroesophageal Junction Adenocarcinoma
Interventions
Drug | Synonyms | Arms |
---|
AMG 910 | | Dose-expansion |
Purpose
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)
Trial Arms
Name | Type | Description | Interventions |
---|
Dose-exploration | Experimental | 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. | |
Dose-expansion | Experimental | 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. | |
Eligibility Criteria
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).
- 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.
Exclusion Criteria:
- Any anticancer therapy or immunotherapy within 4 weeks of start of first dose.
- 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.
Maximum Eligible Age: | 99 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with dose-limiting toxicities (DLT) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | 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 |
Secondary Outcome Measures
Measure: | Maximum serum concentration (Cmax) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Minimum serum concentration (Cmin) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Area under the concentration-time curve (AUC) over the dosing interval |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | AUC accumulation following multiple dosing |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Half-life (t1/2) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Duration of response (DOR) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Time to progression |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Progression-free survival (PFS) |
Time Frame: | 6 months and 1 year |
Safety Issue: | |
Description: | |
Measure: | Overall survival (OS) |
Time Frame: | 1 year and 2 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Amgen |
Last Updated
February 5, 2020