Clinical Trials /

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

NCT04260191

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)

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
AMG 910Dose-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

NameTypeDescriptionInterventions
Dose-explorationExperimentalThe 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.
  • AMG 910
Dose-expansionExperimentalThe 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.
  • AMG 910

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