Clinical Trials /

Study of AMG 199 in Subjects With MUC17-Positive Gastric and Gastroesophageal Junction Cancer

NCT04117958

Description:

To evaluate the safety and tolerability of AMG 199 in adult subjects with MUC17-positive gastric and gastroesophageal junction cancer 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:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of AMG 199 in Subjects With MUC17-Positive Gastric and Gastroesophageal Junction Cancer
  • Official Title: A Global Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of the Half-life Extended Bispecific T-cell Engager AMG 199 in Subjects With MUC17-Positive Gastric and Gastroesophageal Junction Cancer

Clinical Trial IDs

  • ORG STUDY ID: 20180290
  • SECONDARY ID: 2019-002708-42
  • NCT ID: NCT04117958

Conditions

  • Gastric and Gastroesophageal Junction Cancer

Interventions

DrugSynonymsArms
AMG 199Dose-expansion phase

Purpose

To evaluate the safety and tolerability of AMG 199 in adult subjects with MUC17-positive gastric and gastroesophageal junction cancer and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).

Detailed Description

      AMG 199 is a novel half-life extended (HLE) bispecific T cell engager (BiTE®) molecule
      designed to direct T cells towards MUC17-expressing cells. This is a first-in-human study in
      adult subjects with MUC17-positive gastric cancer or gastroesophageal junction (GEJ) cancer,
      to assess AMG 199 safety, tolerability, pharmacokinetics (PK), and anti-tumor activity, with
      additional exploratory objectives to assess pharmacodynamics (PD), correlative biomarker
      analysis, and immunogenicity.

      The primary end point is to evaluate the safety and tolerability of AMG 199 in adult
      subjects, and determine the MTD and RP2D. The secondary end point is characterize the PK and
      anti-tumor activity of AMG 199.
    

Trial Arms

NameTypeDescriptionInterventions
Dose-exploration phaseExperimentalThe dose-exploration phase of the study will estimate the MTD (Maximum Tolerated Dose) of AMG 199 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 199
Dose-expansion phaseExperimentalThe 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 199

Eligibility Criteria

        Inclusion Criteria:

        Key Inclusion Criteria:

          -  Subjects with histologically or cytologically confirmed metastatic or locally advanced
             unresectable gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma
             positive for MUC17. 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 one measurable lesion ≥ 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:

        Key Exclusion Criteria:

          -  Any anticancer therapy or immunotherapy within 4 weeks of start of first dose.

          -  Central nervous system (CNS) metastases, leptomeningeal, or spinal cord compression.

          -  Autoimmune disorders requiring chronic systemic steroid therapy or any other form of
             immunosuppressive therapy. Subjects may be included if the treatment is discontinued
             more than 3 months prior to the first dose of AMG 199, there is a low likelihood of
             relapse from the autoimmune disorder, AND there is agreement between the investigator
             and the Amgen Medical Monitor.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Dose-limiting toxicities (DLT)
Time Frame:2 years
Safety Issue:
Description:To evaluate the safety and tolerability of AMG 199 in adult subjects and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).

Secondary Outcome Measures

Measure:Maximum serum concentration (Cmax) of AMG 199
Time Frame:2 years
Safety Issue:
Description:To characterize the PK (Pharmacokinetics) of AMG 199.
Measure:Minimum serum concentration (Cmax) of AMG 199
Time Frame:2 years
Safety Issue:
Description:To characterize the PK (Pharmacokinetics) of AMG 199.
Measure:Area under the concentration-time curve (AUC) of AMG 199
Time Frame:2 years
Safety Issue:
Description:To characterize the PK (Pharmacokinetics) of AMG 199.
Measure:Accumulation following multiple dosing of AMG 199
Time Frame:2 years
Safety Issue:
Description:To characterize the PK (Pharmacokinetics) of AMG 199.
Measure:Half-life (t1/2) of AMG 199
Time Frame:2 years
Safety Issue:
Description:To characterize the PK (Pharmacokinetics) of AMG 199.
Measure:Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST.
Time Frame:2 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 199
Measure:Duration of response (DOR).
Time Frame:2 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 199
Measure:Time to progression (TTP)
Time Frame:2 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 199
Measure:Progression-free survival (PFS), 6-month PFS
Time Frame:6 months
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 199
Measure:Progression-free survival (PFS), 1-year PFS
Time Frame:1 year
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 199
Measure:Overall survival (OS), 1-year OS.
Time Frame:1 year
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 199
Measure:Overall survival (OS), 2-year OS
Time Frame:2 years
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of AMG 199

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Last Updated

December 1, 2020