- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04117958
Study of AMG 199 in Subjects With MUC17-Positive Solid Tumors Including Gastric, Gastroesophageal Junction, Colorectal, and Pancreatic Cancers
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 Solid Tumors Including Gastric, Gastroesophageal Junction, Colorectal, and Pancreatic Cancers
Study Overview
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 solid tumors including gastric cancer, gastroesophageal junction (GEJ), colorectal, and pancreatic cancers, collectively referred to as "solid tumors" in this clinical investigation 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Salzburg, Austria, 5020
- Landeskrankenhaus Salzburg
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Villejuif, France, 94805
- Institut Gustave Roussy
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Hamburg, Germany, 20246
- Universitaetsklinikum Hamburg Eppendorf Onkologisches Zentrum
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Leipzig, Germany, 04103
- Universitaetsklinikum Leipzig
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Muenchen, Germany, 81675
- Klinikum Rechts der Isar
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Muenchen, Germany, 81377
- Klinikum der Universitaet Muenchen Campus Grosshadern
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Aichi
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Nagoya-shi, Aichi, Japan, 464-8681
- Aichi Cancer Center
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Chiba
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Kashiwa-shi, Chiba, Japan, 277-8577
- National Cancer Center Hospital East
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Tokyo
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Chuo-ku, Tokyo, Japan, 104-0045
- National Cancer Center Hospital
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Seoul, Korea, Republic of, 138-736
- Asan Medical Center
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Seoul, Korea, Republic of, 03080
- Seoul National University Hospital
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Seoul, Korea, Republic of, 03722
- Severance Hospital Yonsei University Health System
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Amsterdam, Netherlands, 1081 HV
- Amsterdam UMC - location VUmc
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Leiden, Netherlands, 2333 ZA
- Leids Universitair Medisch Centrum
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Cataluña
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Barcelona, Cataluña, Spain, 08035
- Hospital Universitari Vall D Hebron
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Comunidad Valenciana
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Valencia, Comunidad Valenciana, Spain, 46010
- Hospital Clínico Universitario de Valencia
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Taipei, Taiwan, 10002
- National Taiwan University Hospital
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Taipei, Taiwan, 11217
- Taipei Veterans General Hospital
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California
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Duarte, California, United States, 91010
- City of Hope National Medical Center
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Orange, California, United States, 92868
- University of California at Irvine Medical Center
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North Carolina
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Health Sciences
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 have been refractory to or have relapsed after two or more prior lines of standard systemic therapy that included a platinum, a fluoropyrimidine, nivolumab (in combination with a platinum and a fluoropyrimidine), either a taxane or irinotecan, and an approved vascular endothelial growth factor receptor (VEGFR) antibody/tyrosine kinase inhibitor (TKI).
OR
• Subjects with histologically or cytologically confirmed metastatic or locally advanced unresectable colorectal cancer positive for MUC17. Subjects should have been refractory to or have relapsed after at least two and up to five prior lines of standard systemic therapy. Therapy should have included an approved vascular endothelial growth factor (VEGF) antibody (if clinically appropriate) and epidermal growth factor receptor (EGFR) antibody (if kirsten rat sarcoma [KRAS]/ neuroblastoma RAS viral oncogene homolog [NRAS]/ v-Raf murine sarcoma viral oncogene homolog B1 [BRAF] wild type tumor).
OR
- Subjects with histologically or cytologically confirmed unresectable or metastatic pancreatic ductal adenocarcinoma positive for MUC17. Subjects should have been refractory to or have relapsed after at least one and up to three prior lines of standard systemic therapy.
- Gastric adenocarcinoma and GEJ adenocarcinoma: Subjects eligible for human epidermal growth factor receptor 2 (HER2) directed therapy, prior systemic therapy should have an approved HER2 targeting antibody approved for treatment of gastric cancer. For subjects with microsatellite instability high (MSI H) or mismatch repair deficient (dMMR) tumors a prior line of treatment should have included an approved programmed cell death protein-1 (PD-1) blocking antibody.
OR
- Colorectal cancer: For subjects with MSI H or dMMR tumors a prior line of treatment should have included an approved PD-1-blocking antibody. For subjects with BRAF V600E mutation positive tumors a prior line of treatment should have included a BRAF inhibitor.
- 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 solid tumors were medically not appropriate should be documented in the subject's electronic case report form (eCRF). Subjects may also be included if the aforementioned therapeutic options have not been available or accessible for them.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Dose-exploration phase
The 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.
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AMG 199 is a BiTE® molecule designed to direct T cells towards MUC17-expressing cells.
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Experimental: Dose-expansion phase
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.
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AMG 199 is a BiTE® molecule designed to direct T cells towards MUC17-expressing cells.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence of Dose-limiting toxicities (DLT)
Time Frame: 3 years
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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).
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3 years
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Incidence of Treatment-emergent adverse events (TEAEs)
Time Frame: 3 years
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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).
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3 years
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Incidence of Treatment-related adverse events (TRAEs)
Time Frame: 3 years
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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).
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3 years
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Number of subjects with changes in vital signs
Time Frame: 3 years
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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).
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3 years
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Number of subjects with changes in clinical laboratory tests
Time Frame: 3 years
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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).
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3 years
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Number of subjects with changes in electrocardiogram (ECG)
Time Frame: 3 years
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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).
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3 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Maximum serum concentration (Cmax) of AMG 199
Time Frame: 3 years
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To characterize the PK (Pharmacokinetics) of AMG 199.
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3 years
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Minimum serum concentration (Cmin) of AMG 199
Time Frame: 3 years
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To characterize the PK (Pharmacokinetics) of AMG 199.
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3 years
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Area under the concentration-time curve (AUC) of AMG 199
Time Frame: 3 years
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To characterize the PK (Pharmacokinetics) of AMG 199.
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3 years
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Accumulation following multiple dosing of AMG 199
Time Frame: 3 years
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To characterize the PK (Pharmacokinetics) of AMG 199.
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3 years
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Half-life (t1/2) of AMG 199
Time Frame: 3 years
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To characterize the PK (Pharmacokinetics) of AMG 199.
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3 years
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Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST.
Time Frame: 3 years
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To evaluate preliminary anti-tumor activity of AMG 199
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3 years
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Duration of response (DOR).
Time Frame: 3 years
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To evaluate preliminary anti-tumor activity of AMG 199
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3 years
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Time to progression (TTP)
Time Frame: 3 years
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To evaluate preliminary anti-tumor activity of AMG 199
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3 years
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Progression-free survival (PFS), 6-month PFS
Time Frame: 6 months
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To evaluate preliminary anti-tumor activity of AMG 199
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6 months
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Progression-free survival (PFS), 1-year PFS
Time Frame: 1 year
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To evaluate preliminary anti-tumor activity of AMG 199
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1 year
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Overall survival (OS), 1-year OS.
Time Frame: 1 year
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To evaluate preliminary anti-tumor activity of AMG 199
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1 year
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Overall survival (OS), 2-year OS
Time Frame: 2 years
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To evaluate preliminary anti-tumor activity of AMG 199
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2 years
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: MD, Amgen
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20180290
- 2019-002708-42 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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