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Study of AMG 199 in Subjects With MUC17-Positive Solid Tumors Including Gastric, Gastroesophageal Junction, Colorectal, and Pancreatic Cancers

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ClinicalTrials.gov Identifier: NCT04117958
Recruitment Status : Recruiting
First Posted : October 7, 2019
Last Update Posted : October 21, 2021
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
MUC17-positive Solid Tumors Drug: AMG 199 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Solid Tumors Including Gastric, Gastroesophageal Junction, Colorectal, and Pancreatic Cancers
Actual Study Start Date : January 20, 2020
Estimated Primary Completion Date : April 13, 2025
Estimated Study Completion Date : April 13, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: AMG 199
AMG 199 is a BiTE® molecule designed to direct T cells towards MUC17-expressing cells.

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.
Drug: AMG 199
AMG 199 is a BiTE® molecule designed to direct T cells towards MUC17-expressing cells.




Primary Outcome Measures :
  1. Incidence of Dose-limiting toxicities (DLT) [ Time Frame: 2 years ]
    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).

  2. Incidence of Treatment-emergent adverse events (TEAEs) [ Time Frame: 2 years ]
    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).

  3. Incidence of Treatment-related adverse events (TRAEs) [ Time Frame: 2 years ]
    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).

  4. Number of subjects with changes in vital signs [ Time Frame: 2 years ]
    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).

  5. Number of subjects with changes in clinical laboratory tests [ Time Frame: 2 years ]
    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).

  6. Number of subjects with changes in electrocardiogram (ECG) [ Time Frame: 2 years ]
    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 :
  1. Maximum serum concentration (Cmax) of AMG 199 [ Time Frame: 2 years ]
    To characterize the PK (Pharmacokinetics) of AMG 199.

  2. Minimum serum concentration (Cmin) of AMG 199 [ Time Frame: 2 years ]
    To characterize the PK (Pharmacokinetics) of AMG 199.

  3. Area under the concentration-time curve (AUC) of AMG 199 [ Time Frame: 2 years ]
    To characterize the PK (Pharmacokinetics) of AMG 199.

  4. Accumulation following multiple dosing of AMG 199 [ Time Frame: 2 years ]
    To characterize the PK (Pharmacokinetics) of AMG 199.

  5. Half-life (t1/2) of AMG 199 [ Time Frame: 2 years ]
    To characterize the PK (Pharmacokinetics) of AMG 199.

  6. Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST. [ Time Frame: 2 years ]
    To evaluate preliminary anti-tumor activity of AMG 199

  7. Duration of response (DOR). [ Time Frame: 2 years ]
    To evaluate preliminary anti-tumor activity of AMG 199

  8. Time to progression (TTP) [ Time Frame: 2 years ]
    To evaluate preliminary anti-tumor activity of AMG 199

  9. Progression-free survival (PFS), 6-month PFS [ Time Frame: 6 months ]
    To evaluate preliminary anti-tumor activity of AMG 199

  10. Progression-free survival (PFS), 1-year PFS [ Time Frame: 1 year ]
    To evaluate preliminary anti-tumor activity of AMG 199

  11. Overall survival (OS), 1-year OS. [ Time Frame: 1 year ]
    To evaluate preliminary anti-tumor activity of AMG 199

  12. Overall survival (OS), 2-year OS [ Time Frame: 2 years ]
    To evaluate preliminary anti-tumor activity of AMG 199



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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).
  • 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).
  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04117958


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT04117958    
Other Study ID Numbers: 20180290
2019-002708-42 ( EudraCT Number )
First Posted: October 7, 2019    Key Record Dates
Last Update Posted: October 21, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
URL: http://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Gastric Cancer
Gastroesophageal Junction Cancer
Colorectal Cancer
Pancreatic Cancer
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases