Study Of AMG 199 In Subjects With MUC17-Positive Solid Tumors Including Gastric, Gastroesophageal Junction, Colorectal, And Pancreatic Cancers

Study Overview

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

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).

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.

MUC17-positive Solid Tumors

DRUG: AMG 199

20180290
2019-002708-42 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-10-04	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-11-20
First Submitted that Met QC Criteria 2019-10-04	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-11-22
First Posted (ACTUAL) 2019-10-07	Results First Posted N/A	Last Verified 2024-11

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/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 (Pharmacody	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.

Participant Group/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 (Pharmacody

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	Measure Description	Time Frame
Incidence of Dose-limiting toxicities (DLT)	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 years
Incidence of Treatment-emergent adverse events (TEAEs)	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 years
Incidence of Treatment-related adverse events (TRAEs)	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 years
Number of subjects with changes in vital signs	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 years
Number of subjects with changes in clinical laboratory tests	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 years
Number of subjects with changes in electrocardiogram (ECG)	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 years

Secondary Outcome Measures	Measure Description	Time Frame
Maximum serum concentration (Cmax) of AMG 199	To characterize the PK (Pharmacokinetics) of AMG 199.	3 years
Minimum serum concentration (Cmin) of AMG 199	To characterize the PK (Pharmacokinetics) of AMG 199.	3 years
Area under the concentration-time curve (AUC) of AMG 199	To characterize the PK (Pharmacokinetics) of AMG 199.	3 years
Accumulation following multiple dosing of AMG 199	To characterize the PK (Pharmacokinetics) of AMG 199.	3 years
Half-life (t1/2) of AMG 199	To characterize the PK (Pharmacokinetics) of AMG 199.	3 years
Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST.	To evaluate preliminary anti-tumor activity of AMG 199	3 years
Duration of response (DOR).	To evaluate preliminary anti-tumor activity of AMG 199	3 years
Time to progression (TTP)	To evaluate preliminary anti-tumor activity of AMG 199	3 years
Progression-free survival (PFS), 6-month PFS	To evaluate preliminary anti-tumor activity of AMG 199	6 months
Progression-free survival (PFS), 1-year PFS	To evaluate preliminary anti-tumor activity of AMG 199	1 year
Overall survival (OS), 1-year OS.	To evaluate preliminary anti-tumor activity of AMG 199	1 year
Overall survival (OS), 2-year OS	To evaluate preliminary anti-tumor activity of AMG 199	2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: MD, Amgen

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record