Clinical trial NCT04117958: Study of AMG 199 in Subjects With MUC17-Positive Solid Tumors Including Gastric, Gastroesophageal Junction, Colorectal, and Pancreatic Cancers
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: MUC17-positive Solid Tumors
Keywords: Gastric Cancer
Gastroesophageal Junction Cancer
Colorectal Cancer
Pancreatic Cancer
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2019-10-07
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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.

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 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.

Primary outcomes:
measure: Incidence of Dose-limiting toxicities (DLT)
timeFrame: 3 years
measure: Incidence of Treatment-emergent adverse events (TEAEs)
timeFrame: 3 years
measure: Incidence of Treatment-related adverse events (TRAEs)
timeFrame: 3 years
measure: Number of subjects with changes in vital signs
timeFrame: 3 years
measure: Number of subjects with changes in clinical laboratory tests
timeFrame: 3 years
measure: Number of subjects with changes in electrocardiogram (ECG)
timeFrame: 3 years
Secondary outcomes:
measure: Maximum serum concentration (Cmax) of AMG 199
timeFrame: 3 years
measure: Minimum serum concentration (Cmin) of AMG 199
timeFrame: 3 years
measure: Area under the concentration-time curve (AUC) of AMG 199
timeFrame: 3 years
measure: Accumulation following multiple dosing of AMG 199
timeFrame: 3 years
measure: Half-life (t1/2) of AMG 199
timeFrame: 3 years
measure: Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST.
timeFrame: 3 years
measure: Duration of response (DOR).
timeFrame: 3 years
measure: Time to progression (TTP)
timeFrame: 3 years
measure: Progression-free survival (PFS), 6-month PFS
timeFrame: 6 months
measure: Progression-free survival (PFS), 1-year PFS
timeFrame: 1 year
measure: Overall survival (OS), 1-year OS.
timeFrame: 1 year
measure: Overall survival (OS), 2-year OS
timeFrame: 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Orange
country: United States
facility: University of California at Irvine Medical Center
state: California
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg Eppendorf Onkologisches Zentrum
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen Campus Grosshadern
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - location VUmc
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
state: Comunidad Valenciana
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: