MUC17-positive Solid Tumors
Conditions
Keywords
Gastric Cancer, Gastroesophageal Junction Cancer, Colorectal Cancer, Pancreatic Cancer
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.
Interventions
DRUGAMG 199
AMG 199 is a BiTE® molecule designed to direct T cells towards MUC17-expressing cells.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with changes in vital signs | 3 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). |
| Number of subjects with changes in clinical laboratory tests | 3 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). |
| Incidence of Dose-limiting toxicities (DLT) | 3 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). |
| Incidence of Treatment-emergent adverse events (TEAEs) | 3 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). |
| Incidence of Treatment-related adverse events (TRAEs) | 3 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). |
| Number of subjects with changes in electrocardiogram (ECG) | 3 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
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DOR). | 3 years | To evaluate preliminary anti-tumor activity of AMG 199 |
| Time to progression (TTP) | 3 years | To evaluate preliminary anti-tumor activity of AMG 199 |
| Progression-free survival (PFS), 6-month PFS | 6 months | To evaluate preliminary anti-tumor activity of AMG 199 |
| Maximum serum concentration (Cmax) of AMG 199 | 3 years | To characterize the PK (Pharmacokinetics) of AMG 199. |
| Overall survival (OS), 1-year OS. | 1 year | To evaluate preliminary anti-tumor activity of AMG 199 |
| Overall survival (OS), 2-year OS | 2 years | To evaluate preliminary anti-tumor activity of AMG 199 |
| Progression-free survival (PFS), 1-year PFS | 1 year | To evaluate preliminary anti-tumor activity of AMG 199 |
| Minimum serum concentration (Cmin) of AMG 199 | 3 years | To characterize the PK (Pharmacokinetics) of AMG 199. |
| Area under the concentration-time curve (AUC) of AMG 199 | 3 years | To characterize the PK (Pharmacokinetics) of AMG 199. |
| Accumulation following multiple dosing of AMG 199 | 3 years | To characterize the PK (Pharmacokinetics) of AMG 199. |
| Half-life (t1/2) of AMG 199 | 3 years | To characterize the PK (Pharmacokinetics) of AMG 199. |
| Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST. | 3 years | To evaluate preliminary anti-tumor activity of AMG 199 |
Countries
Austria, France, Germany, Japan, Netherlands, South Korea, Spain, Taiwan, United States
Outcome results
None listed