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
- Conditions
- maagkanker, kanker van de maag-slokdarmovergang, darm- en pancreaskankercancer of stomachstomach cancer1001799010017991
- Registration Number
- NL-OMON56431
- Lead Sponsor
- Amgen
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
103 - Subjects with histologically or cytologically confirmed metastatic or
locally advanced gastric adenocarcinoma or GEJ adenocarcinoma positive for
MUC17 as defined by the test described herein. 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 CRC positive for MUC17 as defined by the test
described herein. 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 as defined by
the test described herein. Subjects should have been refractory to or have
relapsed after at least one and up to three prior lines of standard systemic
therapy.
104 - Gastric adenocarcinoma and GEJ adenocarcinoma: Subjects eligible for
human epidermal growth factor receptor 2 (HER2) directed therapy, prior
systemic therapy should have included a 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 PD-1-blocking antibody.
105 - Subjects may also be included if the aforementioned therapeutic options
were medically not appropriate for them.
106 - 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.
Refer to section 5.1 of the protocol.
• 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.
Refer to 5.2 of the protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary study parameters/outcome of the study:<br /><br>• Dose-limiting toxicities (DLT)<br /><br>• Treatment-emergent adverse events<br /><br>• Treatment-related adverse events<br /><br>• Changes in vital signs, electrocardiogram (ECG), and clinical laboratory<br /><br>tests </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary study parameters/outcome of the study:<br /><br><br /><br>• PK parameters for AMG 199 following<br /><br>• intravenous (IV) administration including but not limited to maximum serum<br /><br>concentration (Cmax),minimum serum concentration (Cmin), area under the<br /><br>concentration-time curve (AUC) over the<br /><br>• dosing interval, accumulation following multiple<br /><br>• dosing, and, if feasible, half-life (t1/2)<br /><br>• Objective response (OR) per Response<br /><br>• Evaluation Criteria in Solid Tumors (RECIST) 1.and iRECIST<br /><br>• Duration of response (DOR)<br /><br>• Time to progression<br /><br>• Progression-free survival (PFS), 6-month and 1-year PFS<br /><br>• Overall survival (OS), 1 and 2-year OS</p><br>