Primary• To evaluate the safety and tolerability of AMG 199 in adult subjects• To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) Secondary• To characterize the PK of AMG 199 • To evaluate preliminary anti-tumor…
ID
Source
Brief title
Condition
- Other condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Health condition
maagkanker, kanker van de maag-slokdarmovergang, darm- en pancreaskanker
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary study parameters/outcome of the study:
• Dose-limiting toxicities (DLT)
• Treatment-emergent adverse events
• Treatment-related adverse events
• Changes in vital signs, electrocardiogram (ECG), and clinical laboratory
tests
Secondary outcome
Secondary study parameters/outcome of the study:
• PK parameters for AMG 199 following
• intravenous (IV) administration including but not limited to maximum serum
concentration (Cmax),minimum serum concentration (Cmin), area under the
concentration-time curve (AUC) over the
• dosing interval, accumulation following multiple
• dosing, and, if feasible, half-life (t1/2)
• Objective response (OR) per Response
• Evaluation Criteria in Solid Tumors (RECIST) 1.and iRECIST
• Duration of response (DOR)
• Time to progression
• Progression-free survival (PFS), 6-month and 1-year PFS
• Overall survival (OS), 1 and 2-year OS
Background summary
Bispecific T cell engager (BiTEs) are designed to direct T cells towards target
cells. The proximity induced by the BiTE triggers target cell specific
cytotoxicity which closely resembles standard cytotoxic T lymphocyte
activation. Blinatumomab (BLINCYTO* ), a CD19 BiTE*, is approved for the
treatment of acute lymphoblastic leukemia (ALL). AMG 199 is an HLE BiTE *
antibody construct designed to direct T cells towards MUC17-expressing cells.
In AMG 199 the binding arms for MUC17 and CD3 are genetically fused to the
N-terminus of a single chain IgG Fc (fragment crystallizable; scFc) region.
The fusion to a Fc domain is a well-established strategy to prolong the
half-life of protein therapeutics, such as cytokines, growth factors, and
bispecific antibodies, with several approved for the treatment of cancer
(Kontermann, 2011). The extended half-life of Fc fusion proteins is due to
their interaction with the neonatal Fc receptor, which results in a protected
intracellular protein reservoir that is recycled to the extracellular space
(Rath, et al., 2015).
A detailed description of the chemistry and pharmacology of AMG 199 is provided
in the AMG 199 Investigator*s Brochure.
Study objective
Primary
• To evaluate the safety and tolerability of AMG 199 in adult subjects
• To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose
(RP2D)
Secondary
• To characterize the PK of AMG 199
• To evaluate preliminary anti-tumor activity of AMG 199
Study design
This is an open-label, ascending, multiple dose, phase 1 study evaluating AMG
199 in subjects with MUC17-positive solid tumors. The study will consist of:
• Dose-exploration phase
• Dose-expansion phase
The dose-exploration phase of the study will estimate the MTD of AMG 199 using
a Bayesian logistic regression model (BLRM). A RP2D may be identified based on
emerging safety, efficacy, and PD data prior to reaching an MTD. Alternative
dosing schedule(s) may be explored based on emerging PK and safety data.
Following the dose-exploration phase, a 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.
Intervention
AMG 199 will be administered as a short intravenous infusion given over
approximately 60 minutes through a catheter (plastic needle) in a vein (for
example, in your arm), or can be administered as extended intravenous infusion
(continuous infusion).
Study burden and risks
Key Risks for AMG 199:
Cytokine Release Syndrome (CRS)/ Infusion-Related Reactions
Gastrointestinal Toxicity
Neurologic Events
Tumor Lysis Syndrome (TLS
Sucrose Toxicity
Embryofetal and Reproductive System
Minervum 7061
Breda 4817 ZK
NL
Minervum 7061
Breda 4817 ZK
NL
Listed location countries
Age
Inclusion criteria
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.
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.
Refer to 5.2 of the protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | NCT04117958 |
| EudraCT | EUCTR2019-002708-42-NL |
| CCMO | NL71930.056.19 |