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

JRCT ID: jRCT2080225224

Registered date:10/06/2020

Basic Information

• Recruitment status: terminated
• Health condition(s) or Problem(s) studied: MUC17-positive Solid Tumors
• Date of first enrollment: 20/01/2020
• Target sample size: 240
• Countries of recruitment: United States,Austria,,France,Germany,Korea,Netherland,Spain,Taiwan
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc : AMG 199
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : AMG 199 0.0025~10 mg will be administered intravenously over a short period of time (approximately 60 minutes). AMG 199 will be administered on Days 1, 3, 8, 15, and 22 of a 28-day cycle for Cycle 1 and once weekly (Days 1, 8, 15, and 22) for Cycles 2 through 6 of a 28-day cycle. Cycles 2 and 4 are followed by a 2-week rest period.

Outcome(s)

Primary Outcome

safety
1. Incidence of Dose-limiting toxicities (DLT) [ Time Frame: 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).
2. Incidence of Treatment-emergent adverse events (TEAEs) [ Time Frame: 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).
3. Incidence of Treatment-related adverse events (TRAEs) [ Time Frame: 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).
4. Number of subjects with changes in vital signs [ Time Frame: 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).
5. Number of subjects with changes in clinical laboratory tests [ Time Frame: 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).
6. Number of subjects with changes in electrocardiogram (ECG) [ Time Frame: 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 Outcome

efficacy
pharmacokinetics
1. Maximum serum concentration (Cmax) of AMG 199 [ Time Frame: 3 years ]
To characterize the PK (Pharmacokinetics) of AMG 199.
2. Minimum serum concentration (Cmin) of AMG 199 [ Time Frame: 3 years ]
To characterize the PK (Pharmacokinetics) of AMG 199.
3. Area under the concentration-time curve (AUC) of AMG 199 [ Time Frame: 3 years ]
To characterize the PK (Pharmacokinetics) of AMG 199.
4. Accumulation following multiple dosing of AMG 199 [ Time Frame: 3 years ]
To characterize the PK (Pharmacokinetics) of AMG 199.
5. Half-life (t1/2) of AMG 199 [ Time Frame: 3 years ]
To characterize the PK (Pharmacokinetics) of AMG 199.
6. Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST. [ Time Frame: 32 years ]
To evaluate preliminary anti-tumor activity of AMG 199
7. Duration of response (DOR). [ Time Frame: 3 years ]
To evaluate preliminary anti-tumor activity of AMG 199
8. Time to progression (TTP) [ Time Frame: 3 years ]
To evaluate preliminary anti-tumor activity of AMG 199
9. Progression-free survival (PFS), 6-month PFS [ Time Frame: 6 months ]
To evaluate preliminary anti-tumor activity of AMG 199
10. Progression-free survival (PFS), 1-year PFS [ Time Frame: 1 year ]
To evaluate preliminary anti-tumor activity of AMG 199
11. Overall survival (OS), 1-year OS. [ Time Frame: 1 year ]
To evaluate preliminary anti-tumor activity of AMG 199
12. Overall survival (OS), 2-year OS [ Time Frame: 2 years ]
To evaluate preliminary anti-tumor activity of AMG 199

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 99age old
• Gender: Both

Include criteria

1. 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.
2. 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.
3. 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.
4. 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.

Exclude criteria

1. Any anticancer therapy or immunotherapy within 4 weeks of start of first dose.
2. Central nervous system (CNS) metastases, leptomeningeal, or spinal cord compression.
3. 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.

Related Information

• Primary Sponsor: Amgen K.K.
• Secondary ID(s): NCT04117958,JapicCTI-205320