A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer

Astellas Pharma Global Development, Inc.11 个研究点分布在 2 个国家目标入组 93 人开始时间: 2013年11月14日最近更新: 2024年11月1日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Astellas Pharma Global Development, Inc.
入组人数: 93
试验地点: 11
主要终点: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The objectives of this study are to assess the safety, pharmacokinetics, immunogenicity and anti-tumor activity of AGS15E in subjects with metastatic urothelial cancer who failed at least one prior chemotherapy regimen for metastatic disease.

详细描述

All subjects will receive a single intravenous infusion of AGS15E once weekly for 3 weeks of every 4 weeks. A cycle is 4 weeks. Subjects will continue treatment until disease progression, intolerability of AGS15E, investigator decision, or consent withdrawal.

In subjects who discontinue therapy without documented disease progression and who still consent to study procedures, every effort should be made to continue monitoring their disease status by radiographic imaging until progression is documented, or new anticancer therapy, or death. All subjects will continue to be followed for survival until withdrawal of consent or study closure.

If assessed as complete response (CR) or partial response (PR) per local review a confirmatory scan will be performed no less than 4 weeks from previous scan and preferably at week 5. Tumor imaging should also be performed whenever disease progression is suspected.

Images will be sent to a central third party imaging vendor for an independent assessment per RECIST version 1.1. Although the imaging studies will be reviewed by a central third party imaging vendor in a retrospective fashion, all clinical decisions will be based on the interpretation of the investigator at the site treating the subject.

Post-Treatment Follow-up Progression Free Survival:

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
•Part A: Subject must have failed at least one prior chemotherapy regimen for metastatic disease and/or is unfit for cisplatin-based chemotherapy.
•Part B: Subject must not have received any prior lines of chemotherapy in the metastatic setting (prior treatment with immunotherapy is allowed).
•Part C (CPI-Treated Expansion): Subject must have received prior treatment with a CPI in the metastatic setting
•Subjects must have measureable disease according to RECIST (version 1.1).
•Part A and C: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
•Part B: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
•Life expectancy of ≥ 3 months
•Adequate hematologic function
•Parts A and C: Renal function, as follows: serum creatinine ≤ 2.0 mg/dL, or measured 24 hour creatinine clearance of ≥ 45 mL/min
•Part B: Renal function, as follows: creatinine clearance estimate ≥ 15 mL/min and <60 mL/min by Cockcroft Gault equation adjusted for body weight
•Adequate liver function

排除标准

•Preexisting sensory neuropathy Grade ≥ 2 or motor neuropathy Grade ≥ 2
•Uncontrolled central nervous system metastases
•Use of any investigational drug within 14 days prior to the first dose of study drug
•Any anticancer therapy, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer (anti-hormonal therapy given as adjuvant therapy for early-stage estrogen receptor (ER) positive breast cancer is not considered cancer therapy for the purpose of this protocol)
•Subjects with Immunotherapy related adverse events requiring high doses of steroids (≥ 40 mg/day of prednisone) are not eligible
•Any P-gp inducers/inhibitors or strong CYP3A inhibitors within 14 days prior to the first dose of study drug
•History of thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) prior to the first dose of study drug
•Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication
•Known HIV or AIDS
•Positive Hepatitis B surface antigen test
•Positive Hepatitis C antibody test
•Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
•Known sensitivity to any of the ingredients of the investigational product AGS15E
•Major surgery within 28 days prior to first dose of study drug
•History of a primary invasive malignancy not listed in the inclusion criteria, which has not been in remission for at least 3 years. The following are exempt from the 3 year limit:
•Non-melanoma skin cancer;
•adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is undetectable;
•cervical carcinoma in situ on biopsy or squamous intraepithelial lesion on Pap smear; and
•definitively treated, stage I/II ER+ breast cancer
•Active infection requiring treatment ≤ 7 days before first dose of study drug
•History of uncontrolled diabetes mellitus or diabetic neuropathy
•Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study
•Has ocular conditions such as:
•Active infection or corneal ulcer (e.g., keratitis)
•Monocularity
•History of corneal transplantation
•Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
•Uncontrolled glaucoma (topical medications allowed)
•Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder

研究组 & 干预措施

Part A: AGS-15E Dose Escalation (Dose Levels 1-6)

Experimental

Subjects will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Additional subjects may be enrolled for expansion of these dose levels to further evaluate the safety and efficacy, as recommended by a data review team (DRT).

干预措施: AGS15E (Drug)

Part B: AGS-15E Cisplatin Therapy -ineligible Expansion

Experimental

Urothelial subjects who have not received any prior lines of therapy an who are unfit for Cisplatin therapy (Cis-ineligible) will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Subjects will initially be dosed one dose level below the preliminary recommended phase 2 dose (RP2D).

干预措施: AGS15E (Drug)

Part C: AGS15E Immune Checkpoint Inhibitor Treated Expansion

Experimental

Subjects previously treated with immune checkpoint inhibitors (CPI) in the metastatic setting will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Subjects will be dosed at the RP2D.

干预措施: AGS15E (Drug)

Part A: AGS15E Dose Expansion

Experimental

Subjects will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks.

干预措施: AGS15E (Drug)

结局指标

主要结局

Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI)