ASG-15ME is a Study of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer

NCT ID: NCT01963052

Last Updated: 2024-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-14
• Study Completion Date: 2019-07-08

Brief Summary

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.

Detailed Description

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:

Subjects who discontinued study treatment for reasons other than radiographic disease progression will continue for a maximum of up to 12 months following the last dose of study drug until radiologically confirmed progression, initiation of a new anticancer therapy, death, loss to follow-up or withdraw consent for further follow-up, whichever of these events occurs first. The purpose of the post-treatment follow-up is to ascertain the duration of progression-free survival for all subjects enrolled in the study.

Conditions

Metastatic Urothelial Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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).

Group Type: EXPERIMENTAL

AGS15E

Intervention Type: DRUG

intravenous (IV) infusion

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

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).

Group Type: EXPERIMENTAL

AGS15E

Intervention Type: DRUG

intravenous (IV) infusion

Part C: AGS15E Immune Checkpoint Inhibitor Treated Expansion

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.

Group Type: EXPERIMENTAL

AGS15E

Intervention Type: DRUG

intravenous (IV) infusion

Part A: AGS15E Dose Expansion

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.

Group Type: EXPERIMENTAL

AGS15E

Intervention Type: DRUG

intravenous (IV) infusion

Interventions

AGS15E

intravenous (IV) infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seagen Inc.

INDUSTRY

Sponsor Role: collaborator

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Associate Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development, Inc.

Locations

Site US00006

Birmingham, Alabama, United States

Site US00002

New Haven, Connecticut, United States

Site US00001

Detroit, Michigan, United States

Site US00003

St Louis, Missouri, United States

Site US00009

Buffalo, New York, United States

Site US00011

Pittsburgh, Pennsylvania, United States

Site US00010

Nashville, Tennessee, United States

Site US00008

Seattle, Washington, United States

Site CA00004

Vancouver, British Columbia, Canada

Site CA00007

Hamilton, Ontario, Canada

Site CA00005

Toronto, Ontario, Canada

Countries

United States; Canada

References

Petrylak DP, Eigl BJ, George S, Heath EI, Hotte SJ, Chism DD, Nabell LM, Picus J, Cheng SY, Appleman LJ, Sonpavde GP, Morgans AK, Pourhosseini P, Wu R, Standley L, Croitoru R, Yu EY. Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma. Clin Cancer Res. 2024 Jan 5;30(1):63-73. doi: 10.1158/1078-0432.CCR-22-3627.

Reference Type: DERIVED

PMID: 37861407 (View on PubMed)

Other Identifiers

AGS15E-13-1

Identifier Type: -

Identifier Source: org_study_id