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

NCT01963052 | Completed Phase 1 FDA Drug

• 1 other identifier: AGS15E-13-1
• Study Type: interventional
• Target: 93
• Locations: 2 countries
• Sites: 11

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.

Conditions

Metastatic Urothelial Cancer

Keywords

Metastatic Urothelial Cancer; AGS15E; AGS15E-13-1; ASG-15ME; Pharmacokinetics of AGS15E

Outcome Measures

Primary Outcomes (9)

• Incidence of adverse events

  up to 36 months

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

  Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax)

  Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Trough concentration (Ctrough)

  Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax)

  Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7)

  Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2)

  Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL)

  Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss)

  Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

Secondary Outcomes (6)

• Incidence of Anti-Drug Antibody (ADA)

  Up to 26 months

• Tumor response

  Up to 26 months

• Objective response rate

  Up to 26 months

• Disease control rate

  Up to 26 months

• Progression free survival

  Up to 36 months

Study Arms (4)

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).

Drug: AGS15E

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).

Drug: AGS15E

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.

Drug: AGS15E

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.

Drug: AGS15E

Interventions

AGS15E DRUG

intravenous (IV) infusion

Part A: AGS-15E Dose Escalation (Dose Levels 1-6); Part A: AGS15E Dose Expansion; Part B: AGS-15E Cisplatin Therapy -ineligible Expansion; Part C: AGS15E Immune Checkpoint Inhibitor Treated Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Non-melanoma skin cancer;

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Seagen Inc.: collaborator

Study Sites (11)

Site US00006

Birmingham, Alabama, 35294, United States

Location

Site US00002

New Haven, Connecticut, 06510, United States

Location

Site US00001

Detroit, Michigan, 48201, United States

Location

Site US00003

St Louis, Missouri, 63110, United States

Location

Site US00009

Buffalo, New York, 14263, United States

Location

Site US00011

Pittsburgh, Pennsylvania, 15232, United States

Location

Site US00010

Nashville, Tennessee, 37212, United States

Location

Site US00008

Seattle, Washington, 98109, United States

Location

Site CA00004

Vancouver, British Columbia, V5Z 1H5, Canada

Location

Site CA00007

Hamilton, Ontario, L8V 5C2, Canada

Location

Site CA00005

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (1)

• 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.

  PMID: 37861407 DERIVED

MeSH Terms

Interventions

sirtratumab vedotin

Study Officials

• Associate Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2013
• First Posted: October 16, 2013
• Study Start: November 14, 2013
• Primary Completion: July 8, 2019
• Study Completion: July 8, 2019
• Last Updated: November 1, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

CA (3); US (8)