A Study of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4

NCT02091999 | Completed Phase 1 FDA Drug

• 1 other identifier: ASG-22CE-13-2
• Study Type: interventional
• Target: 213
• Locations: 2 countries
• Sites: 21

Brief Summary

The purpose of this study is to evaluate the safety and pharmacokinetics of enfortumab vedotin as well as assess the immunogenicity and antitumor activity in subjects with metastatic urothelial cancer and other malignant solid tumors that express Nectin-4.

Conditions

Metastatic Urothelial Cancer and Other Malignant Solid Tumors

Keywords

enfortumab vedotin; Metastatic Urothelial Cancer; Safety; AGS-22C3E; EV-101; Nectin 4 protein, humans; Clinical Trial, Phase 1; ASG-22CE; ASG-22ME; Pharmacokinetics of ASG-22CE

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 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 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 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 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 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 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 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 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 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 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 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 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 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 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 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months

Secondary Outcomes (7)

• Incidence of Anti-Drug Antibody (ADA)

  up to 24 months

• Tumor response

  up to 24 months

• Objective response rate

  up to 24 months

• Disease control rate

  up to 24 months

• Progression Free Survival (PFS)

  36 months

Study Arms (5)

Part A enfortumab vedotin Dose Escalation (Dose Levels 1-4)

EXPERIMENTAL

All subjects will receive a single 30 minute intravenous (IV) infusion of enfortumab vedotin once weekly for the first 3 weeks of every 4 week cycle (i.e., on Days 1, 8 and 15).

Drug: enfortumab vedotin

Part B enfortumab vedotin Renal Insufficiency Expansion

EXPERIMENTAL

Subjects will receive a single 30 minute IV infusion of enfortumab vedotin at a dose level below and escalated up to the preliminary RP2D once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8 and 15) until disease progression, intolerability of the investigational product or consent withdrawal. A cycle is 4 weeks.

Drug: enfortumab vedotin

Part B enfortumab vedotin NSCLC Expansion

EXPERIMENTAL

Subjects will receive a single 30 minute IV infusion of enfortumab vedotin at the preliminary RP2D once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8 and 15) until disease progression, intolerability of the investigational product or consent withdrawal. A cycle is 4 weeks.

Drug: enfortumab vedotin

Part B enfortumab vedotin Ovarian Cancer Expansion

EXPERIMENTAL

Subjects will receive a single 30 minute IV infusion of enfortumab vedotin at the preliminary RP2D once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8 and 15) until disease progression, intolerability of the investigational product or consent withdrawal. A cycle is 4 weeks.

Drug: enfortumab vedotin

Part C enfortumab vedotin CPI Treated Expansion

EXPERIMENTAL

Subjects will receive a single 30 minute IV infusion of enfortumab vedotin at the preliminary RP2D once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8 and 15). A cycle is 4 weeks. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin, Investigator decision or consent withdrawal.

Drug: enfortumab vedotin

Interventions

enfortumab vedotin DRUG

intravenous (IV) infusion

Also known as: ASP7465, ASG-22CE, ASG-22ME

Part A enfortumab vedotin Dose Escalation (Dose Levels 1-4); Part B enfortumab vedotin NSCLC Expansion; Part B enfortumab vedotin Ovarian Cancer Expansion; Part B enfortumab vedotin Renal Insufficiency Expansion; Part C enfortumab vedotin CPI Treated Expansion

Eligibility Criteria

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

You may qualify if:

• Dose Escalation, Renal insufficiency and CPI-Treated Expansion cohorts: 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.
• Ovarian Expansion Cohort: Subjects with recurrent disease or histologically or cytologically confirmed Stage III/IV diagnosis of epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma who have previously progressed while receiving or within 6 months of completing a platinum-containing regimen.
• NSCLC Expansion Cohort: Histologic or cytologic diagnosis of NSCLC (squamous or non-squamous or NSCLC-not specified)
• Dose Escalation, Renal insufficiency, NSCLC and CPI-Treated Expansion Cohorts: For subjects with urothelial cancer and NSCLC: Subjects must submit a tumor tissue for Nectin-4 expression. Enrollment for these subjects is not dependent on the immunohistochemistry using the H-Score (IHC H-Score).
• Ovarian Expansion Cohort: Subjects must have tumor tissue positive (IHC H-score ≥150) for Nectin-4 expression
• For Dose Escalation, NSCLC and Ovarian Expansion Cohorts: Subject must have failed at least one prior chemotherapy regimen for metastatic disease (urothelial and bladder cancer subjects are not required to have failed prior chemotherapy regimen if considered unfit for cisplatin-based chemotherapy)
• For the CPI-Treated Expansion Cohort: Subject must have received prior treatment with a CPI in the metastatic setting.
• Subjects must have measurable disease according to RECIST (version 1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of ≥ 3 months
• Negative pregnancy test (women of childbearing potential)
• Hematologic function, as follows (no red blood cell or platelet transfusions are allowed within 14 days of the first dose of enfortumab vedotin):
• Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L
• Platelet count ≥ 100 x 10\^9/L
• Hemoglobin ≥ 9 g/dL

You may not qualify if:

• Preexisting sensory neuropathy Grade ≥ 2
• Preexisting 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 within 14 days prior to the first dose of study drug, 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-glycoprotein (P-gp) inducers/inhibitors or strong cytochrome P4503A (CYP3A) inhibitors within 14 days prior to the first dose of study drug
• 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
• Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of enfortumab vedotin.
• Known Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS)
• Subjects with a positive Hepatitis B surface antigen and/or antihepatitis B core antibody. Subjects with a negative polymerase chain reaction (PCR) assay are permitted with appropriate antiviral prophylaxis.
• Active Hepatitis C infection. Subjects who have been treated for Hepatitis C infection can be included if they have documented sustained virologic response of ≥ 12 weeks.
• 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 enfortumab vedotin (ASG-22CE)
• Major surgery within 28 days prior to first dose of study drug

Sponsors & Collaborators

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

Study Sites (21)

Site US00012

Los Angeles, California, 90033, United States

Location

Site US00019

Stanford, California, 94305, United States

Location

Site US00017

Aurora, Colorado, 80045, United States

Location

Site US00006

New Haven, Connecticut, 06520, United States

Location

Site US00007

Miami, Florida, 33136, United States

Location

Site US00008

Tampa, Florida, 33612, United States

Location

Site US00004

Fairway, Kansas, 66205, United States

Location

Site US00005

Ann Arbor, Michigan, 48109, United States

Location

Site US00003

Detroit, Michigan, 48201, United States

Location

Site US00021

Las Vegas, Nevada, 89119, United States

Location

Site US00018

New York, New York, 10029, United States

Location

Site US00002

New York, New York, 10065, United States

Location

Site US00023

Chapel Hill, North Carolina, 27599, United States

Location

Site US00013

Philadelphia, Pennsylvania, 19111, United States

Location

Site US00020

Pittsburgh, Pennsylvania, 15232, United States

Location

Site US00024

Fairfax, Virginia, 22031, United States

Location

Site US00009

Madison, Wisconsin, 53792, United States

Location

Site US00015

Milwaukee, Wisconsin, 53226, United States

Location

Site CA00011

Calgary, Alberta, T2N 4N2, Canada

Location

Site CA00001

Edmonton, Alberta, T6G 1Z2, Canada

Location

Site CA00010

Toronto, Ontario, M5G 2M9, Canada

Location

Related Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

MeSH Terms

Interventions

enfortumab vedotin

Study Officials

• Medical Director

  Agensys, 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
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 18, 2014
• First Posted: March 19, 2014
• Study Start: May 14, 2014
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022
• 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

US (18); CA (3)