Status:

COMPLETED

A Study of the Safety and Pharmacokinetics of AGS-22M6E in Subjects With Malignant Solid Tumors That Express Nectin-4

Lead Sponsor:

Astellas Pharma Inc

Collaborating Sponsors:

Agensys, Inc.

Seagen Inc.

Conditions:

Tumors

Medical Oncology

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

A study examining the safety of AGS-22M6E or ASG-22CE administered as monotherapy therapy in subjects with malignant solid tumors that express Nectin-4.

Detailed Description

AGS-22M6E and ASG-22CE are fully human monoclonal antibody conjugated to a cytotoxic agent monomethyl auristatin E (MMAE) targeting Nectin-4 (Agensys code name AGS-22). The main difference between AGS...

Eligibility Criteria

Inclusion

  • (For Dose Escalation and Dose Expansion)
  • Subjects must have a tumor positive for Nectin-4 expression (as measured by central laboratory using primary or metastatic tumor tissue
  • Histologically confirmed malignant solid tumors (excluding sarcoma) that have failed all FDA approved therapies indicated for the type of metastatic cancer and line of therapy or for which they were not a candidate to receive treatment
  • Measurable disease according to RECIST criteria (version 1.1) (Eisenhauer, et. al.) defined as tumor lesions that are accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of:
  • 10mm by CT scan (CT scan slice thickness no greater than 5mm
  • 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as nonmeasurable
  • 20 mm by chest X-ray
  • ≥ 15 mm in short axis for lymph nodes when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm)
  • Note: bone lesions, ascites, and pleural effusions are not considered measurable lesions
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Negative pregnancy test (women of childbearing potential)
  • Hematologic function, as follows:
  • a. Absolute neutrophil count (ANC) ≥ 1.0 x109 /L
  • b. Platelet count ≥ 100 x 109/L
  • c. Hemoglobin ≥ 8.5 g/dL
  • Renal function, as follows: serum creatinine ≤ 2.0 mg/dL, or measured 24 hour creatinine clearance of ≥ 45 mL/min
  • Total bilirubin ≤1.5 x upper limit of normal (ULN)
  • Serum albumin \> 2.5 g/dL
  • Aspartate aminotransferase (AST) ≤ 1.5 x ULN
  • Alanine aminotransferase (ALT) ≤ 1.5 x ULN
  • Gamma GT ≤1.5 ULN
  • International normalized ratio (INR) \< 1.5 (or ≤ 3 if on warfarin or other medications for therapeutic anticoagulation)
  • Women and men of childbearing potential must be advised and agree to practice effective methods of contraception during the course of the study
  • Inclusion Criteria for Dose Expansion Only:
  • In addition to the inclusion criteria listed above, the following criteria will also be required for each expansion cohort:
  • Expansion Cohort 1: Breast Cancer
  • Subjects with Histologically or cytologically diagnosed metastatic breast cancer
  • Expansion Cohort 2: Bladder Cancer
  • Histologically or cytologically confirmed bladder cancer with visceral metastases
  • Expansion Cohort 3: Lung plus other solid tumor cancer
  • Histologically or cytologically confirmed metastatic non-small cell lung cancer (NSCLC) or any other solid tumor cancer

Exclusion

  • Preexisting neuropathy Grade ≥ 3 or motor neuropathy Grade ≥ 2
  • Uncontrolled brain or epidural spinal metastases
  • Use of any investigational drug within 14 days or 5 half-lives prior to first dose of study drug
  • Any anticancer therapy including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer within 28 days prior to first dose of study drug
  • Active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of the first dose of study drug, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by medication
  • Known HIV or AIDS
  • Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
  • History of thromboembolic events and bleeding disorders ≤ 3 months (e.g.,deep vein thrombosis ( DVT) or pulmonary embolism ( PE)) prior to first dose of study drug
  • Major surgery within 28 days prior to first dose of study drug
  • Active infection requiring treatment ≤7 days prior to first dose of study drug
  • Anti-androgen therapy initiated within 28 days of enrollment (for prostate cancer patients only)
  • Positive Hepatitis B surface antigen test
  • Positive Hepatitis C antibody test

Key Trial Info

Start Date :

July 11 2011

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

April 27 2015

Estimated Enrollment :

34 Patients enrolled

Trial Details

Trial ID

NCT01409135

Start Date

July 11 2011

End Date

April 27 2015

Last Update

March 12 2024

Active Locations (9)

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Page 1 of 3 (9 locations)

1

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States, 94115

2

University of Colorado, Denver-Aurora

Aurora, Colorado, United States, 80045

3

Emory University

Atlanta, Georgia, United States, 30322

4

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115