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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01409135
Recruitment Status : Completed
First Posted : August 4, 2011
Last Update Posted : October 7, 2015
Agensys, Inc.
Seagen Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc

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.

Condition or disease Intervention/treatment Phase
Tumors Medical Oncology Neoplasms Drug: AGS-22M6E Drug: ASG-22CE Phase 1

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-22M6E and ASG-22CE is the change in cell line for antibody production. AGS-22M6E and ASG-22CE will be administered at mg/kg doses based on the subjects weight at baseline and doses will not change unless the subjects weight changes by ≥ 10% from their baseline weight or the investigational product Dosage Assessment criteria is met.

Subjects will be prescreened for Nectin-4 expression prior to undergoing screening procedures for the main study. Subjects with tumors positive for Nectin-4 expression may be screened for eligibility into the main study. The dose escalation period is estimated to take between 12 and 18 months depending on whether 3 or 6 subjects are enrolled in a given dose cohort, and the availability of consenting subjects.

Subjects will be treated in the dose escalation phase of the study until the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) has been determined by the data review team (DRT). After the RDE has been determined, subjects will be enrolled into 1 of 3 expansion cohorts. There will be 3 expansion cohorts, each targeting a specific cancer (i.e.,Breast, Bladder and Lung plus other solid tumor cancers). The DRT may recommend stopping the study, adjusting the dose or amending the trial at any time.

The clinical bridging to the ASG-22CE involves treating the subjects with ASG-22CE, irrespective of cancer type, at the next lowest dose level previously determined to be safe for AGS-22M6E. After the initial subjects are treated at the bridging dose with ASG-22CE and have completed the safety assessment, future subjects will only be treated with ASG-22CE throughout the remainder of the study.

A disease assessment will be performed by the investigator at Week 8 (± 14 days). Subjects without evidence of disease progression may continue to receive treatment until disease progression or intolerability.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS-22M6E or ASG-22CE Given as Monotherapy Followed by Expansion Cohorts in Subjects With Malignant Solid Tumors That Express Nectin-4
Study Start Date : June 2011
Actual Primary Completion Date : April 2015
Actual Study Completion Date : April 2015

Arm Intervention/treatment
Experimental: AGS-22M6E-11-1 Dose Level 1 Drug: AGS-22M6E
IV Infusion

Experimental: AGS-22M6E-11-1 Dose Level 2 Drug: AGS-22M6E
IV Infusion

Experimental: AGS-22M6E-11-1 Dose Level 3 Drug: AGS-22M6E
IV Infusion

Experimental: AGS-22M6E-11-1 Dose Level 4 Drug: AGS-22M6E
IV Infusion

Experimental: AGS-22M6E-11-1 Dose Level 5 Drug: AGS-22M6E
IV Infusion

Experimental: AGS-22M6E-11-1 Dose Level 6 Drug: AGS-22M6E
IV Infusion

Experimental: ASG-22CE Expansion Cohort 1
Breast Cancer
Drug: ASG-22CE
IV Infusion

Experimental: ASG-22CE Expansion Cohort 2
Bladder Cancer
Drug: ASG-22CE
IV Infusion

Experimental: ASG-22CE Expansion Cohort 3
Lung plus other solid tumor cancers
Drug: ASG-22CE
IV Infusion

Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 28 days after the last dose of study drug ]
  2. Composite of Pharmacokinetics: Ceoi or Cmax, Ctrough, Tmax, AUC0-21, t½, CL, Vss [ Time Frame: Up to 28 days after the last dose of study drug ]
    Concentration at the end of infusion (Ceoi) or Cmax, trough concentration (Ctrough), Tmax, partial AUC after first dose (AUC0-21), terminal or apparent terminal half-life (t1/2), systemic clearance (CL), volume of distribution at steady state (Vss)

Secondary Outcome Measures :
  1. Incidence of anti-drug antibody formation [ Time Frame: Up to 28 days after the last dose of study drug ]
  2. Objective tumor response rate [ Time Frame: Every 8 weeks (± 14 days) ]
    Incidence of a tumor response is defined as a complete or partial response per Response Criteria for Solid Tumors (RECIST version 1.1)

  3. Disease Control Rate [ Time Frame: Every 8 weeks (± 14 days) ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria: (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 Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01409135

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United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Colorado
University of Colorado, Denver-Aurora
Aurora, Colorado, United States, 80045
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Karmanos Cancer institute
Detroit, Michigan, United States, 48201
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, North Carolina
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Sponsors and Collaborators
Astellas Pharma Inc
Agensys, Inc.
Seagen Inc.
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Study Director: Medical Monitor Agensys, Inc.
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Responsible Party: Astellas Pharma Inc Identifier: NCT01409135    
Other Study ID Numbers: AGS-22M6E-11-1
First Posted: August 4, 2011    Key Record Dates
Last Update Posted: October 7, 2015
Last Verified: October 2015
Keywords provided by Astellas Pharma Inc:
Nectin 4 protein, humans
Pharmacokinetics of AGS-22M6E
Pharmacokinetics of ASG-22CE
Clinical Trial, Phase 1
Additional relevant MeSH terms:
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