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Trial record 1 of 1 for:    NCT02091999
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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

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ClinicalTrials.gov Identifier: NCT02091999
Recruitment Status : Recruiting
First Posted : March 19, 2014
Last Update Posted : October 18, 2018
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information
First Submitted Date  ICMJE March 18, 2014
First Posted Date  ICMJE March 19, 2014
Last Update Posted Date October 18, 2018
Actual Study Start Date  ICMJE June 4, 2014
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2016)
  • Incidence of adverse events [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 18, 2014)
  • Incidence of adverse events [ Time Frame: up to 24 months ]
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 ]
Change History Complete list of historical versions of study NCT02091999 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2016)
  • Incidence of Anti-Drug Antibody (ADA) [ Time Frame: up to 24 months ]
  • Tumor response [ Time Frame: up to 24 months ]
    Incidence of tumor response defined as either a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) that is confirmed ≥ 28 days later
  • Objective response rate [ Time Frame: up to 24 months ]
    Defined as the percentage of subjects who experience a best response of either CR or PR in that cohort. CR and PR must be confirmed ≥ 28 days later.
  • Disease control rate [ Time Frame: up to 24 months ]
    Defined as the percentage of subjects who experience a best response of CR, PR or stable disease (SD)
  • Progression Free Survival (PFS) [ Time Frame: 36 months ]
    Time from the date of first infusion to the earliest date of documented disease progression per radiological evidence or death from any cause
  • Overall Survival [ Time Frame: 36 months ]
    Time from the date of first infusion until the date of death from any cause.
  • Duration of Response [ Time Frame: 36 months ]
    Time from the date of the first response complete response (CRC) or partial response (PR) to the earliest date of disease progression or death from any cause. DOR is only defined for subjects who have best overall response of CR or PR
Original Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2014)
  • Incidence of Anti-Drug Antibody (ADA) [ Time Frame: up to 24 months ]
  • Tumor response [ Time Frame: up to 24 months ]
    Incidence of tumor response defined as either a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) that is confirmed ≥ 28 days later
  • Objective response rate [ Time Frame: up to 24 months ]
    Defined as the percentage of subjects who experience a best response of either CR or PR in that cohort. CR and PR must be confirmed ≥ 28 days later.
  • Disease control rate [ Time Frame: up to 24 months ]
    Defined as the percentage of subjects who experience a best response of CR, PR or stable disease (SD)
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4
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.
Detailed Description

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

This is a 3 part study. Part A will evaluate enfortumab vedotin in subjects with histologically confirmed malignant solid tumors (excluding sarcomas) that are resistant or have recurred. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin, investigator decision or consent withdrawal. Part A will follow a modified Continual Reassessment Method (mCRM).

Part B, will evaluate enfortumab vedotin in 3 different expansion cohorts: 1) Urothelial cancer subjects with renal insufficiency defined as a Creatinine Clearance ≥ 15 ml/min and < 30 ml/min, 2) subjects with Metastatic Non Small Cell Lung Cancer (NSCLC) and 3) subjects with Metastatic Ovarian Cancer. With the exception of the renal insufficiency cohort, enrollment into Part B will occur at the recommended phase 2 dose (RP2D) established in Part A. Enrollment into the renal insufficiency cohort will begin at starting dose and escalated using a 3 + 3 dose escalation design. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin or consent withdrawal.

Part C will evaluate enfortumab vedotin at the RP2D (determined from Part A) in subjects who have been previously treated with immune checkpoint inhibitors (CPI) in the metastatic setting. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin, investigator decision or consent withdrawal.

All subjects will be followed post-treatment every 2 months via disease assessment or telephone contact to obtain information on disease progression and death.

Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Urothelial Cancer and Other Malignant Solid Tumors
Intervention  ICMJE Drug: enfortumab vedotin
intravenous (IV) infusion
Other Names:
  • ASP7465
  • ASG-22CE
  • ASG-22ME
Study Arms
  • Experimental: Part A enfortumab vedotin Dose Escalation (Dose Levels 1-4)
    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).
    Intervention: Drug: enfortumab vedotin
  • Experimental: Part B enfortumab vedotin Renal Insufficiency Expansion
    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.
    Intervention: Drug: enfortumab vedotin
  • Experimental: Part B enfortumab vedotin NSCLC Expansion
    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.
    Intervention: Drug: enfortumab vedotin
  • Experimental: Part B enfortumab vedotin Ovarian Cancer Expansion
    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.
    Intervention: Drug: enfortumab vedotin
  • Experimental: Part C enfortumab vedotin CPI Treated Expansion
    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.
    Intervention: Drug: enfortumab vedotin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 9, 2018)
215
Original Estimated Enrollment  ICMJE
 (submitted: March 18, 2014)
45
Estimated Study Completion Date December 2020
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • Renal function, as follows: Dose Escalation, NSCLC, Ovarian, and CPI Treated Expansion Cohorts: creatinine clearance of ≥ 30 mL/min by the Cockcroft-Gault equation or as measured by 24 hour urine collection. For the Renal Insufficiency Expansion Cohort: creatinine clearance estimate ≥15 ml/min and <30 ml/min by Cockcroft-Gault equation or as measured by 24 hour urine collection.
  • Total bilirubin ≤ 1.5 x ULN (upper limit of normal)
  • Serum albumin ≥2.5 g/dL
  • Aspartate aminotransferase (AST) ≤ 1.5 x ULN
  • Alanine aminotransferase (ALT) ≤ 1.5 x ULN
  • International normal ratio (INR) < 1.3 or ≤ institutional ULN (or ≤ 3.0 if on therapeutic anticoagulation)
  • Sexually active fertile subjects, and their partners, must agree to use medically accepted double-barrier methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the study and at least 6 months after termination of study therapy
  • Competent to comprehend, sign, and date an independent ethics committee/institutional review board/research ethics board (IEC/IRB/REB) approved informed consent form

Exclusion Criteria:

  • 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
  • History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Subjects with nonmelanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low risk localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any time (if complete resection was performed) are allowed.
  • History of uncontrolled diabetes mellitus or diabetic neuropathy within 3 months of the first dose of study drug. Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) ≥ 8% or HbA1c > 7 to < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
  • Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of first dose of enfortumab vedotin. Routine antimicrobial prophylaxis is permitted.
  • 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
  • Any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures
  • 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Astellas Pharma Global Development 800-888-7704 Astellas.registration@astellas.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02091999
Other Study ID Numbers  ICMJE ASG-22CE-13-2
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Study Sponsor  ICMJE Astellas Pharma Global Development, Inc.
Collaborators  ICMJE Seattle Genetics, Inc.
Investigators  ICMJE
Study Director: Medical Director Agensys, Inc.
PRS Account Astellas Pharma Inc
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP