Clinical Trials /

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

Description:

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.

Related Conditions:
  • Bladder Carcinoma
  • Fallopian Tube Carcinoma
  • Malignant Ovarian Epithelial Tumor
  • Malignant Solid Tumor
  • Primary Peritoneal Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: ASG-22CE-13-2
  • NCT ID: NCT02091999

Conditions

  • Metastatic Urothelial Cancer and Other Malignant Solid Tumors

Interventions

DrugSynonymsArms
ASG-22CEPart B ASG-22CE Ovarian Cancer Expansion

Purpose

The purpose of this study is to evaluate the safety and pharmacokinetics ASG-22CE as well as assess the immunogenicity and antitumor activity in subjects with metastatic urothelial cancer and other malignant solid tumors.

Detailed Description

All subjects will receive a single 30 minute IV infusion of ASG-22CE once weekly for 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 ASG-22CE 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 ASG-22CE, investigator decision or consent withdrawal. Part A will follow a modified Continual Reassessment Method (mCRM).

Part B, will evaluate ASG-22CE in 3 different expansion cohorts: 1) Urothelial cancer subjects who have not received any prior lines of therapy and who are unfit for Cisplatin-based chemotherapy (Cisineligible) defined as a Creatinine Clearance ≥ 15 ml/min and < 60 ml/min, 2) subjects with Metastatic Non Small Cell Lung Cancer (NSCLC) and 3) subjects with Metastatic Ovarian Cancer. Enrollment into Part B will occur after the maximum tolerated dose (MTD) has been assessed in Part A, and the preliminary recommended phase 2 dose (RP2D) has been established. Subjects will continue treatment until disease progression, intolerability of ASG-22CE or consent withdrawal.

Part C will evaluate ASG-22CE at the preliminary 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 ASG-22CE, 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.

For Part A (Dose Escalation) and Part B (Cis-ineligible), a data review team (DRT) will review cumulative unaudited data on an interim basis to explore additional doses and/or schedules, or the expansion of existing cohorts. Doses intermediate to those predefined in the protocol may be explored with DRT endorsement.

Trial Arms

NameTypeDescriptionInterventions
Part A ASG-22CE Dose Escalation (Dose Levels 1-4)ExperimentalAll subjects will receive a single 30 minute intravenous (IV) infusion of ASG-22CE once weekly for the first 3 weeks of every 4 week cycle (i.e., on Days 1, 8 and 15).
  • ASG-22CE
Part B ASG-22CE Cisplatin Therapy-Ineligible ExpansionExperimentalSubjects will receive a single 30 minute IV infusion of ASG-22CE at a dose one level below 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.
  • ASG-22CE
Part B ASG-22CE Non Small Cell Lung Cancer ExpansionExperimentalSubjects will receive a single 30 minute IV infusion of ASG-22CE 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.
  • ASG-22CE
Part B ASG-22CE Ovarian Cancer ExpansionExperimentalSubjects will receive a single 30 minute IV infusion of ASG-22CE 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.
  • ASG-22CE
Part C ASG22CE Immune Checkpooint Inhibitor (CPI) Treated ExpaExperimentalSubjects will receive a single 30 minute IV infusion of ASG-22CE 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 ASG22CE, Investigator decision or consent withdrawal.
  • ASG-22CE

Eligibility Criteria

Inclusion Criteria:

- Dose Escalation, Cis-ineligible and CPI-Treated Expansion cohorts: Subjects must have 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: Subjects must have histologic or cytologic diagnosis of NSCLC (squamous or non-squamous or NSCLC-not specified)

- For Dose Escalation, Cis-ineligible and CPI-Treated Expansion Cohorts, subjects must submit a tumor tissue for Nectin-4 expression; however, the results are not required for enrollment.

- For the NSCLC and Ovarian Expansion Cohorts: 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 Cis-ineligible Expansion Cohort: Subject must not have received any prior lines of chemotherapy (prior treatment with immunotherapy is allowed).

- 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)

- For Dose Escalation, NSCLC, Ovarian, and CPI Treated Expansion Cohorts: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- For the Cis-ineligible expansion Cohort: Subject must have an ECOG performance status of ≤ 2

- 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 ASG-22CE):

- 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: serum creatinine ≤ 2.0 mg/dL, or measured 24 hour creatinine clearance of ≥ 45 mL/min. For Cis-ineligible Expansion Cohort: creatinine clearance estimate ≥15 ml/min and <60 ml/min by Cockcroft-Gault equation adjusted for body weight

- 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 weeks 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

- 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 Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome (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 ASG-22CE

- Major surgery within 28 days prior to first dose of study drug

- History of a primary invasive malignancy not listed in the inclusion criteria, which has not been in remission for at least 3 years. The following are exempt from the 3 year limit:

- non-melanoma skin cancer;

- adenocarcinoma of the prostate that has been surgically treated with a post-treatment Prostate Specific Antigen (PSA) that is undetectable;

- cervical carcinoma in situ on biopsy or squamous intraepithelial lesion on Pap smear; and

- definitively treated, stage I/II ER positive breast cancer; and

- epithelial ovarian tumors of low malignant potential

- History of uncontrolled diabetes mellitus or diabetic neuropathy within 3 months of the first dose of study drug

- Active infection requiring treatment ≤7 days before dose of study drug

- 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

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:up to 36 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of Anti-Drug Antibody (ADA)
Time Frame:up to 24 months
Safety Issue:
Description:
Measure:Tumor response
Time Frame:up to 24 months
Safety Issue:
Description: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
Measure:Objective response rate
Time Frame:up to 24 months
Safety Issue:
Description: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.
Measure:Disease control rate
Time Frame:up to 24 months
Safety Issue:
Description:Defined as the percentage of subjects who experience a best response of CR, PR or stable disease (SD)
Measure:Progression Free Survival (PFS)
Time Frame:36 months
Safety Issue:
Description:Time from the date of first infusion to the earliest date of documented disease progression per radiological evidence or death from any cause
Measure:Overall Survival
Time Frame:36 months
Safety Issue:
Description:Time from the date of first infusion until the date of death from any cause.
Measure:Duration of Response
Time Frame:36 months
Safety Issue:
Description: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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Agensys, Inc.

Trial Keywords

  • Metastatic Urothelial Cancer
  • Safety
  • AGS-22C3E
  • Nectin 4 protein, humans
  • Clinical Trial, Phase 1
  • ASG-22CE
  • ASG-22ME
  • Pharmacokinetics of ASG-22CE

Last Updated

November 15, 2016