Clinical Trial 17773

Cancer Type: Genitourinary
Interventions:ASG-22CE

Study Type: Treatment
Phase of Study: Phase I
Investigators:


    Overview

    Study 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

    Summary

    The first purpose of this study is to test the safety of the investigational medicine at different dose levels. Investigators want to find out what effects, good and/or bad, it has on the participant's type of cancer. The second purpose of this study is to measure the levels of the investigational medicine in the participant's blood at different times. The third purpose is to see whether the investigational medicine has any effect in the control of cancer.

    Objective

    To evaluate the safety and pharmacokinetics of ASG-22CE in subjects with metastatic urothelial cancer. To assess the immunogenicity and anti-tumor activity of ASG-22CE in subjects with metastatic urothelial cancer.

    Inclusion Criteria

  • 18 years of age or older
  • Participant must have: A.) Dose Escalation, Cis-ineligible,and Immune Checkpoint Inhibitor(CPI)-Treated Expansion Cohorts: Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Potential participants with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible. B.) Ovarian Expansion Cohort: Participants 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. C.) NSCLC Expansion Cohort: Histologic or cytologic diagnosis of NSCLC (squamous or non-squamous or NSCLC-not specified)
  • For Dose Escalation, Cis-ineligible and CPI-Treated expansion cohorts, participants must submit a tumor tissue for Nectin-4 expression; however, the results are not required for enrollment.
  • For the NSCLC and Ovarian Expansion Cohorts: Participants must have tumor tissue positive (IHC H-score ≥150) for Nectin-4 expression (as measured by a Sponsor designated central laboratory using primary or metastatic invasive tumor tissue). Results are required for enrollment.
  • For Dose Escalation, NSCLC and Ovarian Expansion Cohorts: Participant must have failed at least one prior chemotherapy regimen for metastatic disease (urothelial and bladder cancer patients are not required to have failed prior chemotherapy regimen if considered unfit for cisplatin-based chemotherapy (Galsky, et. al. 2011)).
  • For the Cis-ineligible Expansion Cohort: Participant must not have received any prior lines of chemotherapy (prior treatment with immunotherapy is allowed).
  • For the CPI-Treated Expansion Cohort: Participant must have received prior treatment. with a CPI in the metastatic setting.
  • 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 Cis-ineligible Expansion Cohort: ECOG performance status of ≤ 2
  • Life expectancy of ≥ 3 months as assessed by the investigator
  • Negative pregnancy test (women of childbearing potential)
  • Adequate hematologic function
  • Adequate renal function
  • Adequate hepatic function
  • Sexually active fertile participants, and their partners, must agree to use medically accepted double-barrier methods of contraception during the study and at least 6 weeks after termination of study therapy
  • Additional cohort specific criteria may apply

  • 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)
  • Potential participants 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 (ASG-22CE, histidine, trehalose dihydrate, and polysorbate 20)
  • 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; epithelial ovarian tumors of low malignant potential.
  • History of uncontrolled diabetes mellitus or diabetic neuropathy within 3 months of first dose of study drug Active infection requiring treatment ≤7 days before dose of study drug
  • Condition or situation which may put the participant at significant risk, may confound the study results, or may interfere significantly with participation in the study
  • Any medical, psychiatric, addictive or other kind of disorder which compromises the ability to give written informed consent and/or to comply with procedures
  • Ocular conditions such as: Active infection or corneal ulcer, Monocularity; History of corneal transplantation; Contact lens dependent (contact lens: contact lens: must be able to switch to glasses during study duration); Uncontrolled glaucoma (topical medications allowed); Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder.