Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer After Failure of Platinum-Based Regimen or Anti-PD-1/ PD-L1 Based Immunotherapy

This is an international, multi-center, open-label, phase II study in patients with metastatic urothelial cancer after failure of platinum-based regimen or anti-PD-1 / PD-L1 based immunotherapy.

The primary objective is Objective Response Rate (ORR) based on central review.

The secondary objectives are Duration of Response (DOR) and Progression Free Survival (PFS) both based on central review and Overall Survival (OS).

Patients will receive IMMU-132 10 mg/kg administered intravenously on Days 1 and 8 of a 21-day cycle to be continued in the absence of unacceptable toxicity or progression of disease requiring termination of further treatment. Enrollment is expected to be completed in approximately 8 months. After discontinuation of treatment, patients will have a 30-day safety follow-up after last dose and then will be followed every 12 weeks for survival for a minimum of 2 years.

Inclusion Criteria:

• Patients with histologically confirmed urothelial cancer.
• ECOG Performance status score of 0 or 1.
• Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):
  1. Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;
  2. Or received adjuvant platinum-containing therapy following cystectomy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.
• Cohort 1: In addition to above criterion, must have had progression or recurrence of urothelial cancer following receipt of an anti-PD-1 /PD-L1 therapy.
• Cohort 2: Were ineligible for cisplatin-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease after an anti-PD-1/PD-L1 therapy.
• Adequate hematology, chemistry renal and hepatic function and coagulation values without ongoing transfusional.
• Subjects must have a 3-month life expectancy.
• Have measurable disease by CT or MRI as per RECIST 1.1 criteria.

Exclusion Criteria:

• Women who are pregnant or lactating.
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to the first dose of trial treatment.
• Has a diagnosis of immunodeficiency.
• Has had prior irinotecan therapy.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Requires concomitant medication interfering with ABCA1 transporter or UGT1A1
• Subjects with Gilbert's disease.
• Has a known additional malignancy that is progressing or requires active treatment.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has active cardiac disease, Myocardial infarction or unstable angina pectoris within 6 months of the first date of study therapy.
• Has active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) and subjects with a history of bowel obstruction.
• Has prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of enrollment.
• Must be at least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids ≤ 20 mg prednisone or equivalent daily are permitted provided the dose is stable for 4 weeks).
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus, Hepatitis B or Hepatitis C
• Has other concurrent medical or psychiatric conditions