Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion
Terence Friedlander

Description

Summary

This study will test an experimental drug (enfortumab vedotin) with different combinations of pembrolizumab and/or chemotherapy. Pembrolizumab is an immune checkpoint inhibitor (CPI) that is used to treat patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body. This study will have different parts to look at the side effects of (1) enfortumab vedotin with pembrolizumab, (2) enfortumab vedotin with chemotherapy, and (3) enfortumab vedotin with pembrolizumab and chemotherapy. A side effect is a response to a drug that is not part of the treatment effect. This study will also test if the cancer shrinks with the different treatment combinations.

Official Title

A Dose-escalation and Dose-expansion Study of Enfortumab Vedotin (ASG-22CE) in Combination With Pembrolizumab and/or Chemotherapy for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer

Details

This study will examine the safety and anticancer activity of enfortumab vedotin given intravenously in combination with pembrolizumab and/or chemotherapy to patients with locally advanced or metastatic urothelial cancer. The primary goal of the study is to determine the safety and tolerability of enfortumab vedotin in combination with pembrolizumab and/or chemotherapy. The study will be conducted in multiple parts: dose escalation (enfortumab vedotin + pembrolizumab) and dose expansion (cohorts of enfortumab vedotin + pembrolizumab and/or chemotherapy).

Keywords

Carcinoma, Transitional Cell Urinary Bladder Neoplasms Urologic Neoplasms Renal Pelvis Neoplasms Urothelial Cancer Ureteral Neoplasms Urethral Neoplasms ASG-22ME ASG-22CE Antibody-drug conjugate Antineoplastic agents CPI Enfortumab vedotin Locally advanced urothelial cancer Cisplatin Drug therapy Carboplatin Metastatic urothelial cancer Nectin-4 Gemcitabine Checkpoint Inhibitors Pembrolizumab Neoplasms Pelvic Neoplasms Dose Escalation: Enfortumab Vedotin + Pembrolizumab

Eligibility

You can join if…

Open to people ages 18 years and up

  • Histologically documented locally advanced or metastatic urothelial carcinoma (la/mUC), including squamous differentiation or mixed cell types.
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2.
  • Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, and G)
  • Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy and no prior treatment for la/mUC, or have disease progression following at least 1 platinum-containing treatment.
  • Cohort A: Ineligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
  • Cohort B: Must have disease progression during/following treatment with at least 1 platinum-containing regimen for la/mUC or disease recurrence.
  • Cohort D: Eligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
  • Cohort E: Ineligible for cisplatin-based chemotherapy, eligible for carboplatin, and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
  • Cohort F: Ineligible for platinum-based chemotherapy, or disease progression during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine.
  • Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.

You CAN'T join if...

  • Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2 inhibitor, except Cohort F.
  • Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonists, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F).
  • Ongoing sensory or motor neuropathy Grade 2 or higher.
  • Active central nervous system (CNS) metastases.
  • Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery).
  • Conditions requiring high doses of steroids or other immunosuppressive medications
  • Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
  • Uncontrolled diabetes mellitus

Locations

  • University of California at San Francisco accepting new patients
    San Francisco California 94134 United States
  • Stanford Cancer Center / Blood & Marrow Transplant Program accepting new patients
    Stanford California 94305 United States

Lead Scientist

  • Terence Friedlander
    I am a clinical and translational oncologist specializing in cancers of the genitourinary tract, specifically bladder and prostate cancers. My research is focused on understanding the basic biology these malignancies and in developing novel therapeutic ways to treat disease.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Astellas Pharma Global Development, Inc.
ID
NCT03288545
Phase
Phase 1
Study Type
Interventional
Last Updated