Health Trials

Enfortumab Vedotin, Pembrolizumab and Quemliclustat for the Treatment of Unresectable Locally Advanced and Metastatic Urothelial Cancer

ConditionsLocally Advanced Bladder Urothelial CarcinomaLocally Advanced Renal Pelvis Urothelial CarcinomaLocally Advanced Ureter Urothelial CarcinomaMetastatic Bladder Giant Cell Urothelial CarcinomaMetastatic Renal Pelvis Urothelial CarcinomaMetastatic Ureter Urothelial CarcinomaStage IIIB Bladder Cancer AJCC v8Stage IV Bladder Cancer AJCC v8Stage IV Renal Pelvis Cancer AJCC v8Stage IV Ureter Cancer AJCC v8Unresectable Bladder Urothelial CarcinomaUnresectable Renal Pelvis Urothelial CarcinomaUnresectable Ureter Urothelial Carcinoma
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorFred Hutchinson Cancer Center

About this trial

This phase Ib/II trial tests the safety, side effects, and best dose of quemliclustat in combination with enfortumab vedotin and pembrolizumab, and to see how well the combination works for the treatment of bladder, renal pelvis, or ureter urothelial cancer that cannot be removed by surgery (unresectable), that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Quemliclustat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving quemliclustat in combination with enfortumab vedotin and pembrolizumab and may be safe, tolerable and/or effective in treating patients with unresectable locally advanced and metastatic urothelial cancer.

Eligibility criteria

Qualifiers

Participants must be at least 18 years of age on the day of signing informed consent. Participant (or legally authorized representative if applicable) provides written informed consent for trial

Participants must have previously untreated locally advanced or metastatic bladder cancer including bladder cancer [stage IIIB: T1-T4N2-3M0, stage IVa: T4bAnyNM0 or AnyTAnyNM1a, and stage IVB: AnyTAnyNM1b clinical stage per American Joint Commission on Cancer (AJCC)] or renal pelvis or ureter cancer [stage IV: T4Nx-0M0, AnyTN1-2M0, AnyTAnyNM1 clinical stage per AJCC]. Lymph node with ≥ 15 mm short axis or biopsy-positive for carcinoma will be considered pathologically enlarged and measurable

Participants must have either conventional urothelial carcinoma or urothelial carcinoma variants. A review of pathology by a local expert genitourinary (GU) pathologist is required to confirm the diagnosis. Any component (%) of non-conventional urothelial noted on tumor specimen is allowed for only histologic subtypes listed below in up to 20% of participants enrolled in this study.

Urothelial carcinoma with squamous differentiation

Disqualifiers

Participants who are receiving any other investigational agents or concurrent anticancer treatment. Participants must have adequate treatment washout period before treatment, defined as: Major surgery (≥ 4 weeks), palliative radiation therapy (≥ 1 weeks from completion of treatment if they have recovered from the acute toxic effect of radiotherapy), prior adjuvant immunotherapy (≥ 4 weeks)

Participants whose tumors have any % neuroendocrine or small cell histology, glandular neoplasms, urachal carcinomas, tumor of mullerian type, mesenchymal tumors or urothelial tract hematopoietic and lymphoid tumors

Participants considered to be medically unfit for EV-P regimen as per Investigator discretion

Participants with concurrent use of systemic steroids (within 10 days of enrollment), except for physiologic doses of systemic steroid replacement or local (topical, nasal, intraarticular or inhaled) steroid use

Trial design

Treatments tested in this trial

  • Quemliclustat
  • Biospecimen Collection
  • Computed Tomography
  • Enfortumab Vedotin
  • Magnetic Resonance Imaging
  • Pembrolizumab
  • Biopsy Procedure

Treatment groups

27 Participants
are divided into 1 treatment group

Sponsors and collaborators

Fred Hutchinson Cancer Center

Lead sponsor

Bench to Bedside (B2B)

Collaborator

Arcus Biosciences, Inc.

Collaborator

Source ClinicalTrials.gov