Cabozantinib in Combination With Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Cancer

NCT04878029 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00002329NCI-2021-01365WINSHIP5259-21P30CA138292
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/Ib trial seeks to find out the best dose, possible benefits and/or side effects of cabozantinib in combination with enfortumab vedotin in treating urothelial cancer that has spread to nearby tissues and lymph nodes (locally advanced) or other parts of the body (metastatic). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to a toxic agent called vedotin. Enfortumab attaches to nectin-4 tumor cells in a targeted way and delivers vedotin to kill them. Cabozantinib in combination with enfortumab vedotin may be safe and effective in treating locally advanced or metastatic urothelial cancer.

Conditions

Infiltrating Bladder Urothelial Carcinoma With Squamous Differentiation; Metastatic Urothelial Carcinoma; Unresectable Urothelial Carcinoma; Locally Advanced Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Will be assessed by the Common Terminology Criteria for Adverse Events version 5.0.

  Up to study completion (estimated 5 years)

Secondary Outcomes (4)

• Objective response rate

  Through study completion, an average of 1 year

• Progression-free survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

• Overall survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

• Disease control rate (DCR)

  Up to study completion (estimated 5 years)

Other Outcomes (5)

• Maximum Plasma Concentration [Cmax]

  Up to study completion (estimated 5 years)

• Biomarker analysis

  Up to study completion (estimated 5 years)

• Quality of life assessment

  Through study completion, an average of 1 year

Study Arms (1)

Treatment (cabozantinib, enfortumab vedotin)

EXPERIMENTAL

Patients receive cabozantinib PO QD on days 1-28 and enfortumab vedotin IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib S-malate; Drug: Enfortumab Vedotin; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Cabozantinib S-malate DRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL-184, XL184

Treatment (cabozantinib, enfortumab vedotin)

Enfortumab Vedotin DRUG

Given IV

Also known as: AGS 22ME, AGS-22M6E, Anti-Nectin 4 ADC ASG-22CE, Anti-nectin-4 Monoclonal Antibody-Drug Conjugate AGS-22M6E, ASG-22CE, Enfortumab Vedotin-ejfv, Padcev

Treatment (cabozantinib, enfortumab vedotin)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (cabozantinib, enfortumab vedotin)

Questionnaire Administration OTHER

Ancillary studies

Treatment (cabozantinib, enfortumab vedotin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-documented urothelial carcinoma (squamous differentiation or mixed cell types allowed if urothelial carcinoma is present)
• Metastatic disease or unresectable locally-advanced disease
• Must have received prior treatment with a checkpoint inhibitor (CPI). A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor alone or with any other combination
• Must either have prior treatment with platinum-containing chemotherapy or be ineligible at time of enrollment
• Recovery to baseline or =\< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
• Tumor tissue samples must be available for submission prior to initiation of study treatment or patient must be willing to undergo repeat tumor biopsy
• Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1)
• An Eastern Cooperative Oncology Group (ECOG) performance status score of =\< 2
• Must be \>= 18 years of age
• Absolute neutrophil count (ANC) \>= 1500/uL without granulocyte colony-stimulating factor support (within 28 days before first dose of study treatment)
• White blood cell count \>= 2500/uL (within 28 days before first dose of study treatment)
• Platelets \>= 100,000/uL without transfusion (within 28 days before first dose of study treatment)
• Hemoglobin \>= 9 g/dL (within 28 days before first dose of study treatment)
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) =\< 3 x upper limit of normal (ULN). ALP =\< 5 x ULN with documented bone metastases (within 28 days before first dose of study treatment)
• Total bilirubin =\< 1.5 x ULN (for subjects with Gilbert's disease =\< 3 x ULN) (within 28 days before first dose of study treatment)

You may not qualify if:

• Prior treatment with cabozantinib
• Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs)
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 2 weeks before first dose of study treatment
• Radiation therapy within 2 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment
• Subjects with a diagnosis of incidental, subsegmental pulmonary embolism (PE) or deep venous thrombosis (DVT) within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation for at least 1 week before first dose of study treatment

Sponsors & Collaborators

• Emory University: lead
• Exelixis: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

cabozantinib; enfortumab vedotin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Mehmet A Bilen, MD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mehmet Bilen, MD

CONTACT

404-778-3448; mbilen@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: May 7, 2021
• Study Start: July 23, 2021
• Primary Completion (Estimated): November 13, 2027
• Study Completion (Estimated): December 21, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

US (1)