Enfortumab Vedotin as Monotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer

NCT04754191 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCI137651
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, phase II umbrella trial assessing the anti-tumor activity of enfortumab alone and in combination with other anti-cancer agents in subjects with metastatic castration-resistant prostate cancer. The trial will open to enrollment in Cohort A, enfortumab monotherapy. Additional cohorts may be added as new drug combinations are identified.

Conditions

Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Proportion subjects achieving a protocol-defined response (as defined below):

  To assess the anti-tumor action of the study therapy in subjects with metastatic castrate-resistant prostate cancer, as represented by the proportion of subjects achieving one of the following outcomes: Objective response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; Confirmed conversion of circulating tumor cell count (CTC) to \<5/7.5 mL blood; Prostate Specific Antigen (PSA) decline ≥ 50% from baseline; or Stable disease ≥ 6 months per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST 1.1

  12 months

Study Arms (1)

Treatment: all patients

EXPERIMENTAL

Enfortumab will be administered in monotherapy on days 1, 8, and 15 as part of a 28-day cycle at 1.25 mg/kg up to 125 mg.

Drug: Enfortumab vedotin

Interventions

Enfortumab vedotin DRUG

Cohort A will be treated with enfortumab vedotin on a 28 day cycle for up to 12 months.

Treatment: all patients

Eligibility Criteria

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

You may qualify if:

• Male subject aged ≥ 18 years.
• Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology.
• Diagnosis of metastatic or locally advanced, inoperable disease that cannot be treated with definitive intent
• Castrate levels of testosterone as defined as \< 50 ng/dL (1.73 nmol/L).
• Prior treatment with at least three or more cycles of taxane therapy (docetaxel or cabazitaxel).
• Note: Docetaxel in the newly diagnosed metastatic setting and docetaxel rechallenge allowed.
• Prior treatment with at least one prior Novel Hormone Therapy (NHT), defined as second-generation antiandrogen therapies that include but are not limited to abiraterone acetate, enzalutamide, apalutamide, and darolutamide.
• Subject has received or refused therapies which have shown to improve overall survival and are recommended per National Comprehensive Cancer Network (NCCN) guidelines prior to enrollment in trial. Such agents include but are not limited to docetaxel, cabazitaxel, sipuleucel-T, olaparib, rucaparib, radium-223 and lutetium (177Lu) vipivotide tetraxetan depending on patient eligibility.
• Had disease progression on or after NHT prior to enrolling in the study.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Adequate organ function as defined as:
• Hematologic:
• White blood cell count (WBC) ≥ 2000/mm3
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3

You may not qualify if:

• Prior or concurrent malignancy (other than adenocarcinoma of the prostate). Note: Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial as approved by the Principal Investigator.
• The subject has an uncontrolled, significant intercurrent or recent illness that would preclude safe study participation.
• Clinically significant cardiovascular disease: myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (\> New York Heart Association Classification Class IIB) or a serious cardiac arrhythmia requiring medication.
• Known HIV infection with a detectable viral load at the time of screening. Note: Patients on effective antiretroviral therapy with an undetectable viral load at the time of screening are eligible for this trial.
• Known chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with a detectable viral load.
• Note: Patients with an undetectable HBV viral load are eligible. Patients with an undetectable HCV viral load are eligible.
• Live attenuated vaccinations within ≤ 4 weeks of the first study therapy and while on trial is prohibited.
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3).
• Subjects taking prohibited medications as described in Section 6.3. A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment.

Sponsors & Collaborators

• University of Utah: lead
• Astellas Pharma Inc: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

enfortumab vedotin

Study Officials

• Umang Swami, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2021
• First Posted: February 15, 2021
• Study Start: June 5, 2022
• Primary Completion: April 22, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)