Study of EV for Recurrent Endometrial Carcinoma

NCT07139977 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00055484
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is testing a drug called enfortumab vedotin in up to 12 patients with advanced endometrial (uterine) cancer that has worsened after previous treatments, including immunotherapy. The goal is to see how well the drug works and how safe it is. Patients will be treated for up to one year and followed over time to monitor their health and response to the treatment.

Conditions

Endometrial Cancer

Keywords

endometrial cancer; endometrioid; serous endometrial carcinoma

Outcome Measures

Primary Outcomes (2)

• Estimate the overall response rate (ORR)

  Overall response rate (ORR) of enfortumab vedotin treatment for patients with endometrioid or serous endometrial cancer, i.e., proportion of patients with a complete or partial response as per RECIST v1.1.

  24 months

• Evaluate the safety of enfortumab vedotin treatment

  Incidence of adverse events (AEs) and serious adverse event (SAEs) as defined by NCI CTCAE v5.

  24 months

Secondary Outcomes (4)

• Characterize the Duration of Response (DOR)

  30 months

• Estimate overall survival (OS)

  24 months

• Estimate progression-free survival (PFS)

  12 months

• Duration of response (DOR) by MMR status.

  30 months

Study Arms (1)

Enfortumab vedotin: 1.25 mg/kg on days 1,8, and 15 of the 28 day cycle

EXPERIMENTAL

Single arm trial

Drug: Enfortumab Vedotin

Interventions

Enfortumab Vedotin DRUG

Enfortumab vedotin is an ADC comprised of a fully human IgG1Κ antibody conjugated to the microtubule-disrupting agent MMAE via a protease-cleavable linker. Enfortumab vedotin is thought to induce anti-tumor activity by binding to the nectin-4 protein on the surface of cancer cells, leading to internalization, proteolytic cleavage of the linker, and intracellular release of MMAE that subsequently disrupts tubulin polymerization and leads to mitotic arrest and apoptosis of the tumor cell.

Enfortumab vedotin: 1.25 mg/kg on days 1,8, and 15 of the 28 day cycle

Eligibility Criteria

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

You may qualify if:

• Female patient of age ≥18 years.
• Recurrent and progressive endometrial cancer, all stages at primary diagnosis. The histology types will be pending the preclinical assessments, but can include:
• Endometrioid endometrial carcinoma
• Serous endometrial carcinoma
• Prior standard of care of surgical intervention, including hysterectomy.
• Evidence of disease progression on or following the most recent line of therapy prior to screening. Therapy must include platinum-based chemotherapy. If the patient is eligible for immunotherapy, this must have been provided. Patient may have received either radiation therapy or hormone therapy, neither of which will be considered a line of therapy. Chemotherapy during radiotherapy will not be considered a line of therapy.
• Maximum of three prior lines of therapy. Neo-adjuvant and postsurgical therapy, if provided, will be counted as 1 line of therapy. Therapy given in a maintenance fashion after primary treatment will not be counted as a line of therapy.
• IHC expression of nectin-4.
• Toxicity from prior treatment recovered to G1 or G0.
• ECOG status of 1 or 0.
• At least 1 measurable target lesion according to RECIST v1.1, including the following criteria:
• Non-nodal lesion that measures ≥ 1.0 cm in the longest diameter.
• Lymph node (LN) lesion that measures as ≥ 1.5 cm in the short axis.
• The lesion is suitable for repeat measurement using computed tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of subsequent growth after treatment.
• Documented tumor status for MSI and MMR.

You may not qualify if:

• Diagnosis of endometrial sarcoma (leiomyosarcoma, endometrial stromal sarcoma, high-grade sarcoma).
• Diagnosis of non-endometrioid and non-serous endometrial cancer. Mixed tumors involving histologic types other than serous and endometrioid will not be eligible.
• Tumor sample does not express nectin-4 (local IHC testing).
• Symptomatic CNS metastases or leptomeningeal metastases. Patients with symptomatic brain metastasis must be treated and must be stable for at least 4 weeks prior to study treatment.
• Active second malignancy with anti-cancer treatments (except for treated in-situ carcinomas \[e.g., breast, cervix, bladder\], or basal or squamous cell carcinoma of the skin) within the past 24 months.
• Sensory or motor neuropathy ≥ G2
• Prior history of significant cardiovascular impairment within 12 months of the first dose of study drug: such as history of congestive heart failure greater than New York Heart Association (NYHA)Class II, unstable angina, myocardial infarction, or cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability.
• Active infection requiring systemic IV antibiotics within 14 days, or oral antibiotics within 7 days, prior to administration of study drugs. Regular treatment of urinary tract infection (UTI) and/or topical treatment are allowed.
• Uncontrolled diabetes defined as HgbA1c of ≥ 8%.
• Hepatitis B, C, or HIV infection.
• Have not recovered to CTCAE v5.0 Grade 0 or 1 (except chemotherapy related grade 2 peripheral neuropathy, or grade 2 endocrinopathy with adequate replacement therapy) from any toxicity and/or complications from major surgery or prior cancer therapeutics before starting therapy.
• Ongoing treatment for EC, including radiation therapy, hormonal therapy, chemotherapy, immunotherapy, or any investigational therapy, unless they have been discontinued at least 4 weeks prior to screening and there is no plan to re-initiate during the study. radiation therapy is allowed prior to and during study drug administration as long as there are no acute toxicities.
• Active intestinal obstruction.
• Known psychiatric or substance use disorders that would interfere with cooperation with the requirements of the trial.
• Any conditions that required systemic immunosuppression therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) within 7 days prior to the first dose of study drug.

Sponsors & Collaborators

• William Bradley: lead
• Astellas Pharma Inc: collaborator

Study Sites (1)

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

enfortumab vedotin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• William Bradley, MD

  Medical College of Wiscnson

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mastaneh Irani

CONTACT

4148056621; mairani@mcw.edu

Sukanya Skandarajah, Research Operations Manager

CONTACT

4148055337; sskandarajah@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Obstetrics and Gynecology

Study Record Dates

• First Submitted: August 18, 2025
• First Posted: August 24, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): May 31, 2028
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)