NCT04225117

Brief Summary

The primary purpose of this study is to determine the antitumor activity of enfortumab vedotin as measured by confirmed objective response rate (ORR) per RECIST v1.1. This study will also assess other measures of antitumor activity; overall survival (OS); as well as the safety and tolerability of enfortumab vedotin for cohorts 1 to 8 and enfortumab vedotin + pembrolizumab in cohort 9.

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
329

participants targeted

Target at P75+ for phase_2

Timeline
5mo left

Started Mar 2020

Longer than P75 for phase_2

Geographic Reach
3 countries

39 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress94%
Mar 2020Sep 2026

First Submitted

Initial submission to the registry

January 9, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 13, 2020

Completed
2 months until next milestone

Study Start

First participant enrolled

March 10, 2020

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 25, 2025

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

April 13, 2026

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2026

Expected
Last Updated

April 13, 2026

Status Verified

March 1, 2026

Enrollment Period

5 years

First QC Date

January 9, 2020

Results QC Date

February 24, 2026

Last Update Submit

March 24, 2026

Conditions

Keywords

Squamous NSCLCTriple negative breast cancer (TNBC)ASG-22CEnon-small cell lung cancer (NSCLC)Hormone receptor-positive/ human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancernon-squamous NSCLClocally advanced or metastatic malignant solid tumorsHead and neck cancerEV-202Gastric or gastroesophageal junction (GEJ) or esophageal cancer

Outcome Measures

Primary Outcomes (2)

  • Cohorts 1-8: Confirmed Overall Response Rate (ORR) (Complete Response [CR] and Partial Response [PR]) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (V)1.1 Per Investigator Assessment

    Confirmed ORR was defined as the percentage of participants whose objective response was confirmed as CR or PR according to RECIST V1.1 per investigator assessment, using exact method based on binomial distribution (Clopper-Pearson).

    Up to 20.04 months

  • Cohort 9: Confirmed ORR (CR and PR) Per RECIST V1.1 Per Investigator Assessment

    Confirmed ORR was defined as the percentage of participants whose objective response was confirmed as CR or PR according to RECIST V1.1 per investigator assessment, using exact method based on binomial distribution (Clopper-Pearson).

    Up to 12.85 months

Secondary Outcomes (10)

  • Cohorts 1-8: Duration of Resonse (DOR) Per RECIST V.1.1 Per Investigator Assessment

    Up to 20.04 months

  • Cohorts 1-8: Disease Control Rate (DCR) Per RECIST V1.1 Per Investigator Assessment

    Up to 22 months

  • Cohorts 1-8: Progression Free Survival (PFS) Per RECIST V1.1 Per Investigator Assessment

    Up to 22 months

  • Cohorts 1-8: Overall Survival (OS)

    Up to 34 months

  • Cohorts 1-8: Number of Participants With Treatment-emergent Adverse Events (AEs)

    Up to end of treatment + 30 days (32 months)

  • +5 more secondary outcomes

Study Arms (9)

Cohort 1: HR+/HER2- breast cancer

EXPERIMENTAL

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. HR+/HER2- = Hormone receptor-positive/ human epidermal growth factor receptor 2-negative

Drug: enfortumab vedotin

Cohort 2: Triple negative breast cancer (TNBC)

EXPERIMENTAL

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Drug: enfortumab vedotin

Cohort 3: Squamous non-small cell lung cancer

EXPERIMENTAL

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Drug: enfortumab vedotin

Cohort 4: Non-squamous non-small cell lung cancer

EXPERIMENTAL

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Drug: enfortumab vedotin

Cohort 5: Head and neck cancer

EXPERIMENTAL

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Drug: enfortumab vedotin

Cohort 6: Gastric or GEJ or esophageal cancer

EXPERIMENTAL

Participants enrolled into Cohort 6 will be reallocated based on disease type and histology into Cohorts 7 or 8. GEJ= gastroesophageal junction

Drug: enfortumab vedotin

Cohort 7: Gastric and esophageal adenocarcinoma (EAC) including GEJ adenocarcinoma

EXPERIMENTAL

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Drug: enfortumab vedotin

Cohort 8: Esophageal squamous cell carcinoma (ESCC)

EXPERIMENTAL

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Drug: enfortumab vedotin

Cohort 9: Head and neck squamous cell carcinoma (HNSCC)

EXPERIMENTAL

Participants will receive enfortumab vedotin as an IV infusion on days 1 and 8 of each 21-day cycle. Pembrolizumab will be administered as an IV infusion on day 1 of each 21-day cycle.

Drug: enfortumab vedotinDrug: pembrolizumab

Interventions

IV infusion

Also known as: KEYTRUDA®
Cohort 9: Head and neck squamous cell carcinoma (HNSCC)

intravenous (IV) infusion

Also known as: ASG-22CE
Cohort 1: HR+/HER2- breast cancerCohort 2: Triple negative breast cancer (TNBC)Cohort 3: Squamous non-small cell lung cancerCohort 4: Non-squamous non-small cell lung cancerCohort 5: Head and neck cancerCohort 6: Gastric or GEJ or esophageal cancerCohort 7: Gastric and esophageal adenocarcinoma (EAC) including GEJ adenocarcinomaCohort 8: Esophageal squamous cell carcinoma (ESCC)Cohort 9: Head and neck squamous cell carcinoma (HNSCC)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subject is considered an adult according to local regulation at the time of signing the informed consent form (ICF).
  • Subject has measurable disease by RECIST Version 1.1.
  • Subject has accessible archival tumor tissue from either the primary tumor or a metastatic site, for which source and availability have been confirmed prior to study treatment. If no archival tumor tissue is available, the subject will have a biopsy to obtain tumor tissue prior to study treatment. If the subject is unable to undergo a biopsy due to safety concerns, enrollment into the study must be discussed with the medical monitor.
  • For cohort 9 only: Subject should submit archival or fresh tumor tissue sample for programmed cell death-ligand 1 (PD-L1) central testing during screening if no local PD-L1 test result is available. Central test result for PD-L1 will be required prior to subject enrollment. For cohort 9 subjects with local PD-L1 test result confirming CPS ≥ 1, archival or fresh tissue sample for exploratory analysis should be submitted within 5 days of enrollment.
  • Subject has ECOG performance status of 0 or 1.
  • Subject has the following baseline laboratory data. If a subject has received a recent blood transfusion, the hematology tests must be obtained ≥ 28 days after any blood transfusion.
  • absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L
  • platelet count ≥ 100 × 10\^9/L
  • hemoglobin ≥ 9 g/dL
  • serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease
  • creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards or as measured by 24-hour urine collection (glomerular filtration rate \[GFR\] can also be used instead of CrCl).
  • alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
  • Subject agrees not to participate in another interventional study while receiving study treatment in the present study.
  • Additional contraceptive requirements exist for male and female subjects.
  • Evidence of progression on or after the last regimen received.
  • +64 more criteria

You may not qualify if:

  • For All Cohorts:
  • Subject has preexisting sensory or motor neuropathy Grade ≥ 2.
  • Subject has active central nervous system (CNS) metastases. Subjects with treated CNS metastases are permitted on study if all the following are true:
  • CNS metastases have been clinically stable for ≥ 6 weeks prior to screening
  • If requiring steroid treatment for CNS metastases, the subject is on a stable dose ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks
  • Baseline imaging scans show no evidence of new or enlarged brain metastasis
  • Subject does not have leptomeningeal disease
  • Subject has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).
  • Subjects with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or panhypopituitarism are excluded. Subjects with ongoing immunotherapy-related colitis, uveitis, myocarditis or pneumonitis, or subjects with other immunotherapy-related AEs requiring high doses of steroids (\> 20 mg/day of prednisone or equivalent), are excluded. Subject with ≤ Grade 2 immunotherapy-related hypothyroidism or panhypopituitarism may be enrolled when well maintained/controlled on a stable dose of hormone replacement therapy (if indicated).
  • Subject has a history of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Uncontrolled diabetes (within 3 months before first dose) is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c between 7 and \< 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained. The lowest HbA1c during the screening period will be used to determine eligibility.
  • Subject has prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE) based antibody-drug conjugates (ADCs).
  • Subject has a second malignancy diagnosed within 3 years before first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Subjects with non-melanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
  • Subject is currently receiving systemic antimicrobial treatment for viral, bacterial, or fungal infection at the time of first dose of study treatment. Routine antimicrobial prophylaxis is permitted.
  • Subject has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or active hepatitis C (e.g., hepatitis C virus \[HCV\] RNA \[qualitative\] is detected).
  • Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or 2).
  • +22 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (39)

Arizona Oncology

Tucson, Arizona, 85711, United States

Location

University of California - San Francisco

San Francisco, California, 94158, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Florida Cancer Specialists

Tallahassee, Florida, 32308, United States

Location

Florida Cancer Specialists

West Palm Beach, Florida, 33401, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30318, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Northwestern University Medical Center

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Kansas

Fairway, Kansas, 66205, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10022, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Gettysburg Cancer Center

Gettysburg, Pennsylvania, 17375, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Research Center

Dallas, Texas, 75230, United States

Location

University of Texas

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Site CA15003

Ottawa, Ontario, K1H 8L6, Canada

Location

Site JP81004

Nagoya, Aichi-ken, Japan

Location

Site JP81001

Kashiwa, Chiba, Japan

Location

Site JP81005

Chuo-ku, Osaka, Japan

Location

Site JP81007

Ōsaka-sayama, Osaka, Japan

Location

Site JP81011

Kitaadachi-Gun, Saitama, Japan

Location

Site JP81006

Nakatogari, Shizuoka, Japan

Location

Site JP81003

Chūō, Tokyo, Japan

Location

Site JP81002

Koto, Tokyo, Japan

Location

Site JP81010

Okayama, Japan

Location

Related Publications (3)

  • Muro K, Feinstein T, Baranda J, Bonta I, Yanagitani N, Gersten T, Gandhi L, Kudo T, Fujioka N, Kaplan J, Gorla S, Liu S, Wozniak M, Poondru S, Dillon R, Meng C, Patil T. Enfortumab vedotin in patients with advanced non-small cell lung cancer after disease progression on platinum- and PD-1/PD-L1 inhibitor-containing regimens: Phase 2 international multicenter EV-202 study. Eur J Cancer. 2025 Sep 9;227:115603. doi: 10.1016/j.ejca.2025.115603. Epub 2025 Jul 9.

  • Swiecicki PL, Yilmaz E, Rosenberg AJ, Fujisawa T, Bruce JY, Meng C, Wozniak M, Zhao Y, Mihm M, Kaplan J, Gorla S, Geiger JL. Phase II Trial of Enfortumab Vedotin in Patients With Previously Treated Advanced Head and Neck Cancer. J Clin Oncol. 2025 Feb 10;43(5):578-588. doi: 10.1200/JCO.24.00646. Epub 2024 Oct 31.

  • Muro K, Chin K, Maron SB, Braiteh FS, Mitani S, Hara H, Kuboki Y, Mulcahy MF, Baranda JC, Gardner FP, Jin N, Hamauchi S, Kaplan J, Gorla S, Liu S, Wozniak M, Poondru S, Dillon R, Meng C, Kondo S. Phase II trial of enfortumab vedotin in patients with previously treated gastric and esophageal cancers. ESMO Open. 2025 Nov;10(11):105806. doi: 10.1016/j.esmoop.2025.105806. Epub 2025 Oct 23.

MeSH Terms

Conditions

Triple Negative Breast NeoplasmsCarcinoma, Non-Small-Cell LungBreast NeoplasmsHead and Neck NeoplasmsEsophageal Neoplasms

Interventions

enfortumab vedotinpembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Results Point of Contact

Title
Clinical Transparency
Organization
Astellas Pharma Global Development, Inc

Study Officials

  • Medical Director

    Astellas Pharma Global Development, Inc.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 9, 2020

First Posted

January 13, 2020

Study Start

March 10, 2020

Primary Completion

February 25, 2025

Study Completion (Estimated)

September 30, 2026

Last Updated

April 13, 2026

Results First Posted

April 13, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
More information

Locations