NCT04225117

A Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)

Active, enrolled Phase 2 Results posted Last updated 13 April 2026

What this trial tests

Phase 2 trial testing enfortumab vedotin in Locally Advanced or Metastatic Malignant Solid Tumors in 329 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

10 March 2020

Primary endpoint
25 February 2025

30 September 2026

Quick facts

Lead sponsor	Astellas Pharma Global Development, Inc.
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	329
Start date	10 March 2020
Primary completion	25 February 2025
Estimated completion	30 September 2026
Sites	39 locations across Japan, Canada, United States

Drugs / interventions tested

• enfortumab vedotin — full drug profile →
• pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Locally Advanced or Metastatic Malignant Solid Tumors — all drugs for Locally Advanced or Metastatic Malignant Solid Tumors →

Sponsor

Astellas Pharma Global Development, Inc. — full company profile →

Who can join

18 and older, any sex, with Locally Advanced or Metastatic Malignant Solid Tumors. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · Up to 20.04 months

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).

Group	Value	95% CI
Cohort 1: HR+/HER2- Breast Cancer	15.6	6.49 – 29.46
Cohort 2: TNBC Cancer	19.0	8.60 – 34.12
Cohort 3: Squamous NSCLC	4.3	0.11 – 21.95
Cohort 4: Non-squamous NSCLC	16.3	6.81 – 30.70
Cohort 5: Head and Neck Cancer	23.9	12.59 – 38.77
Cohort 7: EAC	9.5	2.66 – 22.62
Cohort 8: ESCC	18.2	8.19 – 32.71

Cohort 9: Confirmed ORR (CR and PR) Per RECIST V1.1 Per Investigator Assessment Primary · Up to 12.85 months

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).

Group	Value	95% CI
Cohort 9: HNSCC	39.0	24.20 – 55.50

Cohorts 1-8: Duration of Resonse (DOR) Per RECIST V.1.1 Per Investigator Assessment Secondary · Up to 20.04 months

DOR was defined as the time from the date of first documented response (CR or PR that is subsequently confirmed) to the date of first documented progressive disease (PD) per RECIST V1.1 or death due to any cause, whichever occurs first. DOR was only calculated for participants achieving a confirmed CR or PR, based on Kaplan-Meier estimate.

Group	Value	95% CI
Cohort 1: HR+/HER2- Breast Cancer	7.23	3.52 – 7.23
Cohort 2: TNBC Cancer	3.78	1.87 – 3.94
Cohort 3: Squamous NSCLC	3.71	NA – NA
Cohort 4: Non-squamous NSCLC	10.15	9.69 – 10.38
Cohort 5: Head and Neck Cancer	9.43	2.53 – NA
Cohort 7: EAC	10.32	1.64 – 10.32
Cohort 8: ESCC	3.88	2.33 – 7.39

Cohorts 1-8: Disease Control Rate (DCR) Per RECIST V1.1 Per Investigator Assessment Secondary · Up to 22 months

DCR was defined as the percentage of participants whose Best Overall Response (BOR) was confirmed CR or PR or stable disease (SD) (≥ 7 weeks).

Group	Value	95% CI
Cohort 1: HR+/HER2- Breast Cancer	51.1	35.77 – 66.30
Cohort 2: TNBC Cancer	57.1	40.96 – 72.28
Cohort 3: Squamous NSCLC	65.2	42.73 – 83.62
Cohort 4: Non-squamous NSCLC	67.4	51.46 – 80.92
Cohort 5: Head and Neck Cancer	56.5	41.11 – 71.07
Cohort 7: EAC	47.6	32.00 – 63.58
Cohort 8: ESCC	45.5	30.39 – 61.15

Cohorts 1-8: Progression Free Survival (PFS) Per RECIST V1.1 Per Investigator Assessment Secondary · Up to 22 months

PFS was defined as the time from start of study intervention to first documentation of objective tumor progression or death due to any cause, whichever comes first, based on Kaplan-Meier estimate.

Group	Value	95% CI
Cohort 1: HR+/HER2- Breast Cancer	5.39	3.35 – 5.68
Cohort 2: TNBC Cancer	3.52	2.10 – 4.63
Cohort 3: Squamous NSCLC	3.52	1.91 – 5.42
Cohort 4: Non-squamous NSCLC	4.11	2.76 – 5.72
Cohort 5: Head and Neck Cancer	3.94	2.79 – 4.67
Cohort 7: EAC	3.06	1.77 – 3.71
Cohort 8: ESCC	2.10	1.87 – 3.71

Cohorts 1-8: Number of Participants With Treatment-emergent Adverse Events (AEs) Secondary · Up to end of treatment + 30 days (32 months)

A TEAE is any untoward medical occurrence in a participant administered enfortumab vedotin, and which does not necessarily have to have a causal relationship with this treatment. A TEAE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of enfortumab vedotin whether or not considered related to the enfortumab vedotin. A TEAE is considered "serious" if the event: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the abi

TEAEs

Group	Value	95% CI
Cohort 1: HR+/HER2- Breast Cancer	45
Cohort 2: TNBC Cancer	42
Cohort 3: Squamous NSCLC	22
Cohort 4: Non-squamous NSCLC	42
Cohort 5: Head and Neck Cancer	45
Cohort 7: EAC	42
Cohort 8: ESCC	43

Serious TEAEs

Group	Value	95% CI
Cohort 1: HR+/HER2- Breast Cancer	12
Cohort 2: TNBC Cancer	9
Cohort 3: Squamous NSCLC	8
Cohort 4: Non-squamous NSCLC	16
Cohort 5: Head and Neck Cancer	22
Cohort 7: EAC	14
Cohort 8: ESCC	12

Cohort 9: DOR Per RECIST V.1.1 Per Investigator Assessment Secondary · Up to 12.85 months

DOR was defined as the time from the date of first documented response (CR or PR that is subsequently confirmed) to the date of first documented PD per RECIST V1.1 or death due to any cause, whichever occurs first. DOR was only calculated for participants achieving a confirmed CR or PR, based on Kaplan-Meier estimate.

Group	Value	95% CI
Cohort 9: HNSCC	NA	5.78 – NA

Cohort 9: DCR Per RECIST V1.1 Per Investigator Assessment Secondary · Up to 15 months

DCR was defined as the percentage of participants whose BOR is confirmed CR or PR or SD (≥ 7 weeks).

Group	Value	95% CI
Cohort 9: HNSCC	75.6	59.70 – 87.64

Cohort 9: PFS Per RECIST V1.1 by Investigator Assessment Secondary · Up to 15 months

PFS was defined as the time from start of study intervention to first documentation of objective tumor progression or death due to any cause, whichever comes first, based on Kaplan-Meier estimate.

Group	Value	95% CI
Cohort 9: HNSCC	5.06	3.45 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Cohorts 1-8: All-cause mortality: up to 34 months; AEs: up to end of treatment + 30 days (32 months). Cohort 9: All-cause mortality: up to 15 months; AEs: up to end of treatment + 30 days (15 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: HR+/HER2- Breast Cancer

Serious: 12/45 (27%)

Deaths: 36/45

Cohort 2: TNBC Cancer

Serious: 9/42 (21%)

Deaths: 30/42

Cohort 3: Squamous NSCLC

Serious: 8/23 (35%)

Deaths: 20/23

Cohort 4: Non-squamous NSCLC

Serious: 16/43 (37%)

Deaths: 33/45

Cohort 5: Head and Neck Cancer

Serious: 22/46 (48%)

Deaths: 38/46

Cohort 7: EAC

Serious: 14/42 (33%)

Deaths: 34/42

Cohort 8: ESCC

Serious: 12/44 (27%)

Deaths: 39/45

Cohort 9: HNSCC

Serious: 21/41 (51%)

Deaths: 10/41

Serious adverse events (135 terms)

Reaction	System	Cohort 1: HR+/HER2- Breast…	Cohort 2: TNBC Cancer	Cohort 3: Squamous NSCLC	Cohort 4: Non-squamous NSCLC	Cohort 5: Head and Neck Ca…	Cohort 7: EAC	Cohort 8: ESCC	Cohort 9: HNSCC
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—
Syncope	Nervous system disorders	—	—	—	—	—	—	—	—
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Disease progression	General disorders	—	—	—	—	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Haemoptysis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Pancytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—	—	—	—	—
Adrenocorticotropic hormone deficiency	Endocrine disorders	—	—	—	—	—	—	—	—

Other adverse events (100 terms — click to expand)

Reaction	System	Cohort 1: HR+/HER2- Breast…	Cohort 2: TNBC Cancer	Cohort 3: Squamous NSCLC	Cohort 4: Non-squamous NSCLC	Cohort 5: Head and Neck Ca…	Cohort 7: EAC	Cohort 8: ESCC	Cohort 9: HNSCC
Fatigue	General disorders	—	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Malaise	General disorders	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Dry eye	Eye disorders	—	—	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—
Eosinophilia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Lacrimation increased	Eye disorders	—	—	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—	—
Taste disorder	Nervous system disorders	—	—	—	—	—	—	—	—
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—	—	—	—	—

Most-reported serious reactions: Tumour haemorrhage, Syncope, Acute respiratory failure, Atrial fibrillation, Abdominal pain, Nausea, Vomiting, Disease progression.

Data from ClinicalTrials.gov NCT04225117 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Recent advances in therapeutic strategies for triple-negative breast cancer.
   Li Y, Zhang H, Merkher Y, Chen L, et al · · 2022 · cited 643× · PMID 36038913 · DOI 10.1186/s13045-022-01341-0
2. Triple negative breast cancer: Pitfalls and progress.
   Zagami P, Carey LA. · · 2022 · cited 546× · PMID 35987766 · DOI 10.1038/s41523-022-00468-0
3. Practical classification of triple-negative breast cancer: intratumoral heterogeneity, mechanisms of drug resistance, and novel therapies.
   Marra A, Trapani D, Viale G, Criscitiello C, et al · · 2020 · cited 209× · PMID 33088912 · DOI 10.1038/s41523-020-00197-2
4. Resistance to antibody-drug conjugates in breast cancer: mechanisms and solutions.
   Chen YF, Xu YY, Shao ZM, Yu KD. · · 2023 · cited 93× · PMID 36357174 · DOI 10.1002/cac2.12387
5. <i>NECTIN4</i> Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer.
   Klümper N, Tran NK, Zschäbitz S, Hahn O, et al · · 2024 · cited 92× · PMID 38657187 · DOI 10.1200/jco.23.01983
6. Antibody-drug conjugates in lung cancer: dawn of a new era?
   Coleman N, Yap TA, Heymach JV, Meric-Bernstam F, et al · · 2023 · cited 89× · PMID 36631624 · DOI 10.1038/s41698-022-00338-9
7. Triple-negative breast cancer: A run-through of features, classification and current therapies.
   Manjunath M, Choudhary B. · · 2021 · cited 76× · PMID 33986872 · DOI 10.3892/ol.2021.12773
8. Antibody-Drug Conjugates for the Treatment of Breast Cancer.
   Corti C, Giugliano F, Nicolò E, Ascione L, et al · · 2021 · cited 51× · PMID 34207890 · DOI 10.3390/cancers13122898