A study to find out if enfortumab vedotin given with pembrolizumab helps people with muscle-invasive bladder cancer keep their bladder.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astellas Pharma Global Development Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others

To evaluate: 1) the overall cCR rate after treatment with enfortumab vedotin in combination with pembrolizumab and 2) the 2-year BI-EFS rate in participants who had cCR

Secondary objectives 3

1. To evaluate: 1) the overall cCR rate after 4 cycles of treatment with enfortumab vedotin in combination with pembrolizumab, and 2) the 2-year BI-EFS rate in participants who had cCR after 4 cycles
2. To evaluate other measures of efficacy of enfortumab vedotin in combination with pembrolizumab in participants who had cCR.
3. To evaluate the safety and tolerability of enfortumab vedotin in combination with pembrolizumab.

Conditions and MedDRA coding

Muscle-invasive Bladder Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Participant is ≥ 18 years of age at the time of signing the ICF.
2. 2. Participant has histologically-confirmed MIBC, stage cT2–T4aN0M0 or T1-T4aN1M0.
3. 3. Participant has predominant UC histology (≥ 50%).
4. 4. Participant is deemed eligible for RC and PLND by a urologist and/or oncologist.
5. 5. Participant has accessible archival tumor tissue from the primary tumor, for which source and availability have been confirmed prior to study intervention. If no archival tumor tissue is available, the participant will have a biopsy to obtain tumor tissue prior to study intervention.
6. 6. Participant has ECOG performance status of 0 to 2.
7. 11. Have a TUR of a bladder tumor within 60 days (+14 days) prior to screening (from the date of ICF signature).

Exclusion criteria 13

1. 1. Participant has preexisting sensory or motor neuropathy Grade ≥ 2
2. 2. Participant has ≥ N2 disease or metastatic disease (M1) as identified by imaging.
3. 3. Participant has a history of uncontrolled diabetes mellitus within 3 months prior to screening. Uncontrolled diabetes (within 3 months before first dose) is defined as 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.
4. 4. Participant has a second malignancy diagnosed within 3 years before first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy. Participant 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.
5. 9. Participant has known active keratitis or corneal ulcerations. Participant with superficial punctate keratitis is allowed if the disorder is being adequately treated in the opinion of the investigator
6. 10. Participant has a history of (non-infectious) pneumonitis/ILD that required steroids or has current pneumonitis/ILD.
7. 11. Participant has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
8. 13. Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency."
9. 14. Participant has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
10. 15. Participant has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
11. 16. Participant has received prior systemic anti-cancer therapy for MIBC/NMIBC, or received prior systemic anti-cancer therapy including investigational agents (including enfortumab vedotin or other MMAE-based ADCs) within 3 years prior to screening
12. 18. Participant has received a partial cystectomy of the bladder to remove any NMIBC or MIBC.
13. 19. Participant has received any prior radiotherapy to the bladder.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall cCR rate after treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator (FAS) - 2-year BI-EFS rate after treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator (FAS1 analysis set)

Secondary endpoints 3

1. Overall cCR rate after 4 cycles of treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator (FAS) - 2-year BI-EFS rate after treatment with enfortumab vedotin in combination with pembrolizumab as assessed by investigator (FAS2 analysis set)
2. OS (FAS1 analysis set), DFS as assessed by investigator (FAS1 analysis set), MFS as assessed by investigator (FAS1 analysis set)
3. Type, incidence, relatedness, severity and seriousness of safety variables (AEs and laboratory tests), Treatment discontinuation rate due to AEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astellas Pharma Global Development Inc.

Sponsor organisation

Astellas Pharma Global Development Inc.

Address

2375 Waterview Drive

City

Northbrook

Postcode

60062-6145

Country

United States

Scientific contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Clinical Trial Unit Head

Public contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Clinical Trial Unit Head

Third parties 9

Locations

5 EU/EEA countries · 48 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 69 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications