A clinical study of new treatments given with enfortumab vedotin and pembrolizumab in people with urothelial cancer (MK-3475-04D)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Feb 2026 → ongoing

Decision date (initial)

2026-02-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2025-522253-19-00

WHO UTN

U1111-1322-3713

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacogenetic, Pharmacodynamic, Pharmacogenomic, Therapy, Efficacy, Safety, Dose response

1. To evaluate the safety and tolerability of an investigational agent in combination with EV plus pembrolizumab.
2. To evaluate ORR per RECIST 1.1 by investigator assessment of an investigational agent in combination with EV plus pembrolizumab.

Secondary objectives 2

1. To evaluate DOR per RECIST 1.1 by investigator assessment with an investigational agent in combination with EV plus pembrolizumab.
2. To characterize the PK profile of the investigational agent and EV when administered in combination.

Conditions and MedDRA coding

Urothelial carcinoma

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Has histologically documented urothelial carcinoma (UC) that is locally advanced and unresectable or metastatic
2. Must provide a newly obtained or archival tumor tissue sample (core or excisional biopsy)
3. Must not have received prior systemic therapy for locally advanced or metastatic UC
4. If infected with Human Immunodeficiency Virus (HIV), has well controlled HIV on antiretroviral therapy
5. If positive for hepatitis B surface antigen, has received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and has undetectable HBV viral load before randomization
6. If participant has a history of hepatitis C virus (HCV), has undetectable HCV viral load before randomization

Exclusion criteria 14

1. Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing
2. Has active keratitis or corneal ulcerations
3. Has active inflammatory bowel disease requiring immunosuppressive medication, or previous history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea)
4. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within the 6 months preceding study intervention
5. Has a history of uncontrolled diabetes
6. Has pleural effusion, ascites, and/or pericardial effusion that are symptomatic or require repeated drainage
7. Has active autoimmune disease that has required systemic treatment in the past 2 years
8. Has known additional malignancy that is progressing or has required active treatment within the past 2 years
9. Has known active central nervous system metastases and/or carcinomatous meningitis
10. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids, or has current pneumonitis/interstitial lung disease
11. Has an active infection requiring systemic therapy
12. If infected with HIV, has a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
13. Has concurrent active HBV and HCV infection
14. Has a history of stem cell/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Number of Participants Who Experienced At Least One Adverse Event (AE)
2. Number of Participants with Dose-limiting Toxicities
3. Number of Participants Who Discontinued Study Treatment Due to an AE
4. Objective Response Rate (ORR) as Assessed by Investigator

Secondary endpoints 13

1. Duration of Response (DOR) as Assessed by Investigator
2. Serum Maximum Concentration (Cmax) of MK-3120 Antibody-Drug Conjugate (ADC)
3. Serum Trough Concentration (Ctrough) of MK-3120 ADC
4. Serum Cmax of MK-3120 Total Antibodies (TAb)
5. Serum Ctrough of MK-3120 TAb
6. Plasma Cmax of MK-3120 Free Payload
7. Plasma Ctrough of MK-3120 Free Payload
8. Serum Cmax of Enfortumab Vedotin (EV) ADC
9. Serum Ctrough of EV ADC
10. Serum Cmax of EV TAb
11. Serum Ctrough of EV TAb
12. Plasma Cmax of EV Free Payload
13. Plasma Ctrough of EV Free Payload

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Chethan Ramamurthy

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Chethan Ramamurthy

Third parties 9

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 16 files

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

Application history

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