A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants with PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A

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

5 Nov 2025 → ongoing

Decision date (initial)

2024-07-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-506384-34-00

EudraCT number

2020-004544-28

WHO UTN

U1111-1293-7548

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. To assess the safety and tolerability of investigational treatments
2. Arm A: To evaluate objective response rate (ORR) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
3. Arm B: To evaluate the DOR as assessed by investigator per RECIST 1.1

Secondary objectives 2

1. Arm A:To evaluate the duration of response (DOR) as assessed by BICR per RECIST 1.1
2. Arm B: To evaluate the DOR as assessed by investigator per RECIST 1.1

Conditions and MedDRA coding

Locally advanced or metastatic 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 5

1. Histologically or cytologically confirmed diagnosis of locally advanced/unresectable or mUC of the renal pelvis, ureter (upper urinary tract), bladder, or urethra.
2. Arm A: PD-1/L1 refractory locally advanced or mUC as evidenced by: EITHER disease progression while on treatment or after treatment with an anti-PD-1/L1 monoclonal antibody (mAb) for locally advanced/unresectable or mUC administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies; OR disease recurrence while on treatment or after treatment with an anti-PD-1/L1 mAb for muscle-invasive urothelial carcinoma (MIUC) administered as monotherapy.
3. Arm A: Participants must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation.
4. Arm B: PD-1/L1 refractory locally advanced or mUC as evidenced by: EITHER disease progression after treatment with an anti-PD-1/L1 mAb for locally advanced/unresectable or mUC administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies; OR disease recurrence after treatment with an anti-PD-1/L1 mAb for MIUC administered as monotherapy or in combination with other checkpoint therapies >12 months after last dose of treatment with an anti-PD-1/L1 mAb.
5. Arm B: Participants must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion from a metastatic site or from a primary tumor that has become locally advanced and not previously irradiated.

Exclusion criteria 6

1. Known additional nonurothelial malignancy that is progressing or has required active treatment within 3 years prior to study randomization/allocation.
2. Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation.
3. Active infection requiring systemic therapy.
4. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
5. Known history of human immunodeficiency virus (HIV).
6. Known history of hepatitis B or known hepatitis C virus infection.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Percentage of Participants Who Experienced At Least One Adverse Event (AE)
2. Percentage of Participants Who Discontinued Study Treatment Due to an AE
3. Arm A: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)
4. Arm B: ORR as Assessed by Investigator

Secondary endpoints 2

1. Arm A: Duration of Response (DOR) as Assessed by BICR
2. Arm B: DOR as Assessed by Investigator

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

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

David Fogelman

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

David Fogelman

Third parties 9

Locations

4 EU/EEA countries · 8 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 31 files

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

Application history

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