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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05845814

Registration number

NCT05845814

Ethics application status

Date submitted

26/04/2023

Date registered

6/05/2023

Date last updated

20/02/2024

Titles & IDs

Public title

A Study of Efficacy and Safety of Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04)

Scientific title

A Phase 1/2 Randomized, Umbrella Study to Evaluate the Safety and Efficacy of Pembrolizumab Plus Enfortumab Vedotin (EV) in Combination With Investigational Agents Versus Pembrolizumab Plus EV, as First-Line Treatment for Participants With Advanced Urothelial Carcinoma (KEYMAKER-U04): Substudy 04B

Secondary ID [1]

MK-3475-04B

Secondary ID [2]

3475-04B

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Metastatic Urothelial Carcinoma

Urothelial Neoplasms

Condition category

Condition code

Cancer

Non melanoma skin cancer

Cancer

Kidney

Cancer

Bladder - transitional cell cancer

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Other interventions - Coformulated favezelimab/pembrolizumab
Other interventions - Coformulated vibostolimab/pembrolizumab
Combination Product - EV
Other interventions - Pembrolizumab

Experimental: Arm A: Coformulated favezelimab/pembrolizumab plus EV - Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) as an intravenous (IV) infusion on Day 1 of every 3-week cycle for up to ~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision.

Experimental: Arm B: Coformulated vibostolimab/pembrolizumab plus EV - Participants will receive coformulated vibostolimab/pembrolizumab (200 mg/200 mg) as an IV infusion on Day 1 of every 3-week cycle, for up to ~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision.

Active Comparator: Arm C: Pembrolizumab plus EV - Participants will receive 200 mg pembrolizumab as an IV infusion on Day 1 of every 3-week cycle for up to ~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle, until disease progression, intolerable toxicity, or investigator decision.

Other interventions: Coformulated favezelimab/pembrolizumab
Coformulated favezelimab/pembrolizumab (800 mg/200 mg) IV infusion

Other interventions: Coformulated vibostolimab/pembrolizumab
Coformulated vibostolimab/pembrolizumab (200 mg/200 mg) IV infusion

Combination Product: EV
1.25 mg/kg IV infusion

Other interventions: Pembrolizumab
200 mg IV infusion

Intervention code [1]

Other interventions

Intervention code [2]

Combination Product

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part 1: Objective Response Rate (ORR)

Timepoint [1]

Up to ~4 years

Primary outcome [2]

Part 1: Percentage of Participants experiencing an Adverse Event (AE)

Timepoint [2]

Up to ~4 years

Primary outcome [3]

Part 1: Percentage of Participants who Discontinue study interventions due to an AE

Timepoint [3]

Up to ~4 years

Primary outcome [4]

Part 1: Percentage of Participants with Dose-limiting toxicities (DLT)

Timepoint [4]

Up to 21 days

Primary outcome [5]

Part 2: Progression Free Survival (PFS)

Timepoint [5]

Up to ~4 years

Secondary outcome [1]

Part 1: PFS

Timepoint [1]

Up to ~4 years

Secondary outcome [2]

Part 1: Duration of Response (DOR)

Timepoint [2]

Up to ~4 years

Secondary outcome [3]

Part 2: Overall Survival (OS)

Timepoint [3]

Up to ~4 years

Secondary outcome [4]

Part 2: ORR

Timepoint [4]

Up to ~4 years

Secondary outcome [5]

Part 2: DOR

Timepoint [5]

Up to ~4 years

Secondary outcome [6]

Part 2: Percentage of Participants experiencing an Adverse Event (AE)

Timepoint [6]

Up to ~4 years

Secondary outcome [7]

Part 2: Percentage of Participants who Discontinue study interventions due to an AE

Timepoint [7]

Up to ~4 years

Secondary outcome [8]

Part 2: Percentage of Participants with Dose-limiting toxicities (DLT)

Timepoint [8]

Up to 21 days

Secondary outcome [9]

Part 1: Mean Change from baseline in the global health status/quality of life of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLC-C30) (Items 29 and 30)

Timepoint [9]

Baseline and up to ~4 years

Secondary outcome [10]

Part 1: Mean Change from baseline in the physical functioning scale of the EORTC QLQ-C30

Timepoint [10]

Baseline and up to ~4 years

Secondary outcome [11]

Part 1: Mean Change from Baseline in the European Quality of Life 5 Dimensions, 5-level Questionnaire (EQ-5D-5L) visual analog score (VAS)

Timepoint [11]

Baseline and up to ~4 years

Secondary outcome [12]

Part 2: Mean Change from baseline in the global health status/quality of life of the EORTC QLC-C30 (Items 29 and 30)

Timepoint [12]

Baseline and up to ~4 years

Secondary outcome [13]

Part 2: Mean Change from baseline in the physical functioning scale of the EORTC QLQ-C30

Timepoint [13]

Baseline and up to ~4 years

Secondary outcome [14]

Part 2: Mean Change from Baseline in the EQ-5D-5L visual analog score (VAS)

Timepoint [14]

Baseline and up to ~4 years

Secondary outcome [15]

Part 1: Time-to-Deterioration (TTD) for the global health status/quality of life of the EORTC QLQ-C30 (Items 29 and 30)

Timepoint [15]

Up to ~4 years

Secondary outcome [16]

Part 1: TTD for the physical functioning scale of the EORTC QLQ-C30

Timepoint [16]

Up to ~4 years

Secondary outcome [17]

Part 1: TTD for the EQ-5D-5L VAS

Timepoint [17]

Up to ~4 years

Secondary outcome [18]

Part 2: TTD for the global health status/quality of life of the EORTC QLQ-C30 (Items 29 and 30)

Timepoint [18]

Up to ~4 years

Secondary outcome [19]

Part 2: TTD for the physical functioning scale of the EORTC QLQ-C30

Timepoint [19]

Up to ~4 years

Secondary outcome [20]

Part 2: TTD for the EQ-5D-5L VAS

Timepoint [20]

Up to ~4 years

Eligibility

Key inclusion criteria

- Must have histologically documented, locally advanced/metastatic urothelial carcinoma
(la/mUC).

- Participants with mixed histology are eligible provided the urothelial component
is =50% (and <10% plasmacytoid component)

- Participants whose tumors contain any neuroendocrine component are not eligible
(variant histology to be confirmed locally)

- Must not have received prior systemic therapy for la/mUC. The following therapies in
earlier disease setting (eg, muscle-invasive urothelial carcinoma (MIUC)) are
permitted:

- Participants that received neoadjuvant or adjuvant chemotherapy are permitted.

- Participants who received anti- programmed cell death 1 protein (PD-1) or
programmed cell death ligand 1 (PD-L1) therapy for an earlier disease stage (eg,
NMIBC, MIUC) with progression/recurrence >12 months from completion of therapy
are permitted.

- 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. A newly obtained biopsy is strongly preferred, but not required
if archival tissue is evaluable.

- Any AEs due to previous anticancer therapies must have recovered to =Grade 1 or
baseline. Endocrine-related AEs adequately treated with hormone replacement or with
<Grade 2 neuropathy are eligible.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

- Has a known additional malignancy, except if the participant has undergone potentially
curative therapy with no evidence of that disease recurrence for at least 3 years
since initiation of that therapy.

- Central nervous system (CNS) metastases are permitted on-study if all of the following
are true: a) CNS metastases have been clinically stable for at least 4 weeks prior to
screening and baseline scans show no evidence of new or enlarged metastasis; b) the
participant is on a stable dose of =10 mg/day of prednisone or equivalent for at least
2 weeks (if requiring steroid treatment); c) participant does not have leptomeningeal
disease.

- Has received a live or live-attenuated vaccine within 30 days prior to the first dose
of study intervention.

- Has received an investigational agent or has used an investigational device within 4
weeks prior to study intervention administration.

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
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.

- Has active keratitis or corneal ulcerations. Superficial punctate keratitis is allowed
if the disorder is being adequately treated in the opinion of the investigator.

- Has an active autoimmune disease that has required systemic treatment in past 2 years
except replacement therapy.

- Has a history of uncontrolled diabetes.

- Has a history of (noninfectious) pneumonitis that required steroids or has current
pneumonitis

- Has an active infection (viral, bacterial, or fungal) requiring systemic therapy.

- Has a known history of human immunodeficiency virus (HIV) infection.

- Has hepatitis B or hepatitis C virus infection.

- Has had major surgery within 4 weeks prior to first dose of study intervention.

- Has had an allogenic tissue/solid organ transplant

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 1/Phase 2

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Active, not recruiting

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

23/06/2023

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

31/05/2027

Actual

Sample size

Target

390

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD,VIC

Recruitment hospital [1]

Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si - Brisbane

Recruitment hospital [2]

Austin Health-Cancer Clinical Trials Centre ( Site 3950) - Heidelberg

Recruitment postcode(s) [1]

4029 - Brisbane

Recruitment postcode(s) [2]

3084 - Heidelberg

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

California

Country [2]

United States of America

State/province [2]

Colorado

Country [3]

United States of America

State/province [3]

Georgia

Country [4]

United States of America

State/province [4]

Indiana

Country [5]

United States of America

State/province [5]

Missouri

Country [6]

United States of America

State/province [6]

New York

Country [7]

United States of America

State/province [7]

Ohio

Country [8]

United States of America

State/province [8]

Pennsylvania

Country [9]

United States of America

State/province [9]

Utah

Country [10]

Canada

State/province [10]

Ontario

Country [11]

Chile

State/province [11]

Region M. De Santiago

Country [12]

Chile

State/province [12]

Valparaiso

Country [13]

Chile

State/province [13]

Antofagasta

Country [14]

France

State/province [14]

Aquitaine

Country [15]

France

State/province [15]

Cote-d Or

Country [16]

France

State/province [16]

Haute-Garonne

Country [17]

France

State/province [17]

Ile-de-France

Country [18]

France

State/province [18]

Rhone

Country [19]

Israel

State/province [19]

Haifa

Country [20]

Israel

State/province [20]

Petah Tikva

Country [21]

Israel

State/province [21]

Ramat Gan

Country [22]

Italy

State/province [22]

Lombardia

Country [23]

Italy

State/province [23]

Napoli

Country [24]

Korea, Republic of

State/province [24]

Seoul

Country [25]

Netherlands

State/province [25]

Limburg

Country [26]

Netherlands

State/province [26]

Noord-Holland

Country [27]

Netherlands

State/province [27]

Zuid-Holland

Country [28]

Spain

State/province [28]

Barcelona

Country [29]

Spain

State/province [29]

Madrid

Country [30]

Taiwan

State/province [30]

Kaohsiung

Country [31]

Taiwan

State/province [31]

Tainan

Country [32]

Taiwan

State/province [32]

Taipei

Country [33]

United Kingdom

State/province [33]

London, City Of

Funding & Sponsors

Primary sponsor type

Commercial sector/Industry

Name

Merck Sharp & Dohme LLC

Address

Country

Ethics approval

Ethics application status

Summary

Brief summary

This study is a substudy being conducted under one pembrolizumab umbrella master study
KEYMAKER-U04. The substudy will consist of 2 parts. Part 1 will evaluate the efficacy and
safety of coformulated favezelimab/pembrolizumab plus EV and coformulated
vibostolimab/pembrolizumab plus EV relative to pembrolizumab plus EV. There will be no
comparison of coformulated favezelimab/pembrolizumab plus EV versus coformulated
vibostolimab/pembrolizumab plus EV. If ORR and/or DRR are substantially better on
coformulated favezelimab/pembrolizumab plus EV and/or coformulated vibostolimab/pembrolizumab
plus EV compared with pembrolizumab plus EV, after evaluation of the totality of data, the
sponsor might consider Part 2 (expansion) to further characterize the efficacy and safety of
the treatment arms under study.

Trial website

https://clinicaltrials.gov/ct2/show/NCT05845814

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Medical Director

Address

Merck Sharp & Dohme LLC

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05845814