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Brief Title: Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04)

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

INTRODUCTION

  • Org Study ID: 3475-04B
  • Secondary ID: N/A
  • NCT ID: NCT05845814
  • Sponsor: Merck Sharp & Dohme LLC

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.

DETAILED DESCRIPTION

The master study for this substudy is MK-3475-U04/KEYMAKER-U04. The master study will not be screening any participants and will not be registered.

  • Overall Status
    Recruiting
  • Start Date
    June 23, 2023
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Part 1: Objective Response Rate (ORR)

Primary Outcome 1 - Timeframe: Up to ~4 years

Primary Outcome 2 - Measure: Part 1: Percentage of Participants experiencing an Adverse Event (AE)

Primary Outcome 2 - Timeframe: Up to ~4 years

Primary Outcome 3 - Measure: Part 1: Percentage of Participants who Discontinue study interventions due to an AE

Primary Outcome 3 - Timeframe: Up to ~4 years

Primary Outcome 4 - Measure: Part 1: Percentage of Participants with Dose-limiting toxicities (DLT)

Primary Outcome 4 - Timeframe: Up to 21 days

Primary Outcome 5 - Measure: Part 2: Progression Free Survival (PFS)

Primary Outcome 5 - Timeframe: Up to ~4 years

CONDITION

  • Metastatic Urothelial Carcinoma
  • Urothelial Neoplasms

ELIGIBILITY

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 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Medical Director

Role: Study Director

Affiliation: Merck Sharp & Dohme LLC

Overall Contact

Name: Medical Director

Phone: 1-888-577-8839

Email: Trialsites@merck.com

LOCATION

Facility Status Contact
Facility: Cleveland Clinic-Taussig Cancer Center ( Site 3036)
Cleveland, Ohio 44195
United States
Status: Recruiting Contact: Contact
Study Coordinator
216-296-5457

Facility: Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si
Brisbane, Queensland 4029
Australia
Status: Recruiting Contact: Contact
Study Coordinator
0403709251

Facility: Austin Health-Cancer Clinical Trials Centre ( Site 3950)
Heidelberg, Victoria 3084
Australia
Status: Recruiting Contact: Contact
Study Coordinator
610420381848

Facility: FALP-UIDO ( Site 3151)
Santiago, Region M. De Santiago 7500921
Chile
Status: Recruiting Contact: Contact
Study Coordinator
56224457254

Facility: Bradfordhill-Clinical Area ( Site 3155)
Santiago, Region M. De Santiago 8420383
Chile
Status: Recruiting Contact: Contact
Study Coordinator
+56998744662

Facility: ONCOCENTRO APYS-ACEREY ( Site 3158)
Viña del Mar, Valparaiso 2520598
Chile
Status: Recruiting Contact: Contact
Study Coordinator
+56992369820

Facility: Centro de Investigación Oncológica del Norte ( Site 3152)
Antofagasta, 1240000
Chile
Status: Recruiting Contact: Contact
Study Coordinator
56994198125

Facility: centre hospitalier lyon sud ( Site 3606)
Pierre-Bénite, Rhone 69310
France
Status: Recruiting Contact: Contact
Study Coordinator
+33 478861771

Facility: Rambam Health Care Campus-Oncology Division ( Site 3501)
Haifa, 3109601
Israel
Status: Recruiting Contact: Contact
Study Coordinator
97247776750

Facility: Rabin Medical Center-Oncology ( Site 3504)
Petah Tikva, 4941492
Israel
Status: Recruiting Contact: Contact
Study Coordinator
+972-39378074

Facility: Sheba Medical Center-ONCOLOGY ( Site 3503)
Ramat Gan, 5265601
Israel
Status: Recruiting Contact: Contact
Study Coordinator
0525505090

Facility: Severance Hospital, Yonsei University Health System-Medical oncology ( Site 3903)
Seoul, 03722
Korea, Republic of
Status: Recruiting Contact: Contact
Study Coordinator
82222288138

Facility: Asan Medical Center-Department of Oncology ( Site 3901)
Seoul, 05505
Korea, Republic of
Status: Recruiting Contact: Contact
Study Coordinator
+82230106095

Facility: Samsung Medical Center ( Site 3902)
Seoul, 06351
Korea, Republic of
Status: Recruiting Contact: Contact
Study Coordinator
82234101767

Facility: Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 3302)
Amsterdam, Noord-Holland 1066 CX
Netherlands
Status: Recruiting Contact: Contact
Study Coordinator
31205122569

Facility: Erasmus Medisch Centrum-Medical Oncology ( Site 3303)
Rotterdam, Zuid-Holland 3015 GD
Netherlands
Status: Recruiting Contact: Contact
Study Coordinator
31107041338

Facility: National Cheng Kung University Hospital-Clinical Trial Center ( Site 3803)
Tainan, 704
Taiwan
Status: Recruiting Contact: Contact
Study Coordinator
+886-6-2353535

Facility: National Taiwan University Hospital-Oncology ( Site 3801)
Taipei, 10002
Taiwan
Status: Recruiting Contact: Contact
Study Coordinator
+886-2-2312-3456