Brief Title: Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator

Primary Outcome 1 - Timeframe: Time from randomization of study drug until first documentation of progressive disease (PD) or death, assessed approximately up to 51 months

Primary Outcome 2 - Measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, and AEs of Special Interest (AESIs) as per Qualitative Toxicity Scale [National Cancer Institute-Common Terminology Criteria for Adverse Events 5.0]

Primary Outcome 2 - Timeframe: From Randomization up to the last safety follow-up visit at approximately up to 51 months

CONDITION

• Locally Advanced or Metastatic Urothelial Carcinoma

ELIGIBILITY

Inclusion Criteria:
Participants with histologically confirmed, unresectable locally advanced or metastatic urothelial carcinoma. Both transitional cell and mixed transitional/non- transitional cell histologies are allowed, but transitional cell carcinoma must be the predominant histology

- Participants has documented Stage IIIA/IIIB with N1-N3, or Stage IV disease (per American Joint Committee on Cancer/International Union for Cancer Control Tumor Node Metastasis system, 8th edition) at the start of first line chemotherapy.

- The last dose of first line chemotherapy must have been received no less than 4 weeks, and no more than 10 weeks, prior to randomization in the present study

- Estimated life expectancy of at least 3 months

- Participants without progressive disease as per RECIST v1.1 guidelines following completion of 4 to 6 cycles of 1L chemotherapy. Eligibility based on this criterion will be determined by Investigator review of pre chemotherapy and post chemotherapy radiological assessments (CT/MRI scans).

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

- Adequate hematological, hepatic, and renal function as defined in the protocol

- Other protocol defined inclusion criteria could apply
Exclusion Criteria:
Participants with prior immunotherapy with Interleukin-2 (IL-2), IL-15, interferon alfa (IFN-α), or an anti programmed death receptor-1 (PD-1), anti programmed death-ligand 1 (PD-L1), anti PD-L2, anti CD137, or cytotoxic T cell lymphocyte-4 (CTLA-4) antibody (including ipilimumab), anti TROP2, anti-T-cell-immuno-receptor with Ig and ITM domains (anti-TIGIT) any other antibody or drug specifically targeting T cell costimulation or immune checkpoint pathways, agents targeting Nectin-4, or any of the investigational drugs used in combination with avelumab.

- Participants with active infection 48 hours before randomization requiring systemic therapy

- Participants with known prior or suspected hypersensitivity to study drugs or any component in their formulations

- Participants with prior adjuvant or neoadjuvant systemic therapy within 12 months of randomization

- Participants with vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines) administered >= 2 weeks prior first dose of study treatment. All severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccines approved or authorized by local Health Authorities are allowed

- Other protocol defined exclusion criteria could apply

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Medical Responsible

Role: Study Director

Affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Overall Contact

Name: Medical Responsible

Phone: 888-275-7376, +49 6151 72 5200

Email: eMediUSA@emdserono.com, service@emdgroup.com

LOCATION