A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)

Merck KGaA (EMD Serono)

Status and phase: Active, not recruiting; Phase 2

Conditions: Locally Advanced or Metastatic Urothelial Carcinoma

Treatments: Drug: NKTR-255; Drug: JB100; Drug: M6223; Drug: Sacituzumab Govitecan (SG); Drug: Avelumab

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT05327530

2021-003669-36 (EudraCT Number)

MS100070_0119

2023-510139-12-00 (EU Trial (CTIS) Number)

2023

Details and patient eligibility

About

The purpose of this study is to assess the safety and efficacy of avelumab in combination with other anti-tumor agents as a maintenance treatment in participants with bladder cancer.

Enrollment: 256 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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256 participants in 5 patient groups

Avelumab

Experimental group

Description:

Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Treatment:

Drug: Avelumab

Avelumab + Sacituzumab Govitecan (SG)

Experimental group

Description:

Participants received intravenous infusion of Avelumab at a dose of 800 milligrams (mg) once every 2 weeks in combination with intravenous infusion of SG at dose of 10 milligrams per kilogram (mg/kg) of bodyweight once a week on Day 1 and 8 of each 21-daytreatment cycles until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Treatment:

Drug: Avelumab

Drug: Sacituzumab Govitecan (SG)

Avelumab + M6223

Experimental group

Description:

Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks in combination with intravenous infusion of M6223 at dose of 1600 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Treatment:

Drug: Avelumab

Drug: M6223

Group D: Avelumab + NKTR-255

Experimental group

Description:

Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks in combination with intravenous infusion of NKTR-255 at a dose of 3 micrograms per kilogram (mcg/kg) of body weight once every 4 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Treatment:

Drug: Avelumab

Drug: NKTR-255

JB100 (NCT02603432)

Other group

Description:

As per the Clinical Study Protocol, the control group (avelumab alone) was extended by data from an external control, i.e. the JAVELIN Bladder 100 study (JB100) (NCT02603432). Participants received an intravenous infusion of 10 mg/kg of Avelumab along with best supportive care (BSC), on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered asper the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anticancer therapy.

Treatment:

Drug: JB100