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

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05327530

Collaborator

Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics (Other)

252

Enrollment

Locations

Arms

48.3

Anticipated Duration (Months)

31.5

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced or Metastatic Urothelial Carcinoma	Drug: Avelumab Drug: Sacituzumab Govitecan Drug: M6223 Drug: NKTR-255	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

252 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II, Multicenter, Randomized, Open Label, Parallel-Arm, Umbrella Study of Avelumab (MSB0010718C) in Combination With Other AntiTumor Agents as a Maintenance Treatment in Participants With Locally Advanced or Metastatic Urothelial Carcinoma Whose Disease Did Not Progress With First Line Platinum-Containing Chemotherapy (JAVELIN Bladder Medley)

Anticipated Study Start Date :

Aug 15, 2022

Anticipated Primary Completion Date :

Aug 5, 2026

Anticipated Study Completion Date :

Aug 24, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A: Avelumab	Drug: Avelumab Participants will receive avelumab intravenous infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment. Other Names: MSB0010718C
Experimental: Group B: Avelumab + Sacituzumab Govitecan	Drug: Avelumab Participants will receive avelumab intravenous infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment. Other Names: MSB0010718C Drug: Sacituzumab Govitecan Participants will receive sacituzumab govitecan intravenous infusion at dose of 10 milligrams per kilogram (mg/kg) of body weight once a week (Q1W) on Day 1 and 8 of 21-day treatment cycles until unacceptable toxicity, withdraw consent or initiation of a new treatment.
Experimental: Group C: Avelumab + M6223	Drug: Avelumab Participants will receive avelumab intravenous infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment. Other Names: MSB0010718C Drug: M6223 Participants will receive M6223 (anti-T cell-immuno-receptor with Ig and ITM domains [anti-TIGIT]) intravenous infusion at dose of 1600 mg Q2W until unacceptable toxicity, withdraw consent or initiation of a new treatment.
Experimental: Group D: Avelumab + NKTR-255	Drug: Avelumab Participants will receive avelumab intravenous infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment. Other Names: MSB0010718C Drug: NKTR-255 Participants will receive NKTR-255 intravenous infusion at a dose of 3 micrograms per kilogram body weight (mcg/kg) once every 4 weeks (Q4W) until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Outcome Measures

Primary Outcome Measures

Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator [Time from randomization of study drug until first documentation of progressive disease (PD) or death, assessed approximately up to 51 months]
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] [Randomization up to the last safety follow-up visit at approximately up to 51 months]

Secondary Outcome Measures

Overall Survival (OS) [Time from randomization of study drug until death, assessed approximately up to 51 months]
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator [Time from randomization of study drug up to 51 months]
Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator [Time from first documented objective response to PD or death due to any cause, assessed approximately up to 51 months]
Pharmacokinetic Serum Concentration of Avelumab, M6223, Sacituzumab govitecan and NKTR255 [Pre-dose up to safety follow up, assessed approximately up to maximum 51 months]
Number of Participants with Positive Anti-Drug Antibody (ADA) of Avelumab, M6223, Sacituzumab govitecan and NKTR-255 [Baseline up to 51 months]
Change From Baseline in National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (NCCN-FACT) Bladder Symptom Index- 18 (FBlSI-18) Disease Related Symptoms-Physical Subscale (DRS-P) Scores [Baseline, Month 51]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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, any other antibody or drug specifically targeting T cell costimulation or immune checkpoint pathways, 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) and replication-deficient coronavirus vaccines approved or authorized by local Health Authorities
Other protocol defined exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beacon Cancer Care	Coeur d'Alene	Idaho	United States	83814
2	Rush University Medical Center	Chicago	Illinois	United States	60612
3	The Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
4	Washington University	Saint Louis	Missouri	United States	63110
5	Inova Schar Cancer Institute	Falls Church	Virginia	United States	22042
6	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
7	Multicare Health System Tacoma General Hospital	Tacoma	Washington	United States	98405
8	University of Wisconsin Cancer Center	Madison	Wisconsin	United States	53706