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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced or Metastatic Urothelial Carcinoma
• Intervention / Treatment: Drug: Avelumab; Drug: Sacituzumab Govitecan (SG); Drug: M6223; Drug: NKTR-255; Drug: JB100

• Study Type: Interventional
• Enrollment (Actual): 256
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia
    • Flinders Medical Centre
  • Footscray, Australia
    • Sunshine Hospital - PARENT
  • Kurralta Park, Australia
    • Ashford Cancer Centre Research
  • Liverpool, Australia
    • Liverpool Hospital - PARENT
  • Newcastle, Australia
    • Calvary Mater Newcastle - PARENT
  • Southport, Australia
    • Tasman Oncology Research Ltd - Oncology
  • Sydney, Australia
    • Macquarie University Hospital - PARENT
  • Westmead, Australia
    • The Kinghorn Can Cen
• Belgium
  • Antwerp, Belgium
    • ZNA Middelheim - Middelheim - account 2
  • Brasschaat, Belgium
    • AZ Klina - PARENT
  • Brussels, Belgium
    • Institut Jules Bordet - Medical Oncology
  • Ghent, Belgium
    • Universitair Ziekenhuis Gent - Medical Oncology
  • Kortrijk, Belgium
    • AZ Groeninge - Campus Kennedylaan - account 2
  • Libramont, Belgium
    • Centre Hospitalier de l'Ardenne - PARENT
  • Liège, Belgium
    • CHU de Liège - PARENT
  • Wuerzburg, Belgium
    • Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
• Canada
  • Brampton, Canada
    • William Osler Health System - Brampton Civic Hospital
  • Greenfield Park, Canada
    • CISSS de la Monteregie-Centre - Hospital Charles Le Moyne
  • Montreal, Canada
    • CHUM Centre de Recherche
  • Ottawa, Canada
    • The Ottawa Hospital Cancer Centre
• France
  • Angers, France
    • ICO - Site Paul Papin - service d'oncologie medicale
  • Bordeaux, France
    • Institut Bergonié - Service d'Oncologie Médicale
  • Caen, France
    • Centre François Baclesse - Pathologies Gynecologiques
  • Créteil, France
    • Hôpital Henri Mondor - Service d'Oncologie Médicale
  • Le Mans, France
    • Clinique Victor Hugo - Centre Jean Bernard - Service d'Oncologie Médical
  • Lyon, France
    • Centre Leon Berard - Service d'Oncologie Medicale
  • Marseille, France
    • Hôpital de la Timone - service d'urologie
  • Nîmes, France
    • Hopital Caremeau - Service Hématologie Clinique/Oncologie Médicale
  • Paris, France
    • Hôpital Cochin - Hematologie et Oncologie Médicale
  • Poitiers, France
    • CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale
  • Rennes, France
    • CRLCC Eugene Marquis - Service d'Oncologie médicale
  • Saint-Herblain, France
    • ICO - Site René Gauducheau - Service d'Oncologie medicale
  • Strasbourg, France
    • Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale
  • Strasbourg, France
    • Clinique Sainte-Anne - Service d'Oncologie Médicale
  • Hauts De Seine
    • Suresnes, Hauts De Seine, France, 92151
      • Hôpital Foch - Service d'Oncologie Médicale
• Germany
  • Essen, Germany
    • Universitaetsklinikum Essen - Westdeutsches Tumorzentrum
  • Frankfurt, Germany
    • Universitaetsklinikum Frankfurt Goethe-Universitaet - Urologie und Kinderurologie2
  • Halle, Germany
    • Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
  • Mönchengladbach, Germany
    • Kliniken Maria Hilf GmbH - Klinik fuer Urologie
  • Münster, Germany
    • Universitaetsklinikum Muenster - Klinik und Poliklinik fuer Urologie
  • Tübingen, Germany
    • Universitaetsklinikum Tuebingen - Klinik fuer Urologie
  • North Rhine-Westphalia
    • Muenchen, North Rhine-Westphalia, Germany, 41063
      • Kliniken Maria Hilf GmbH - Klinik fuer Urologie
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 0044384
      • Universitaetsklinikum Halle (Saale) - Universitaetsklinik und Poliklinik fuer Urologie
• Greece
  • Athens, Greece
    • General Hospital of Athens "Alexandra"
  • Athens, Greece
    • University General Hospital "Attikon"
  • Athens, Greece
    • Athens Medical Center
  • Thessaloniki, Greece
    • Euromedica General Clinic of Thessaloniki
• Italy
  • Bologna, Italy
    • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica
  • Florence, Italy
    • Azienda Ospedaliera Universitaria Careggi - S.O.D. di Oncologia Medica
  • Forlì, Italy
    • IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST - Oncologia
  • Milan, Italy
    • Ospedale San Raffaele - U.O. di Oncologia Medica
  • Milan, Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori - S.S. Oncologia Medica Genitourinaria
  • Misterbianco, Italy
    • Humanitas Istituto Clinico Catanese - Oncologia Medica
  • Naples, Italy
    • Istituto Nazionale Tumori Fondazione G. Pascale - Oncologia Medica A
  • Naples, Italy
    • Istituto Nazionale Tumori Regina Elena IRCCS - Urologia
  • Padova, Italy
    • IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1
  • Pisa, Italy
    • Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia
  • Ravenna, Italy
    • Ospedale Santa Maria Delle Croci
  • Rome, Italy
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
  • San Giovanni Rotondo, Italy
    • IRCCS Ospedale Casa Sollievo della Sofferenza - Dipartimento di Oncologia Medica
  • Terni, Italy
    • Azienda Ospedaliera S. Maria Di Terni - S.C. Oncologia Medica
• South Korea
  • Daejeon, South Korea
    • Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
  • Gyeonggi-do, South Korea
    • National Cancer Center
  • Seongnam-si, South Korea
    • Seoul National University Bundang Hospital
  • Seoul, South Korea
    • Asan Medical Center
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Seoul National University Hospital
  • Seoul, South Korea
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea
    • The Catholic University of Korea, Seoul St. Mary's Hospital
• Spain
  • Badajoz, Spain
    • Hospital Infanta Cristina - Unidad de Fase I
  • Barcelona, Spain
    • Hospital del Mar - Servicio de Oncologia
  • Barcelona, Spain
    • Hospital de la Santa Creu i Sant Pau - Dept of Oncology
  • Barcelona, Spain
    • Hospital Clinic de Barcelona - Servicio de Oncologia
  • Barcelona, Spain
    • Hospital Universitario Virgen del Rocio - Oncology Service
  • Córdoba, Spain
    • Hospital Universitario Reina Sofia - Dept of Oncology
  • Elche, Spain
    • Hospital General Universitario de Elche - Servicio de Oncologia
  • Lugo, Spain
    • Hospital Universitario Lucus Augusti - Oncology
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
  • Manresa, Spain
    • ALTHAIA, Xarxa assistencial Universitaria de Manresa - Oncology Dept
• Taiwan
  • Kaohsiung City, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung City, Taiwan
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Tainan, Taiwan
    • Chi Mei Hospital, Liouying
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan
    • Chang Gung Memorial Hospital,Linkou
• United Kingdom
  • Manchester, United Kingdom
    • The Christie Hospital - Dept of Oncology
  • Preston, United Kingdom
    • Royal Preston Hospital - Rosemere Cancer Centre
  • Greater London
    • London, Greater London, United Kingdom, 0024514
      • Barts Hospital - Dept of Medical Oncology
• United States
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • Beacon Cancer Care
  • Kansas
    • Kansas City, Kansas, United States, 66205
      • University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN)
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21287-7049
      • Johns Hopkins University
  • Missouri
    • Kansas City, Missouri, United States, 66204
      • AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company - Kansas City, MO at St. Joseph Medical Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Tacoma, Washington, United States, 98405
      • Multicare Health System Tacoma General Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Avelumab; 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.	Drug: Avelumab; 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.; Other Names: MSB0010718C
Experimental: Avelumab + Sacituzumab Govitecan (SG); 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.	Drug: Avelumab; 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.; Other Names: MSB0010718C; Drug: Sacituzumab Govitecan (SG); Participants received intravenous infusion SG at dose of 10 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.; Other Names: IMMU-132; GS-0132; Trodelvy™
Experimental: Avelumab + M6223; 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.	Drug: Avelumab; 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.; Other Names: MSB0010718C; Drug: M6223; Participants intravenous infusion of M6223 at dose of 1600 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.
Experimental: Group D: Avelumab + NKTR-255; 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.	Drug: Avelumab; 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.; Other Names: MSB0010718C; Drug: NKTR-255; Participants intravenous infusion of NKTR-255 at a dose of 3 mcg/kg of body weight once every 4 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.
Other: JB100 (NCT02603432); 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.	Drug: JB100; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator - Avelumab + Sacituzumab Govitecan Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])	PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions. The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times. PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm. PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.	Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator - Avelumab + M6223 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])	PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions. The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times. PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm. PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.	Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator - Avelumab + NKTR-255 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])	PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions. The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times. PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm. PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.	Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, and AEs of Special Interest (AESIs)	Adverse Event (AE): any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as events with onset date or worsening during the on-treatment period, defined as the time from the first dose of study intervention administration days to the last administration day + 30 days, or the start day of subsequent anticancer therapy - 1 day, whichever occurred first. TEAEs included serious AEs and non- serous AEs. AESIs included Infusion-related reactions (IRRs), Immune-related AEs (irAEs), Thromboembolic events, Cytokine release syndrome, QT interval prolongation.	Up to 32 months and 12 days (Current study) and 61 months and 11 days (JB100 extended control group)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) -Avelumab + Sacituzumab Govitecan Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])	OS: time from date of randomization to death. OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates. PS were used as weights to minimize the impact of confounding factors on the estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with the sum of weights adding up to number of participants in randomized control arm. Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates. OS efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.	Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
Overall Survival (OS) - Avelumab + M6223 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])	OS: time from date of randomization to death. OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates. PS were used as weights to minimize the impact of confounding factors on the estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with the sum of weights adding up to number of participants in randomized control arm. Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates. OS efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.	Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
Overall Survival (OS) - Avelumab + NKTR-255 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])	OS: time from date of randomization to death. OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates. PS were used as weights to minimize the impact of confounding factors on the estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with the sum of weights adding up to number of participants in randomized control arm. Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates. OS efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.	Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator- Avelumab + Sacituzumab Govitecan Versus Avelumab	ORR is defined as percentage of participants who achieved either a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST v1.1 from randomization to first observation of progression disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator - Avelumab + M6223 Versus Avelumab	ORR is defined as percentage of participants who achieved either a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST v1.1 from randomization to first observation of progression disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator - Avelumab + NKTR-255 Versus Avelumab	ORR is defined as percentage of participants who achieved either a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST v1.1 from randomization to first observation of progression disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator - Avelumab + Sacituzumab Govitecan Versus Avelumab	DoR was defined as time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to PD or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Time from first documented objective response to PD or death due to any cause, assessed up to 32 months and 12 days
Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator Avelumab + M6223 Versus Avelumab	DoR was defined as time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to PD or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Time from first documented objective response to PD or death due to any cause, assessed up to 32 months and 12 days
Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator - Avelumab + NKTR-255 Versus Avelumab	DoR was defined as time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to PD or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Time from first documented objective response to PD or death due to any cause, assessed up to 32 months and 12 days
Serum Concentrations of Avelumab in Avelumab Monotherapy	Serum concentrations of Avelumab were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".	C1D1 and C3D29 (pre-dose and end of infusion); C2D15, C6D71, C9D113, C12D155, C18D239, C24D323, C30D407, C36D491, C42D575, C48D659, and C54D743 (pre-dose) (each cycle is of 2 weeks)
Serum Concentrations of Avelumab- Avelumab + Sacituzumab Govitecan (SG)	Serum concentrations of Avelumab in investigational arm (Avelumab + Sacituzumab Govitecan (SG) were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".	C1D1 and C2D29 (pre-dose and end of infusion); C1D15, C3D43, C5D85, C7D127, C9D169, C13D253, C17D337, C21D421, C25D505, C29D589, C33D673, and C37D757 (pre-dose) (each cycle is of 4 weeks)
Serum Concentrations of Avelumab- Avelumab + M6623	Serum concentrations of Avelumab in investigational arm (Avelumab + M6623) were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day"	C1D1, C2D15 and C3D29 (pre-dose and end of infusion); C1D2, C2D16 (24 hour) C1D8, C2D22 (168 hours); C6D71, C9D113, C12D155, C18D239, C24D323, C30D407, C36D491, C42D575, C48D659 and C54D743 (Pre-dose) (each cycle is of 2 weeks)
Serum Concentrations of Avelumab- Avelumab + NKTR-255	Serum concentrations of Avelumab in investigational arm (Avelumab + NKTR-255) were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".	C1D1, C2D29, C3D57 and C5D113 (pre-dose and end of infusion); C1D2, C2D30 (24 hour) C1D8, C2D36 (168 hours); C7D169, C10D253, C13D337, C16D421, C19D505, C22D589, C25D673 and C28D757(Pre-dose) (each cycle is of 4 weeks)
Serum Concentrations of Total Antibody of Sacituzumab Govitecan (SG)	Serum concentrations of SG were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".	C1D1 and C2D22 (Pre-dose and end of infusion); C1D8, C2D29, C3D43, C5D85, C5D92, C7D127, C7D134, C9D169, C9D176, C13D253, C17D337, C21D421, C21D428, C25D505, C29D589 and C33D673 (Pre-dose) (each cycle is of 4 weeks)
Serum Concentrations of M6223	Serum concentrations of M6223 were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".	C1D1, C2D15 and C3D29 (pre-dose and end of infusion); C1D2, C2D16 (24 hour) C1D8, C2D22 (168 hours); C6D71, C9D113, C12D155, C18D239, C24D323, C30D407, C36D491, C42D575, C48D659 and C54D743 (Pre-dose) (each cycle is of 2 weeks)
Serum Concentration of NKTR-255	Serum concentrations of NKTR-255 were measured. "C" in the timeframe below refers to "Cycle" and D refers to "Day".	C1D1, C2D29, C3D57 and C5D113 (pre-dose and end of infusion); C1D2, C2D30 (24 hour) C1D8, C2D36 (168 hours); C7D169, C10D253, C13D337, C16D421, C19D505, C22D589, C25D673 and C28D757(Pre-dose) (each cycle is of 4 weeks)
Number of Participants With Positive Anti-Drug Antibody (ADA) of Avelumab and Combination Drugs	Number of participants with positive ADA of Avelumab and combination drugs (Sacituzumab Govitecan [SG], M6223 and NKTR-255) were reported.	Up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
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 at Week 13 - Avelumab + SG Versus Avelumab	The NCCN FACT FBlSI-18 is designed to be a stand-alone instrument to measure symptoms and quality of life in participants with urothelial carcinoma and was created using inputs from participants and oncologists. The disease-related symptoms - physical (DRS-P) subscale uses a subset of physical symptoms which are specific to urothelial carcinoma, i.e., pain, weight loss, urination, weakness, dizziness, meeting family needs, appetite, erection in males, and sleep. Each question offers 5 answers: not at all (0), a little bit (1), somewhat (2), quite a bit (3), very much (4). The overall summary range is 0-36. The scores of negatively stated items (e.g., pain) are reversed and added together with the positively stated scores. The sum of these item scores are multiplied by the number of items in the subscale, i.e., by 9, and divided by the number of items answered. In general, higher scores are better than lower scores.	Baseline, Week 13
Change From Baseline in NCCN FACT FBlSI-18 DRS-P Scores at Week 13 - Avelumab + M6223 Versus Avelumab	The NCCN FACT FBlSI-18 is designed to be a stand-alone instrument to measure symptoms and quality of life in participants with urothelial carcinoma and was created using inputs from participants and oncologists. The disease-related symptoms - physical (DRS-P) subscale uses a subset of physical symptoms which are specific to urothelial carcinoma, i.e., pain, weight loss, urination, weakness, dizziness, meeting family needs, appetite, erection in males, and sleep. Each question offers 5 answers: not at all (0), a little bit (1), somewhat (2), quite a bit (3), very much (4). The overall summary range is 0-36. The scores of negatively stated items (e.g., pain) are reversed and added together with the positively stated scores. The sum of these item scores are multiplied by the number of items in the subscale, i.e., by 9, and divided by the number of items answered. In general, higher scores are better than lower scores.	Baseline, Week 13
Change From NCCN FACT FBlSI-18 DRS-P Scores at Week 13 -Avelumab + NKTR-255 Versus Avelumab	The NCCN FACT FBlSI-18 is designed to be a stand-alone instrument to measure symptoms and quality of life in participants with urothelial carcinoma and was created using inputs from participants and oncologists. The disease-related symptoms - physical (DRS-P) subscale uses a subset of physical symptoms which are specific to urothelial carcinoma, i.e., pain, weight loss, urination, weakness, dizziness, meeting family needs, appetite, erection in males, and sleep. Each question offers 5 answers: not at all (0), a little bit (1), somewhat (2), quite a bit (3), very much (4). The overall summary range is 0-36. The scores of negatively stated items (e.g., pain) are reversed and added together with the positively stated scores. The sum of these item scores are multiplied by the number of items in the subscale, i.e., by 9, and divided by the number of items answered. In general, higher scores are better than lower scores.	Baseline, Week 13

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• Naing A, McKean M, Tolcher A, Victor A, Hu P, Gao W, Nogueira Filho MAF, Kitzing T, Gleicher S, Holland D, Richter E, Tadjalli-Mehr K, Siu LL. TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa in patients with advanced solid tumors: a first-in-human, phase 1, dose-escalation trial. J Immunother Cancer. 2025 Feb 10;13(2):e010584. doi: 10.1136/jitc-2024-010584.
• Hoffman-Censits J, Grivas P, Powles T, Hawley J, Tyroller K, Seeberger S, Guenther S, Jacob N, Mehr KT, Hahn NM. The JAVELIN Bladder Medley trial: avelumab-based combinations as first-line maintenance in advanced urothelial carcinoma. Future Oncol. 2024 Feb;20(4):179-190. doi: 10.2217/fon-2023-0492. Epub 2023 Sep 6.

Helpful Links

• US Medical Information website, Medical Resources
• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2022
• Primary Completion (Actual): June 20, 2025
• Study Completion (Estimated): January 22, 2027

Study Registration Dates

• First Submitted: April 5, 2022
• First Submitted That Met QC Criteria: April 13, 2022
• First Posted (Actual): April 14, 2022

Study Record Updates

• Last Update Posted (Actual): September 1, 2026
• Last Update Submitted That Met QC Criteria: August 10, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Bladder cancer; Avelumab; PD-L1; Avelumab in combination; NKTR-255 (IL-15 agonist); M6223 (anti-TIGIT antibody); Sacituzumab govitecan (Trop-2 antibody drug conjugate)
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; avelumab; sacituzumab govitecan; NKTR-255
• Other Study ID Numbers: MS100070_0119; 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation); 2021-003669-36 (EudraCT Number); 2023-510139-12-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD supporting publicly available results will be evaluated for sharing.

IPD Sharing Time Frame

IPD from completed trials will be publicly available within 6 months after all of the following events:

• Approval of a product/new indication by major authorities (FDA, EMA, PMDA if requested) with no pending submissions
• Public results via primary manuscript or trial registry disclosure
• Legal authority to share data
• Privacy protections are in place If approval is not sought or development is globally discontinued, data will be publicly available within 18 months after global trial completion. Further information on how to request data can be found on our website bit.ly/IPD21

• IPD Sharing Access Criteria: Qualified researchers may propose access to IPD from sponsored trials via https://vivli.org/members/ourmembers/.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No