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Study of Avelumab and Tuvusertib in Participants With Advanced Urothelial Cancer That Has Progressed on Prior Anti-PD-(L)1 Therapy (JAVELIN DDRiver Bladder)

Phase 2
Not yet recruiting
Conditions
Urothelial Carcinoma
Interventions
Registration Number
NCT06424717
Lead Sponsor
EMD Serono Research & Development Institute, Inc.
Brief Summary

The purpose of this study is to assess the antitumor activity of avelumab in combination with tuvusertib in terms of objective response in participants with advanced urothelial carcinoma. Study details include:

Condition/Disease: Participants with urothelial carcinoma (locally advanced and unresectable, or metastatic) that has progressed on prior anti-PD-(L)1 therapy Treatment Duration: Participants will be treated until progressive disease, death, or discontinuation due to e.g. withdrawal of consent or lost to follow-up Visit Frequency: While receiving study intervention, participants will visit the site twice per every 21-day study intervention period. 1 week after end of study intervention, participants will visit the site for an End of Study Intervention Visit, followed by 2 Safety Follow-Up visits at 1 and 3 months after last dose, and thereafter have remote Long-Term Follow-up every 3 months.

Study Duration: The overall study is planned to close after the last participant has been followed up for at least 12 months.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
70
Inclusion Criteria
  • Histologically confirmed, locally advanced, and unresectable or metastatic urothelial carcinoma.
  • No more than 2 lines of therapy for advanced disease. Chemotherapy followed by avelumab (switch maintenance) counts as 1 line of therapy. Additionally, (neo)-adjuvant chemotherapy for Muscle invasive bladder cancer with recurrence or progression within 12 months of last dose, counts as a line of therapy.
  • Measurable disease by RECIST 1.1, as assessed by the Investigator.
  • Eastern Cooperative Oncology Group Performance status 0 to 1.
  • Adequate hematologic function as indicated by:
  • Platelet count more than or equal to 100,000 per microliter
  • Absolute neutrophil count more than or equal to 1,500 per microliter with no growth factor treatment within the last 14 days
  • Hemoglobin more than or equal to 9.0 gram/deciliter with no erythropoietin or red blood cell transfusion within the last 14 days
  • Only one line of an antibody-drug conjugate (ADC) is allowed.
  • Other protocol defined inclusion criteria could apply.
Exclusion Criteria
  • Any condition, including any uncontrolled disease state other than aUC, that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation.
  • Any known additional malignancy that is progressing and/or requires active treatment including adjuvant hormonal therapy.
  • Presence of brain metastases unless clinically stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention and any neurologic symptoms have returned to baseline and sequelae that are a consequence of the treatment of the brain metastases are acceptable), no evidence of new brain metastases, and on a stable or decreasing dose or without steroids for at least 14 days prior to first dose of study intervention. Participants with carcinomatous meningitis are excluded regardless of clinical stability.
  • Serious gastrointestinal bleeding within 3 months, refractory nausea and vomiting, uncontrolled diarrhea, known malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes, other chronic gastrointestinal disease (including exocrine pancreatic insufficiency requiring pancreatic enzyme replacement therapy), and/or other situations that may preclude adequate absorption of oral medications.
  • Other protocol defined exclusion criteria could apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Avelumab with tuvusertibAvelumab-
Avelumab with tuvusertibTuvusertib-
Primary Outcome Measures
NameTimeMethod
Confirmed Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 as Assessed by Investigator in Participants with Selected Tumor Chromatin Modifier MutationsUp to 18 months
Secondary Outcome Measures
NameTimeMethod
Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by InvestigatorUp to 18 months
Duration of Response (DoR) According to RECIST 1.1 as Assessed by the InvestigatorUp to 18 months
Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the InvestigatorUp to 18 months
Overall Survival (OS)From the date of randomization until death, assessed up to 1.5 years
Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEsUp to 18 months
Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator in Subpopulations as Defined by Selected Tumor BiomarkersUp to 18 months
Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator in Subpopulations as Defined by Selected Tumor BiomarkersUp to 18 months
Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator in Subpopulations as Defined by Selected Tumor BiomarkersUp to 18 months
Overall Survival (OS) in Subpopulations as Defined by Selected Tumor BiomarkersFrom the date of randomization until death, assessed up to 1.5 years

Trial Locations

Locations (2)

Please Contact the Communication Center

🇩🇪

Darmstadt, Germany

Please Contact U.S. Medical Information

🇺🇸

Rockland, Massachusetts, United States

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