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

Urothelial Carcinoma Clinical Trial

Official title:

A Single Arm, Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy, Safety, and Tolerability of Avelumab in Combination With the ATR Inhibitor Tuvusertib in Participants With Advanced Urothelial Carcinoma That Has Progressed on Prior Anti-PD-(L)1 Therapy (JAVELIN DDRiver Bladder)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06424717
• Other study ID #: MS202611_0001
• Secondary ID: 2024-511203-42-0
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 29, 2024
• Est. completion date: January 27, 2026

Study information

• Verified date: April 2024
• Source: EMD Serono
• Contact: US Medical Information
• Phone: 888-275-7376
• Email: eMediUSA[@]emdserono.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 70
• Est. completion date: January 27, 2026
• Est. primary completion date: January 12, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Drug:
• Avelumab
Participants will be administered Avelumab intravenously (IV).
• Tuvusertib
Participants will be administered Tuvusertib orally.

Locations

Country	Name	City	State
Germany	Please Contact the Communication Center	Darmstadt
United States	Please Contact U.S. Medical Information	Rockland	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 Mutations		Up to 18 months
Secondary	Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator		Up to 18 months
Secondary	Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator		Up to 18 months
Secondary	Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator		Up to 18 months
Secondary	Overall Survival (OS)		From the date of randomization until death, assessed up to 1.5 years
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs		Up to 18 months
Secondary	Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator in Subpopulations as Defined by Selected Tumor Biomarkers		Up to 18 months
Secondary	Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator in Subpopulations as Defined by Selected Tumor Biomarkers		Up to 18 months
Secondary	Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator in Subpopulations as Defined by Selected Tumor Biomarkers		Up to 18 months
Secondary	Overall Survival (OS) in Subpopulations as Defined by Selected Tumor Biomarkers		From the date of randomization until death, assessed up to 1.5 years

External Links

•   Trial Awareness and Transparency website