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

NCT06424717 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: MS202611_00012024-511203-42-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Urothelial Carcinoma

Keywords

M1774; locally advanced and unresectable or metastatic urothelial carcinoma; bladder cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator

  Up to 18 months

• Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator

  Up to 18 months

• Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator

  Up 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 TEAEs

  Up to 18 months

Study Arms (1)

Avelumab with tuvusertib

EXPERIMENTAL

Drug: Avelumab; Drug: Tuvusertib

Interventions

Avelumab DRUG

Participants will be administered Avelumab intravenously (IV).

Also known as: MSB0010718C

Avelumab with tuvusertib

Tuvusertib DRUG

Participants will be administered Tuvusertib orally.

Also known as: M1774

Avelumab with tuvusertib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Related Links

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

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

avelumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Medical Responsible

  EMD Serono Research & Development Institute, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 22, 2024
• Study Start: August 16, 2024
• Primary Completion: January 12, 2026
• Study Completion: January 27, 2026
• Last Updated: September 27, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.