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

May 16, 2024 updated by: EMD Serono Research & Development Institute, Inc.

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)

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Germany
      • Darmstadt, Germany, 64293
        • Please Contact the Communication Center
        • Contact:
          • Please Contact the Communication Center
          • Phone Number: +49 6151 72 5200
          • Email: service@emdgroup.com
  • United States
    • Massachusetts
      • Rockland, Massachusetts, United States, 02370
        • Please Contact U.S. Medical Information
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Avelumab with tuvusertib
Drug: Tuvusertib
Participants will be administered Tuvusertib orally.
Other Names:
  • M1774
Drug: Avelumab
Participants will be administered Avelumab intravenously (IV).
Other Names:
  • MSB0010718C

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: Up to 18 months
Up to 18 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator
Time Frame: Up to 18 months
Up to 18 months
Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator
Time Frame: Up to 18 months
Up to 18 months
Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator
Time Frame: Up to 18 months
Up to 18 months
Overall Survival (OS)
Time Frame: From the date of randomization until death, assessed up to 1.5 years
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
Time Frame: Up to 18 months
Up to 18 months
Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator in Subpopulations as Defined by Selected Tumor Biomarkers
Time Frame: Up to 18 months
Up to 18 months
Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator in Subpopulations as Defined by Selected Tumor Biomarkers
Time Frame: Up to 18 months
Up to 18 months
Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator in Subpopulations as Defined by Selected Tumor Biomarkers
Time Frame: Up to 18 months
Up to 18 months
Overall Survival (OS) in Subpopulations as Defined by Selected Tumor Biomarkers
Time Frame: From the date of randomization until death, assessed up to 1.5 years
From the date of randomization until death, assessed up to 1.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

EMD Serono Research & Development Institute, Inc.

Collaborators

Merck KGaA, Darmstadt, Germany

Investigators

  • Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 29, 2024

Primary Completion (Estimated)

January 12, 2026

Study Completion (Estimated)

January 27, 2026

Study Registration Dates

First Submitted

May 16, 2024

First Submitted That Met QC Criteria

May 16, 2024

First Posted (Actual)

May 22, 2024

Study Record Updates

Last Update Posted (Actual)

May 22, 2024

Last Update Submitted That Met QC Criteria

May 16, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MS202611_0001
  • 2024-511203-42-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

IPD Sharing 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

IPD Sharing 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.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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