## Protocol Section
### Identification Module
**NCT ID:** NCT06424717

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

**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)

#### Organization Study ID Info
**ID:** MS202611_0001
#### Organization
**Class:** INDUSTRY
**Full Name:** EMD Serono
#### Secondary ID Infos
**Domain:** EU CT Number
**ID:** 2024-511203-42-00
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2026-01-27

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-01-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-29

**Type:** ESTIMATED

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-16
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Merck KGaA, Darmstadt, Germany

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** EMD Serono Research & Development Institute, Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

### Description Module

**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 Module

**Conditions:**

- Urothelial Carcinoma

**Keywords:**

- M1774

- locally advanced and unresectable or metastatic urothelial carcinoma

- bladder cancer

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 70

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: Avelumab

- Drug: Tuvusertib

**Label:** Avelumab with tuvusertib

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Avelumab with tuvusertib

**Description:** Participants will be administered Avelumab intravenously (IV).

**Name:** Avelumab

**Other Names:**

- MSB0010718C

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Avelumab with tuvusertib

**Description:** Participants will be administered Tuvusertib orally.

**Name:** Tuvusertib

**Other Names:**

- M1774

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** 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

#### Secondary Outcomes

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

**Time Frame:** Up to 18 months

**Measure:** Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator

**Time Frame:** Up to 18 months

**Measure:** Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator

**Time Frame:** Up to 18 months

**Measure:** Overall Survival (OS)

**Time Frame:** From the date of randomization until death, assessed up to 1.5 years

**Measure:** Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs

**Time Frame:** Up to 18 months

**Measure:** 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

**Measure:** 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

**Measure:** 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

**Measure:** 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

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** eMediUSA@emdserono.com

**Name:** US Medical Information

**Phone:** 888-275-7376

**Role:** CONTACT

**Contact 2:**

**Email:** service@emdgroup.com

**Name:** Communication Center

**Phone:** +49 6151 72 5200

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Rockland

**Contacts:**

***Contact 1:***

- **Email:** eMediUSA@emdserono.com

- **Name:** Please Contact U.S. Medical Information

- **Phone:** 888-275-7376

- **Role:** CONTACT

**Country:** United States

**Facility:** Please Contact U.S. Medical Information

**State:** Massachusetts

**Zip:** 02370

**Location 2:**

**City:** Darmstadt

**Contacts:**

***Contact 1:***

- **Email:** service@emdgroup.com

- **Name:** Please Contact the Communication Center

- **Phone:** +49 6151 72 5200

- **Role:** CONTACT

**Country:** Germany

**Facility:** Please Contact the Communication Center

**Zip:** 64293

#### Overall Officials

**Official 1:**

**Affiliation:** EMD Serono Research & Development Institute, Inc.

**Name:** Medical Responsible

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**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.

**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

**Info Types:**

- STUDY_PROTOCOL

- SAP

- CSR

- ANALYTIC_CODE

**IPD Sharing:** YES

**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

**URL:** http://bit.ly/IPD21

### References Module

#### See Also Links

**Label:** Trial Awareness and Transparency website

**URL:** https://clinicaltrials.emdgroup.com/en

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: HIGH

- As Found: Carcinoma

- ID: M5030

- Name: Urinary Bladder Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M5551

- Name: Carcinoma, Transitional Cell

- Relevance: HIGH

- As Found: Urothelial Carcinoma

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: T5693

- Name: Transitional Cell Carcinoma

- Relevance: HIGH

- As Found: Urothelial Carcinoma

### Condition Browse Module - Meshes

- ID: D000002277

- Term: Carcinoma

- ID: D000002295

- Term: Carcinoma, Transitional Cell

### Intervention Browse Module - Ancestors

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000970

- Term: Antineoplastic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M344580

- Name: Avelumab

- Relevance: HIGH

- As Found: Reach

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000609138

- Term: Avelumab

### Misc Info Module

- Version Holder: 2024-05-31
