## Protocol Section
### Identification Module
**NCT ID:** NCT06433219

**Brief Title:** Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)

**Official Title:** An Open-label, Multicenter, Randomized Phase 2 Study of the ATR Inhibitor Tuvusertib in Combination With the PARP Inhibitor Niraparib or the ATM Inhibitor Lartesertib in Participants With BRCA Mutant and/or Homologous Recombination deﬁciency (HRD)-Positive Epithelial Ovarian Cancer That Progressed on Prior PARP Inhibitor Therapy (DDRiver EOC 302)

#### Organization Study ID Info
**ID:** MS201924_0002
#### Organization
**Class:** INDUSTRY
**Full Name:** EMD Serono
#### Secondary ID Infos
**Domain:** EU trial number
**ID:** 2024-511202-23-00
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2028-01-25

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-22

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2028-01-10

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-26

**Type:** ESTIMATED

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-05-29
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-22
**Study First Submit QC Date:** 2024-05-22
### 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

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The purpose of this study is to measure the effect and safety of treatment with tuvusertib combined with either niraparib or lartesertib in participants with epithelial ovarian cancer. The participants will previously have progressed while treated with a poly ADP ribose polymerase (PARP) inhibitor. The primary objective of the study is to assess the effect of the treatment in terms of overall response, i.e. whether the tumor disappears, shrinks, remains unchanged, or gets worse.

### Conditions Module

**Conditions:**

- Ovarian Cancer

**Keywords:**

- Ataxia telangiectasia mutated Rad3-related

- Ataxia telangiectasia mutated

- Poly-ADP ribose polymerase inhibitor resistance

- Homologous recombination deficiency

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: Tuvusertib (M1774)

- Drug: Niraparib

**Label:** Tuvusertib with Niraparib

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: Tuvusertib (M1774)

- Drug: Lartesertib (M4076)

**Label:** Tuvusertib with Lartesertib

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Tuvusertib with Lartesertib

- Tuvusertib with Niraparib

**Description:** Tuvusertib will be administered orally

**Name:** Tuvusertib (M1774)

**Other Names:**

- M1774, VXc-400, VRT-1363004, substance code MSC2584415A

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Tuvusertib with Niraparib

**Description:** Niraparib will be administered orally

**Name:** Niraparib

**Other Names:**

- GSK3985771, MK-4827

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Tuvusertib with Lartesertib

**Description:** Lartesertib will be administered orally

**Name:** Lartesertib (M4076)

**Other Names:**

- M4076, substance code MSC2585823A

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

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

**Time Frame:** Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years.

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

**Time Frame:** Time from randomization to final assessment at end of safety follow-up visit, approximately up to 3.5 years.

#### Secondary Outcomes

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

**Time Frame:** Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years.

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

**Time Frame:** Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years.

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Histologically or cytologically confirmed high grade serous or high grade endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer that is recurrent.
* Participants whose tumor carries germline or somatic deleterious or suspected deleterious mutations in the genes BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2), and/or tumors with positive HRD status. The presence of any of these mutations and/or the homologous recombination deficiency (HRD) status will be determined according to routinely used local standard of care tests. Results must be available before screening.
* Radiologically confirmed/documented disease progression while on Poly (ADP-ribose) polymerase (PARP) inhibitors therapy in either first or second-line maintenance setting (only 1 line of PARPi maintenance is allowed with or without bevacizumab). Note: Documentation of disease progression must be within 28 days of last PARPi dose taken. Surgical salvage intervention and/or focal ablative therapies are allowed, (further disease progression after these interventions must be documented), AND Clinically benefited from PARPi maintenance prior to documented progression, as defined by at least 6 months of treatment duration with no progressive disease observed, AND either, Progression on first-line maintenance PARPi: Participants are allowed maximum 1 additional line of platinum-based chemotherapy before study entry. (note: treatment-free interval on platinum rechallenge must be \>6 months, with documented disease progression prior to study entry).

OR Progression on second-line maintenance PARPi: Participants are not allowed any additional systemic anticancer treatments before study entry (i.e. PARPi is the last treatment before study entry)

* Measurable disease per RECIST v1.1, as assessed by Investigator.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 6 months.
* Other Protocol defined inclusion criteria.

Exclusion Criteria:

* Primary platinum-refractory disease defined as disease progression during primary platinum-based chemotherapy or platinum-resistant disease defined as disease progression within 6 months of the last platinum administration in the second-line setting.
* History of additional malignancy within 3 years before the date of enrollment.
* Known brain metastases, unless clinically stable, i.e. without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention, no evidence of new brain metastases, and on a stable or decreasing dose of ≤ 10 mg of prednisone (or equivalent) or without corticosteroids for at least 14 days prior to study intervention administration.
* Active and/or uncontrolled infection.
* History of known hypersensitivity to the active substances or to any excipients (e.g. polysorbate 80) of the study interventions.
* Organ transplantation, including allogenic stem cell transplant.
* Other Protocol defined exclusion criteria.

**Gender Based:** True

**Minimum Age:** 18 Years

**Sex:** FEMALE

**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: D000004701

- Term: Endocrine Gland Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000010049

- Term: Ovarian Diseases

- ID: D000000291

- Term: Adnexal Diseases

- ID: D000005831

- Term: Genital Diseases, Female

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000005833

- Term: Genital Neoplasms, Female

- ID: D000014565

- Term: Urogenital Neoplasms

- ID: D000091662

- Term: Genital Diseases

- ID: D000004700

- Term: Endocrine System Diseases

- ID: D000006058

- Term: Gonadal Disorders

- ID: D000002277

- Term: Carcinoma

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BXS

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

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M12974

- Name: Ovarian Neoplasms

- Relevance: HIGH

- As Found: Ovarian Cancer

- ID: M1704

- Name: Carcinoma, Ovarian Epithelial

- Relevance: HIGH

- As Found: Ovarian Cancer

- ID: M4565

- Name: Ataxia

- Relevance: LOW

- As Found: Unknown

- ID: M5773

- Name: Cerebellar Ataxia

- Relevance: LOW

- As Found: Unknown

- ID: M16456

- Name: Telangiectasis

- Relevance: LOW

- As Found: Unknown

- ID: M4566

- Name: Ataxia Telangiectasia

- Relevance: LOW

- As Found: Unknown

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M7863

- Name: Endocrine Gland Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M12972

- Name: Ovarian Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M3643

- Name: Adnexal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8943

- Name: Genital Diseases, Female

- Relevance: LOW

- As Found: Unknown

- ID: M2876

- Name: Genital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8945

- Name: Genital Neoplasms, Female

- Relevance: LOW

- As Found: Unknown

- ID: M17315

- Name: Urogenital Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9163

- Name: Gonadal Disorders

- Relevance: LOW

- As Found: Unknown

- 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: T4352

- Name: Ovarian Cancer

- Relevance: HIGH

- As Found: Ovarian Cancer

- ID: T4354

- Name: Ovarian Epithelial Cancer

- Relevance: HIGH

- As Found: Ovarian Cancer

- ID: T519

- Name: Ataxia Telangiectasia

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000010051

- Term: Ovarian Neoplasms

- ID: D000077216

- Term: Carcinoma, Ovarian Epithelial

### Intervention Browse Module - Ancestors

- ID: D000067856

- Term: Poly(ADP-ribose) Polymerase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- 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: M289466

- Name: Niraparib

- Relevance: HIGH

- As Found: Thigh

- ID: M205

- Name: Poly(ADP-ribose) Polymerase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000545685

- Term: Niraparib

### Misc Info Module

- Version Holder: 2024-05-31
