## Protocol Section
### Identification Module
**NCT ID:** NCT06421935

**Brief Title:** M9466 as Single Agent or in Combination With Tuvusertib in Advanced Solid Tumors (DDRiver 501)

**Official Title:** An Open Label, Multicenter, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of the PARP1 Inhibitor M9466 as a Single Agent and in Combination With the ATR Inhibitor Tuvusertib in Participants With Advanced Solid Tumors (DDRiver 501)

#### Organization Study ID Info
**ID:** MS202659_0001
#### Organization
**Class:** INDUSTRY
**Full Name:** EMD Serono
#### Secondary ID Infos
**Domain:** EU CTR
**ID:** 2024-513492-41-00
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2026-03-26

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-03-09

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-14
### 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 evaluate the safety, tolerability, pharmacokinetics, pharmacodynamic, and preliminary clinical activity of M9466 as monotherapy or in combination with tuvusertib in participants with advanced solid tumors. Study details include: Study/Treatment Duration: Participants will be treated until disease progression, death, discontinuation, or End of Study. Visit Frequency: Every week in the first 2 cycles, followed by every 3 weeks in the subsequent cycles. An End of Treatment Visit and Safety Follow-up/Discontinuation Visit are scheduled after the treatment period.

### Conditions Module

**Conditions:**

- Advanced Solid Tumor

**Keywords:**

- PARP inhibitor

- castration-resistant prostate cancer

- ovarian cancer

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 70

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: M9466

- Drug: Tuvusertib

**Label:** M9466 plus Tuvusertib

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: M9466

**Label:** M9466 Monotherapy

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- M9466 Monotherapy

- M9466 plus Tuvusertib

**Description:** Participants will be administered M9466 orally.

**Name:** M9466

**Other Names:**

- HRS-1167;

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- M9466 plus Tuvusertib

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

**Name:** Tuvusertib

**Other Names:**

- Substance code MSC2584415A; also known as M1774, VXc-400, or VR 1363004

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Module 1 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs

**Time Frame:** Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)

**Measure:** Module 1 Part A1: Number of Participants with Dose Limiting Toxicity (DLT)-like events

**Time Frame:** Day 1 up to Day 21 of Cycle 1 (each cycle is of 21 days)

**Measure:** Module 2 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466

**Time Frame:** Day 1, Day 8 and Day 15

#### Secondary Outcomes

**Measure:** Module 1 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 and Tuvusertib

**Time Frame:** Day 1, Day 8 and Day 15

**Measure:** Module 1 Part A1: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as Assessed by Investigator

**Time Frame:** Time from first treatment to planned assessment at 12 months

**Measure:** Module 1 Part A1: Effect of M9466 in combination with tuvusertib on QTc interval as determined by Digital ECGs

**Time Frame:** Time from first treatment to planned assessment at 12 months

**Measure:** Module 2 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-Related AEs

**Time Frame:** Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)

**Measure:** Module 2 Part A1: Number of Participants with Abnormalities in Digital Electrocardiogram (ECG) Measures

**Time Frame:** Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)

**Measure:** Module 2 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 and Tuvusertib

**Time Frame:** Day 1, Day 8 and Day 15

**Measure:** Module 2 Part A1: Relative Changes in Pharmacodynamic Markers In Paired Tumor Biopsies

**Time Frame:** Day 1, Day 8 and Day 15

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Module 1 Part A1 and Module 2 Part A1: Locally advanced or metastatic disease that is refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator
* Eastern Cooperative Oncology Group Performance Status less than or equal to (\<=) 1
* Life expectancy of more than 6 months
* Have adequate hematologic function
* Participants who received chemotherapy, extensive radiotherapy, biological therapy (e.g. antibodies) or investigational agents will have a washout period of 4 weeks (6 weeks for nitrosourea, mitomycin-C) or 5 half-lives whichever is shorter, prior to starting study intervention with M9466 (± tuvusertib)
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Persistence of Adverse Events related to any prior treatments that have not recovered to Grade less than 1 by NCI Common Terminology Criteria for Adverse Events- v5.0 unless AEs are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator (e.g. neuropathy or alopecia)
* Participant has a history of malignancy within 5 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertropia, or malignancy that in the opinion of the Investigator, with concurrence of the Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years)
* Participants with known brain metastases, except if clinically controlled, which is defined as individuals with Central Nervous System (CNS) tumors that have been treated, are asymptomatic and who have discontinued steroids (for the treatment of CNS tumors) for more than 28 days
* 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
* Cerebrovascular accident or stroke
* 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

**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 the 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:** NO

### References Module

#### See Also Links

**Label:** Trial Awareness and Transparency website

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

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BXS

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

- Abbrev: All

- Name: All Conditions

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M14335

- Name: Prostatic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M12974

- Name: Ovarian Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M1704

- Name: Carcinoma, Ovarian Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: T4352

- Name: Ovarian Cancer

- Relevance: LOW

- As Found: Unknown

- ID: T4354

- Name: Ovarian Epithelial Cancer

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009369

- Term: Neoplasms

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M205

- Name: Poly(ADP-ribose) Polymerase Inhibitors

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
