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

Advanced Solid Tumor Clinical Trial

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06421935
• Other study ID #: MS202659_0001
• Secondary ID: 2024-513492-41-0
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 1, 2024
• Est. completion date: March 26, 2026

Study information

• Verified date: May 2024
• Source: EMD Serono
• Contact: US Medical Information
• Phone: 888-275-7376
• Email: eMediUSA[@]emdserono.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 70
• Est. completion date: March 26, 2026
• Est. primary completion date: March 9, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• M9466
Participants will be administered M9466 orally.
• Tuvusertib
Participants will be administered Tuvusertib orally.

Locations

Country	Name	City	State
Germany	Please Contact the Communication Center	Darmstadt
United States	Please Contact U.S. Medical Information	Rockland	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Module 1 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs		Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)
Primary	Module 1 Part A1: Number of Participants with Dose Limiting Toxicity (DLT)-like events		Day 1 up to Day 21 of Cycle 1 (each cycle is of 21 days)
Primary	Module 2 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466		Day 1, Day 8 and Day 15
Secondary	Module 1 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 and Tuvusertib		Day 1, Day 8 and Day 15
Secondary	Module 1 Part A1: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as Assessed by Investigator		Time from first treatment to planned assessment at 12 months
Secondary	Module 1 Part A1: Effect of M9466 in combination with tuvusertib on QTc interval as determined by Digital ECGs		Time from first treatment to planned assessment at 12 months
Secondary	Module 2 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-Related AEs		Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)
Secondary	Module 2 Part A1: Number of Participants with Abnormalities in Digital Electrocardiogram (ECG) Measures		Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)
Secondary	Module 2 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 and Tuvusertib		Day 1, Day 8 and Day 15
Secondary	Module 2 Part A1: Relative Changes in Pharmacodynamic Markers In Paired Tumor Biopsies		Day 1, Day 8 and Day 15

External Links

•   Trial Awareness and Transparency website