Tuvusertib (M1774) Human Mass Balance and Absolute Bioavailability Study (DDRIVER Solid Tumors 303)

Phase 1 Study to Evaluate the Mass Balance, Pharmacokinetics, Metabolism, Excretion and Absolute Bioavailability of Tuvusertib (M1774) Containing Microtracer 14C Tuvusertib in Participants With Advanced Solid Tumors (DDRIVER Solid Tumors 303)

This is a single sequence 2-period open label study in participants with advanced solid tumors. The purpose of Period 1 of this study is to assess the mass balance to determine drug-related entities present in circulation and excreta and provide a comprehensive understanding of biotransformation pathways and clearance mechanisms in participants with advanced solid tumors. The purpose of Period 1a is to assess the extent of ABA of tuvusertib and the mass balance, PK, metabolism, and elimination of 14C-tuvusertib after iv dosing in participants with advanced solid tumors. After either Period 1 or Period 1a; participants may enter an optional extension phase (Period 2) where participants will receive tuvusertib until disease progression or other criteria for study intervention discontinuation are met.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Tuvusertib [14C]Tuvusertib microtracer; Drug: Tuvusertib; Drug: Tuvusertib + [14C]Tuvusertib microdose bolus injection

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary
    • Pharmaceutical Research Associates Magyarország Kutatás - Fejlesztési Kft., Klinikai Farmakológiai Vizsgálóhely

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Are histologically proven advanced solid tumors that are considered appropriate for treatment in Period 2 of this study, for which no effective standard therapy exists, or standard therapy has failed or cannot be tolerated
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) less than or equal to 1 (<=) 1
• Have evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at Screening
• Are capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Uncontrolled or poorly controlled arterial hypertension, symptomatic congestive heart failure (New York Heart Association Classification more than equal to (>=) Class III), uncontrolled cardiac arrhythmia, calculated Corrected QT interval (QTc) average using the QT Interval Corrected Using Fridericia's Formula (QTcF) more than (>) 480 msec; unstable angina pectoris, myocardial infarction, or a coronary revascularization procedure, cerebral vascular accident, transient ischemic attack, or any other significant vascular disease within 180 days of study intervention start
• Presence of toxicities due to prior anticancer therapies (e.g. radiotherapy, chemotherapy, immunotherapies, Et cetera (etc.)) that do not recover to (<=) Grade 1 with the exception of toxicities that do not pose a safety risk to the participant in the judgment of the Investigator (e.g. ongoing Grade 2 alopecia)
• Treatment with live or live attenuated vaccine within 30 days of dosing (non-replicating vector vaccines are permitted)
• Participation in a study involving administration of 14C-labeled compound(s) within last 6 months prior to start of study intervention
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1: Mass Balance: Tuvusertib + [14C]Tuvusertib microtracer	Drug: Tuvusertib [14C]Tuvusertib microtracer; Participants will receive single oral dose of Tuvusertib containing a [14C] Tuvusertib microtracer solution on Day 1 of period 1 under fasted conditions.; Other Names: M1774; Drug: Tuvusertib; Participants will also receive a single oral dose of Tuvusertib on Day 1 of Period 1 or Period 1a, and daily single oral dose of Tuvusertib for 2 weeks in 21 days cycle of Period 2.; Other Names: M1774
Experimental: Period 1a: Absolute Bioavailability: Tuvusertib + [14C]Tuvusertib microdose bolus injection	Drug: Tuvusertib; Participants will also receive a single oral dose of Tuvusertib on Day 1 of Period 1 or Period 1a, and daily single oral dose of Tuvusertib for 2 weeks in 21 days cycle of Period 2.; Other Names: M1774; Drug: Tuvusertib + [14C]Tuvusertib microdose bolus injection; In Period 1a, participants will receive on Day 1 of Period 1 a single oral dose of tuvusertib and an intravenous (IV) (14C) tuvusertib microdose as bolus injection.; Other Names: M1774
Experimental: Period 2: Tuvusertib	Drug: Tuvusertib; Participants will also receive a single oral dose of Tuvusertib on Day 1 of Period 1 or Period 1a, and daily single oral dose of Tuvusertib for 2 weeks in 21 days cycle of Period 2.; Other Names: M1774

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Period 1: Percent Urinary Recovery (feurine) Of Total Radioactivity (TRA) Over the Entire Period Of Collection	Pre-dose up to 312-336 hours post dose
Period 1: Percent Fecal Recovery (fefeces) Of TRA Over the Entire Period Of Collection	Pre-dose up to 312-336 hours post-dose
Period 1: Percent Total Recovery in Urine and Feces (fetotal) Of TRA Over the Entire Period of Collection	Pre-dose up to 312-336 hours post-dose
Period 1: Maximum Observed Concentration (Cmax) of TRA in Plasma and Whole Blood	Pre-dose up to 336 hours post-dose
Period 1: Time to Reach Maximum Concentration (tmax) of TRA in Plasma and Whole blood	Pre-dose up to 336 hours post-dose
Period 1: Area Under Concentration-Time Curve from Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) of TRA in Plasma and Whole Blood	Pre-dose up to 336 hours post-dose
Period 1: Area Under the Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of TRA in Plasma and Whole Blood	Pre-dose up to 336 hours post-dose
Period 1: Apparent Terminal Half-Life (t1/2) of TRA in Plasma and Whole Blood	Pre-dose up to 336 hours post-dose
Period 1 and 1a: Maximum Observed Plasma Concentration (Cmax) Of Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1 and 1a: Time to Reach Maximum Plasma Concentration (Tmax) Of Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1 and 1a: Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) Of Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1 and 1a: Area Under the Plasma Concentration-Time Curve (AUC) from Time Zero Extrapolated to Infinity (AUC0-inf) Of Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1 and 1a: Apparent Terminal Half-Life (t1/2) Of Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1 and 1a: Apparent Total Body Clearance (CL/F) Of Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1 and 1a: Apparent Volume of Distribution (Vz/F) Of Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1a: Ratio of Dose Normalized AUC0-infinity of Tuvusertib and 14C Tuvusertib in Plasma	Pre-dose up to 336 hours post-dose
Period 1a: Initial Concentration (C0) at Time Zero After Bolus Intervention Administration of 14[C] Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1a: Maximum Observed Concentration (Cmax) at Intravenous Administration of 14 [C] Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1a: Total Body Clearance (CL) Following at Intravenous Administration of 14[C] Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1a: Volume of Distribution (Vz) during the terminal phase following intravenous administration of 14[C] Tuvusertib	Pre-dose upto 336 hours post-dose
Period 1a: Volume of Distribution at Steady State (Vss) Following at Intravenous Administration of 14[C] Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1a: Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) at Intravenous Administration of 14[C] Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1a: Area Under the Plasma Concentration-Time Curve (AUC) from Time Zero Extrapolated to Infinity (AUC0-inf) at Intravenous Administration of 14[C] Tuvusertib	Pre-dose up to 336 hours post-dose
Period 1a: Apparent Terminal Half-Life (t1/2) at Intravenous Administration of 14[C] Tuvusertib	Pre-dose up to 336 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Period 1,1a,2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Treatment-Related AEs, Abnormal Laboratory Parameters, abnormal Vital Signs and abnormal 12-Lead Electrocardiogram (ECG) Findings	Baseline up to safety follow up (assessed up to approximately 21 months)

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2024
• Primary Completion (Actual): April 14, 2026
• Study Completion (Actual): April 14, 2026

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: ADME; Ataxia telangiectasia mutated and Rad3-related (ATR) inhibitor; Tuvusertib (M1774)
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hereditary Sensory and Autonomic Neuropathies
• Other Study ID Numbers: MS201924_0003; 2022-502940-10-00 (Other Identifier: EU trial number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No