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

NCT06308263 | Completed Phase 1

• 2 other identifiers: MS201924_00032022-502940-10-00
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumor

Keywords

Ataxia telangiectasia mutated and Rad3-related (ATR) inhibitor; ADME; Tuvusertib (M1774)

Outcome Measures

Primary Outcomes (24)

• 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 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 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 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 Outcomes (1)

• 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)

Study Arms (3)

Period 1: Mass Balance: Tuvusertib + [14C]Tuvusertib microtracer

EXPERIMENTAL

Drug: Tuvusertib [14C]Tuvusertib microtracer; Drug: Tuvusertib

Period 1a: Absolute Bioavailability: Tuvusertib + [14C]Tuvusertib microdose bolus injection

EXPERIMENTAL

Drug: Tuvusertib; Drug: Tuvusertib + [14C]Tuvusertib microdose bolus injection

Period 2: Tuvusertib

EXPERIMENTAL

Drug: Tuvusertib

Interventions

Tuvusertib DRUG

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.

Also known as: M1774

Period 1: Mass Balance: Tuvusertib + [14C]Tuvusertib microtracer; Period 1a: Absolute Bioavailability: Tuvusertib + [14C]Tuvusertib microdose bolus injection; Period 2: Tuvusertib

Tuvusertib [14C]Tuvusertib microtracer DRUG

Participants will receive single oral dose of Tuvusertib containing a \[14C\] Tuvusertib microtracer solution on Day 1 of period 1 under fasted conditions.

Also known as: M1774

Period 1: Mass Balance: Tuvusertib + [14C]Tuvusertib microtracer

Tuvusertib + [14C]Tuvusertib microdose bolus injection DRUG

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.

Also known as: M1774

Period 1a: Absolute Bioavailability: Tuvusertib + [14C]Tuvusertib microdose bolus injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

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

Budapest, Hungary

Location

Related Links

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

MeSH Terms

Conditions

Hereditary Sensory and Autonomic Neuropathies

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2024
• First Posted: March 13, 2024
• Study Start: March 25, 2024
• Primary Completion: April 14, 2026
• Study Completion: April 14, 2026
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)