Tuvusertib (M1774) Human Mass Balance and Absolute Bioavailability Study (DDRIVER Solid Tumors 303)
Phase 1
Recruiting
- Conditions
- Solid Tumor
- Interventions
- Drug: Tuvusertib [14C]Tuvusertib microtracerDrug: Tuvusertib + [14C]Tuvusertib microdose bolus injection
- Registration Number
- NCT06308263
- Lead Sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 12
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Period 1: Mass Balance: Tuvusertib + [14C]Tuvusertib microtracer Tuvusertib [14C]Tuvusertib microtracer - Period 1a: Absolute Bioavailability: Tuvusertib + [14C]Tuvusertib microdose bolus injection Tuvusertib + [14C]Tuvusertib microdose bolus injection - Period 2: Tuvusertib Tuvusertib - Period 1: Mass Balance: Tuvusertib + [14C]Tuvusertib microtracer Tuvusertib - Period 1a: Absolute Bioavailability: Tuvusertib + [14C]Tuvusertib microdose bolus injection Tuvusertib -
- Primary Outcome Measures
Name Time Method 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 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 1: Apparent Terminal Half-Life (t1/2) of TRA in Plasma and Whole Blood 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
Name Time Method 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)
Trial Locations
- Locations (2)
Pharmaceutical Research Associates Magyarország Kutatás - Fejlesztési Kft., Klinikai Farmakológiai Vizsgálóhely
ðŸ‡ðŸ‡ºBudapest, Hungary
Észak Pesti Centrum Kórház-Honvédkórház, Onkológiai Osztály
ðŸ‡ðŸ‡ºBudapest, Hungary