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

Merck KGaA (EMD Serono)

Status and phase: Enrolling; Phase 1

Conditions: Solid Tumor

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06308263

MS201924_0003

2022-502940-10-00 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 12 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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12 participants in 3 patient groups

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

Experimental group

Treatment:

Drug: Tuvusertib

Drug: Tuvusertib [14C]Tuvusertib microtracer

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

Experimental group

Treatment:

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

Drug: Tuvusertib

Period 2: Tuvusertib

Experimental group

Treatment:

Drug: Tuvusertib