Berzosertib Human Mass Balance Study (DDRiver Solid Tumors 208)

Phase I Study to Evaluate the Mass Balance, PK, Metabolism and Excretion of Berzosertib (Intravenous) Containing Microtracer [14C]Berzosertib in Participants With Advanced Solid Tumors (DDRiver Solid Tumors 208)

The study will be conducted in two periods, Period 1 (mass balance) and Period 2 (extension). The purpose of Period 1 of this study is to provide a quantitative characterization of the mass balance, rates and routes of elimination, and metabolic pathways after a single intravenous administration of [14C]berzosertib. The purpose of Period 2 is to assess safety and efficacy of berzosertib in combination with topotecan.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: [14C]M6620; Drug: M6620; Drug: Topotecan

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary
    • PRA Magyarország Kft. Fázis I-es Klinikai Farmakológiai Vizsgálóhely
  • Budapest, Hungary
    • Magyar Honvédség Egészségügyi Központ, Podmaniczky utcai telephely, Onkológiai Osztály

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: .

• 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) =< 1
• Evaluable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) at Screening
• Participant has adequate renal, hematological and hepatic function
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Participants with uncontrolled intercurrent illness including, but not limited to, severe active infection including, acute respiratory syndrome coronavirus-2 infection/coronavirus disease 2019 (Covid 19), immune deficiencies, uncontrolled diabetes, uncontrolled arterial hypertension and symptomatic congestive heart failure
• Concurrent participation in another interventional clinical study is not permitted.
• Known hypersensitivity to the study interventions, a similar structural compound, or to one or more excipients used
• Prior or concurrent treatment with a nonpermitted drug/intervention from the first dose of study intervention administration, as defined per protocol.
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: M6620, [14C]M6620 and Topotecan

Drug: [14C]M6620; Participants will receive single intravenous infusion of [14C]M6620 on Day 1 in Period 1 and stay in clinical research unit (CRU) is required until the discharge criteria are met with a maximum confinement period of 15 days.; Drug: M6620; Participants will receive intravenous infusion of M6620 on Day 2 and Day 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation are met.; Other Names: MSC2527093A, M6620, VX-970; Drug: Topotecan; Participants will receive intravenous infusion of topotecan on Day 1 through Day 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation are met.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Period 1: Percent Urinary Recovery (feurine) of Total Radioactivity	Pre-dose until discharge criteria are met, assessed up to 14 days post-dose
Period 1: Percent Fecal Recovery (fefeces) of Total Radioactivity	Pre-dose until discharge criteria are met, assessed up to 14 days post-dose
Period 1: Percent Total Recovery in Urine and Feces (fetotal) of Total Radioactivity	Pre-dose until discharge criteria are met, assessed up to 14 days post-dose
Period 1: Pharmacokinetic (PK) Plasma and Urine Concentration of M6620	Pre-dose until discharge criteria are met, assessed up to 14 days post-dose
Period 1: Pharmacokinetic Plasma and Blood Concentration of Total Radioactivity	Pre-dose until discharge criteria are met, assessed up to 14 days post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Period 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events	Period 1: Baseline up to Day 14; Period 2: From Day 1 of period 2 until disease progression or other criteria for study intervention discontinuation are met (up to a maximum of approximately 14 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

• DDRiver website
• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Actual): June 28, 2023
• Study Completion (Actual): June 28, 2023

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 18, 2022

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 7, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Topotecan; Mass balance; ATR inhibitor; M6620; Berzosertib; Ataxia telangiectasia mutated and Rad3-related (ATR) protein
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Topotecan
• Other Study ID Numbers: MS201923_0008; 2021-002226-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients 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 https://www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

Drug and device information, study documents

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