Berzosertib Human Mass Balance Study (DDRiver Solid Tumors 208)

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: [14C]M6620
* Drug: M6620
* Drug: Topotecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M6620, [14C]M6620 and Topotecan<br> | Drug: [14C]M6620<br>* 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.<br>Drug: M6620<br>* 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.<br>* Other names: MSC2527093A, M6620, VX-970;Drug: Topotecan<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Topotecan, Ataxia telangiectasia mutated and Rad3-related (ATR) protein, ATR inhibitor, M6620, Berzosertib, Mass balance