Phase 1 N=6 Treatment

Berzosertib Human Mass Balance Study (DDRiver Solid Tumors 208)

Advanced Solid Tumor

Bottom Line

View on ClinicalTrials.gov: NCT05246111 ↗

Enrolled (actual)

Serious AEs

35.3%

Results posted

Nov 2024

Primary outcome: Primary: Period 1: Percent Urinary Recovery (Feurine) of Total Radioactivity — 15.8 percentage of administered dose (%)

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: [14C]Berzosertib (Drug); Berzosertib (Drug); Topotecan (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Primary completion: Jun 2023

Outcome Measures

Outcome	Result	p-value
PRIMARY Period 1: Percent Urinary Recovery (Feurine) of Total Radioactivity	15.8	—
PRIMARY Period 1: Percent Fecal Recovery (Fefeces) of Total Radioactivity	73.7	—
PRIMARY Period 1: Percent Total Recovery in Urine and Feces (Fetotal) of Total Radioactivity	89.5	—
PRIMARY Period 1: Maximum Observed Plasma Concentration (Cmax) of Berzosertib	1870	—
PRIMARY Period 1: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Berzosertib	8620	—
PRIMARY Period 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Berzosertib	8650	—
PRIMARY Period 1: Terminal Elimination Half-Life (T1/2) of Berzosertib	19.6	—
PRIMARY Period 1: Total Body Clearance (CL) of Berzosertib From Plasma	47.7	—
PRIMARY Period 1: Apparent Volume of Distribution During the Terminal Phase (Vz) of Berzosertib	1340	—
PRIMARY Period 1: Apparent Volume of Distribution at Steady State (Vss) of Berzosertib	930	—
PRIMARY Period 1: Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity	2410	—
PRIMARY Period 1: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Total Radioactivity	38300	—
PRIMARY Period 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Radioactivity	39400	—
PRIMARY Period 1: Terminal Elimination Half-Life (T1/2) of Total Radioactivity	64.3	—
PRIMARY Period 1: Maximum Observed Blood Concentration (Cmax) of Total Radioactivity	2920	—
PRIMARY Period 1: Area Under the Blood Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Total Radioactivity	33100	—
PRIMARY Period 1: Area Under the Blood Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Radioactivity	33900	—
PRIMARY Period 1: Terminal Elimination Half-Life (T1/2) of Total Radioactivity in Blood	30.6	—
PRIMARY Period 1: Cumulative Amount of Berzosertib Dose Excreted in Urine (Aeurine)	41.1	—
PRIMARY Period 1: Percentage of Berzosertib Dose Excreted in Urine (Feurine)	9.84	—
PRIMARY Period 1: Renal Clearance (CLr) of Berzosertib	7.84	—
SECONDARY Period 1 and Period 2: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs	0; 0	—
SECONDARY Period 1 and Period 2: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Measurements	0; 0	—
SECONDARY Period 1 and Period 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs	6; 5; 4; 5	—

Summary

The study was conducted in two periods, Period 1 (mass balance) and Period 2 (extension). The purpose of Period 1 of this study was 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 was to assess safety and efficacy of berzosertib in combination with topotecan.

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05246111). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.