Trial Outcomes & Findings for Berzosertib Human Mass Balance Study (DDRiver Solid Tumors 208) (NCT NCT05246111)
NCT ID: NCT05246111
Last Updated: 2024-11-22
Results Overview
Feurine, fractions of total radioactivity excreted in urine as percentage of the administered dose between time t1 (= start) and t2 (= end).
COMPLETED
PHASE1
6 participants
Predose, 0-4, 4-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose
2024-11-22
Participant Flow
First Participant Signed Informed Consent: 15-Feb-2022; Last Participant Last Visit: 28-Jun-2023
Participant milestones
| Measure |
[14C]Berzosertib
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 01
STARTED
|
6
|
0
|
|
Period 01
COMPLETED
|
5
|
0
|
|
Period 01
NOT COMPLETED
|
1
|
0
|
|
Period 02
STARTED
|
0
|
5
|
|
Period 02
COMPLETED
|
0
|
5
|
|
Period 02
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
[14C]Berzosertib
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 01
NOT ELIGIBLE IC5
|
1
|
0
|
Baseline Characteristics
Berzosertib Human Mass Balance Study (DDRiver Solid Tumors 208)
Baseline characteristics by cohort
| Measure |
All Participants
n=6 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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. In Period 2, participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|
|
Age, Continuous
|
52 Years
STANDARD_DEVIATION 16.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose, 0-4, 4-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: The Pharmacokinetic (PK) Analysis Set was a subset of the safety analysis set (SAF) included all participants who received at least one dose of Investigational Manufacturing product (IMP), in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Feurine, fractions of total radioactivity excreted in urine as percentage of the administered dose between time t1 (= start) and t2 (= end).
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Percent Urinary Recovery (Feurine) of Total Radioactivity
|
15.8 percentage of administered dose (%)
Standard Deviation 3.2
|
—
|
PRIMARY outcome
Timeframe: Predose, 0-4, 4-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Fefeces, fractions of total radioactivity excreted in feces as percentage of the administered dose between time t1 (= start) and t2 (= end).
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Percent Fecal Recovery (Fefeces) of Total Radioactivity
|
73.7 percentage of administered dose (%)
Standard Deviation 6.56
|
—
|
PRIMARY outcome
Timeframe: Predose, 0-4, 4-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Fetotal, fractions of total radioactivity excreted in urine and feces as percentage of the administered dose between time t1 (= start) and t2 (= end).
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Percent Total Recovery in Urine and Feces (Fetotal) of Total Radioactivity
|
89.5 percentage of administered dose (%)
Standard Deviation 7.04
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Cmax was obtained directly from the plasma concentration versus time curve.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Maximum Observed Plasma Concentration (Cmax) of Berzosertib
|
1870 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 12.7
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
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 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 23.0
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Berzosertib
|
8650 h*ng/mL
Geometric Coefficient of Variation 23.0
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Terminal Elimination Half-Life (T1/2) of Berzosertib
|
19.6 hours
Geometric Coefficient of Variation 19.9
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
CL is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as dose divided by AUC0-infinity.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Total Body Clearance (CL) of Berzosertib From Plasma
|
47.7 liter per hour
Geometric Coefficient of Variation 32.7
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz = Dose/AUC0-inf multiply Lambda z.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Apparent Volume of Distribution During the Terminal Phase (Vz) of Berzosertib
|
1340 liters
Geometric Coefficient of Variation 31.1
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Vss is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Apparent Volume of Distribution at Steady State (Vss) of Berzosertib
|
930 liters
Geometric Coefficient of Variation 24.7
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Cmax was obtained directly from the plasma concentration versus time curve. Cmax of total radioactivity was calculated in nanogram equivalents per milliliter (ng eq)/mL.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity
|
2410 (ng eq)/mL
Geometric Coefficient of Variation 19.2
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. AUC0-t was calculated in hour\*nanogram equivalents per milliliter (h\*\[ng eq/mL\]).
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
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 h*ng eq/mL
Geometric Coefficient of Variation 19.0
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Radioactivity
|
39400 h*ng eq/mL
Geometric Coefficient of Variation 19.2
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Terminal Elimination Half-Life (T1/2) of Total Radioactivity
|
64.3 hours
Geometric Coefficient of Variation 30.1
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Cmax was obtained directly from the blood concentration versus time curve.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Maximum Observed Blood Concentration (Cmax) of Total Radioactivity
|
2920 ng eq/mL
Geometric Coefficient of Variation 9.7
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Area under the blood concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
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 h*(ng eq/mL)
Geometric Coefficient of Variation 23.8
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Area Under the Blood Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Radioactivity
|
33900 h*(ng eq/mL)
Geometric Coefficient of Variation 23.1
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Terminal Elimination Half-Life (T1/2) of Total Radioactivity in Blood
|
30.6 hours
Geometric Coefficient of Variation 50.6
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Aeurine is defined as the amount of Berzosertib excreted in urine over the time interval from t1 (= start) and t2 (= end).
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Cumulative Amount of Berzosertib Dose Excreted in Urine (Aeurine)
|
41.1 milligram equivalent (mg eq)
Standard Deviation 14.8
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Feurine is defined as the amount of Berzosertib unchanged excreted in urine as percentage of the administered dose over the time interval t1 (= start) and t2 (= end).
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Percentage of Berzosertib Dose Excreted in Urine (Feurine)
|
9.84 percentage of administered dose (%)
Standard Deviation 2.74
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dosePopulation: PK Analysis Set was a subset of the SAF included all participants who received at least one dose of IMP, in Period 1 and provide at least one measurable post-dose concentration. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Renal clearance was calculated as total amount of unchanged drug excreted in the urine between times t1 and t2 (Aeurine) divided by area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Outcome measures
| Measure |
[14C]Berzosertib
n=5 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1: Renal Clearance (CLr) of Berzosertib
|
7.84 liter per hour
Standard Deviation 2.86
|
—
|
SECONDARY outcome
Timeframe: 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 16 months)Population: SAF included all participants who had received any dose of any study intervention.
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically significant findings in vital signs were reported. Clinical significance was decided by Investigator.
Outcome measures
| Measure |
[14C]Berzosertib
n=6 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
n=5 Participants
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1 and Period 2: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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 16 months)Population: SAF included all participants who had received any dose of any study intervention.
12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semi-supine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
Outcome measures
| Measure |
[14C]Berzosertib
n=6 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
n=5 Participants
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1 and Period 2: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Measurements
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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 16 months)Population: SAF included all participants who had received any dose of any study intervention.
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs. Treatment related AEs: reasonably related to the study drug/study treatment.
Outcome measures
| Measure |
[14C]Berzosertib
n=6 Participants
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
n=5 Participants
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|
|
Period 1 and Period 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs
TEAEs
|
6 Participants
|
5 Participants
|
|
Period 1 and Period 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs
Treatment Related TEAEs
|
4 Participants
|
5 Participants
|
Adverse Events
[14C]Berzosertib
Berzosertib + Topotecan
All Participants
Serious adverse events
| Measure |
[14C]Berzosertib
n=6 participants at risk
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
n=5 participants at risk
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
All Participants
n=6 participants at risk
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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. In Period 2, participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6 • 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, assessed up to 16 months
|
40.0%
2/5 • Number of events 2 • 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, assessed up to 16 months
|
33.3%
2/6 • Number of events 2 • 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, assessed up to 16 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/6 • 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, assessed up to 16 months
|
40.0%
2/5 • Number of events 2 • 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, assessed up to 16 months
|
33.3%
2/6 • Number of events 2 • 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, assessed up to 16 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/6 • 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, assessed up to 16 months
|
20.0%
1/5 • Number of events 1 • 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, assessed up to 16 months
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
|
General disorders
Disease progression
|
0.00%
0/6 • 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, assessed up to 16 months
|
20.0%
1/5 • Number of events 1 • 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, assessed up to 16 months
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
Other adverse events
| Measure |
[14C]Berzosertib
n=6 participants at risk
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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.
|
Berzosertib + Topotecan
n=5 participants at risk
Participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
|
All Participants
n=6 participants at risk
Participants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) 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. In Period 2, participants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle until disease progression or other criteria for study intervention discontinuation were met.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6 • 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, assessed up to 16 months
|
60.0%
3/5 • Number of events 6 • 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, assessed up to 16 months
|
50.0%
3/6 • Number of events 6 • 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, assessed up to 16 months
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/6 • 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, assessed up to 16 months
|
60.0%
3/5 • Number of events 9 • 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, assessed up to 16 months
|
50.0%
3/6 • Number of events 9 • 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, assessed up to 16 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/6 • 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, assessed up to 16 months
|
40.0%
2/5 • Number of events 2 • 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, assessed up to 16 months
|
33.3%
2/6 • Number of events 2 • 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, assessed up to 16 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/6 • 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, assessed up to 16 months
|
40.0%
2/5 • Number of events 4 • 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, assessed up to 16 months
|
33.3%
2/6 • Number of events 4 • 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, assessed up to 16 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6 • 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, assessed up to 16 months
|
20.0%
1/5 • Number of events 1 • 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, assessed up to 16 months
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • 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, assessed up to 16 months
|
20.0%
1/5 • Number of events 1 • 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, assessed up to 16 months
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
|
General disorders
Asthenia
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
0.00%
0/5 • 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, assessed up to 16 months
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
|
General disorders
Infusion site reaction
|
66.7%
4/6 • Number of events 4 • 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, assessed up to 16 months
|
0.00%
0/5 • 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, assessed up to 16 months
|
66.7%
4/6 • Number of events 4 • 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, assessed up to 16 months
|
|
Infections and infestations
Respiratory tract infection
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
0.00%
0/5 • 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, assessed up to 16 months
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
|
Injury, poisoning and procedural complications
Transfusion related complication
|
0.00%
0/6 • 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, assessed up to 16 months
|
20.0%
1/5 • Number of events 1 • 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, assessed up to 16 months
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/6 • 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, assessed up to 16 months
|
20.0%
1/5 • Number of events 1 • 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, assessed up to 16 months
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
0.00%
0/5 • 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, assessed up to 16 months
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
0.00%
0/5 • 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, assessed up to 16 months
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
|
Nervous system disorders
Headache
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
0.00%
0/5 • 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, assessed up to 16 months
|
16.7%
1/6 • Number of events 1 • 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, assessed up to 16 months
|
Additional Information
Communication Center
Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place