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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-004231-25 | EudraCT Number |
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| Name | Class |
|---|---|
| Merck KGaA, Darmstadt, Germany | INDUSTRY |
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The main purpose of this study is to assess efficacy, safety, tolerability and pharmacokinetics (PK) of Berzosertib in combination with Topotecan in participants with relapsed, platinum-resistant small-cell lung cancer (SCLC). This study will be conducted in two parts: safety run-in part and main part. The safety run-in part will be conducted in Japan.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Safety run-in Part (Dose Level1 [DL 1]): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2 | Experimental | Participants received Berzosertib at a dose of 105 milligrams per square meter (mg/m^2 ) intravenously on Day 2 and Day 5 of each 21-daycycle in combination with Topotecan at a dose of 1.25mg/m^2 intravenously on Days1 through 5 of each 21-day cycle in DL1 of safety run-in part until disease progression or other criteria for study intervention discontinuation are met. |
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| Safety run-in Part (DL2) +Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2 | Experimental | Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL 1 and DL 2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Berzosertib | Drug | Participants received Berzosertib at a dose of 105 milligrams per square meter (mg/m^2 ) intravenously on Day 2 and Day 5 of each 21-day cycle until disease progression or other criteria for study intervention discontinuation are met. |
| Measure | Description | Time Frame |
|---|---|---|
| Main Part: Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC) | Objective response rate was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD). CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. | Time from first administration of study treatment up to 27.7 months |
| Safety Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs) | DLT is defined as drug-related: Neutropenia Grade 4 for greater than (>) 7 days' duration; Febrile neutropenia (that is [i.e.] absolute neutrophil count less than (< ) 1000 per millimeter cube (mm^3) with single temperature of > 38.3°degree Celsius or a sustained temperature of greater than or equal to (>=) 38 degree Celsius for more than 1 hour; Infection (documented clinically or microbiologically) with Grades 3 or 4 neutropenia; Thrombocytopenia >= Grade 3; Grade >= 3 non-hematological AEs. | Up to Cycle 1 Day 21 (each cycle is of 21 days) |
| Safety Run-in Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs | An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs is defined as reasonably related to the study intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Main Part: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC) | DoR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Providence Medical Foundation | Santa Rosa | California | 95403 | United States | ||
| St Joseph Heritage Healthcare |
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| Label | URL |
|---|---|
| Trial Awareness and Transparency website | View source |
| US Medical Information website, Medical Resources | View source |
| DDRiver website |
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We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports 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 bit.ly/IPD21
Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
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| ID | Title | Description |
|---|---|---|
| FG000 | Safety run-in Part (Dose Level 1 [DL 1]): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2 | Participants received Berzosertib at a dose of 105 milligrams per square meter (mg/m^2 ) intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 of safety run-in part until disease progression or other criteria for study intervention discontinuation are met. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 21, 2021 | Jul 17, 2024 |
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| Berzosertib | Drug | Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle in DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
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| Topotecan | Drug | Participants received Topotecan at a dose of 1.25 mg/m^2 intravenously on Days 1 through 5 of each 21-day cycle in DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
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| Time from first administration of study treatment up to 27.7 months |
| Safety Run-in Part: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinical significance was decided by Investigator. | Time from first administration of study treatment up to 27.7 months |
| Safety Run-in Part: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was decided by investigator. Number of participants with clinically significant changes from baseline in 12-Lead ECGs were reported. | Time from first administration of study treatment up to 27.7 months |
| Safety Run-in Part: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) | The laboratory measurements included hematology and biochemistry. Number of participants with clinically significant abnormalities with Grade greater than or equals to (>=) 3 in laboratory values reported as TEAEs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 graded from Grade 1 to 5. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Clinically Significance was decided by investigator. | Time from first administration of study treatment up to 27.7 months |
| From first documented objective response to PD or death due to any cause, assessed up to 27.7 months |
| Main Part: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC) | PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. | Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed up to 27.7 months |
| Main Part: Overall Survival (OS) | Overall survival is defined as the time from first administration of study treatment to the date of death. | Time from first administration of study treatment to the date of death, assessed up to 27.7 months |
| Main Part: Change From Baseline in Physical Functioning Measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | The EORTC QLQ-C30 is a participant completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a global health status/QoL scale. For the physical functioning scale, subjects self-rated levels of difficulty in doing strenuous activities, taking a walk, how much they needed to stay in bed or a chair, or needed help with eating, dressing, bathing, using the toilet. The physical functioning scale had 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0 to 100. Higher scores indicate better functioning. A positive change from baseline indicates improvement in physical functioning. | Baseline (Cycle 1 Day 1), end of treatment (up to 62 weeks). Each cycle is of 21 days |
| Main Part: Number of Participants Who Improved, Worsened or Remained Stable in European Organization for the Research and Treatment of Cancer Quality of Life and Lung Cancer Specific Questionnaire (EORTC QLQ-LC13) | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms, and improvement was defined as a decrease of at least 10 points, worsening was defined as an increase of at least 10 points. All scales which had not improved nor worsened were considered stable. | Baseline (Cycle 1 Day 1), end of treatment (up to 62 weeks). Each cycle is of 21 days |
| Main Part: Change From Baseline in Health State as Measured by Visual Analogue Scale (VAS) Component of European Quality of Life 5-dimensions 5 Level Scale (EQ-5D-5L) | EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100, where 0 is the worst health you can imagine and 100 is the best health you can imagine. | Baseline (Cycle 1 Day 1), end of treatment (up to 62 weeks). Each cycle is of 21 days |
| Main Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs | An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs is defined as reasonably related to the study intervention. | Time from first administration of study treatment up to 27.7 months |
| Main Part: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinical significance was decided by Investigator. | Time from first administration of study treatment up to 27.7 months |
| Main Part: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was decided by investigator. Number of participants with clinically significant changes from baseline in 12-Lead ECGs were reported. | Time from first administration of study treatment up to 27.7 months |
| Main Part: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) | The laboratory measurements included hematology and biochemistry. Number of participants with clinically significant abnormalities with Grade greater than or equals to (>=) 3 in laboratory values reported as TEAEs as per NCI-CTCAE, v5.0 graded from Grade 1 to 5. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Clinically Significance was decided by investigator. The laboratory assessments were graded according to NCI-CTCAE version 5.0 and data for individual clinically significant abnormalities (Grade >= 3) was extracted using data source (ADLBHEMA). The data categorized here may not necessarily be considered as TEAE by the investigator during the reporting of TEAEs and there is no correlation between the grade >=3 treatment related TEAEs hematology parameters and the TEAEs in the AE module. | Time from first administration of study treatment up to 27.7 months |
| Safety Run-in Part: Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator | Objective response rate was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD). CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. | Time from first administration of study treatment up to 27.7 months |
| Safety Run-in Part: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator | DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. | Time from first administration of study treatment up to 27.7 months |
| Safety Run-in Part: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator | PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. | Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed up to 27.7 months |
| Safety Run-in Part: Overall Survival (OS) | Overall survival is defined as the time from first administration of study treatment to the date of death. | Time from first administration of study treatment to the date of death, assessed up to 27.7 months |
| Safety Run-in Part: Change From Baseline in Physical Functioning Measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | The EORTC QLQ-C30 is a participant completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a global health status/QoL scale. For the physical functioning scale, subjects self-rated levels of difficulty in doing strenuous activities, taking a walk, how much they needed to stay in bed or a chair, or needed help with eating, dressing, bathing, using the toilet. The physical functioning scale had 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0 to 100. Higher scores indicate better functioning. A positive change from baseline indicates improvement in physical functioning. | Baseline (Cycle 1 Day 1), end of treatment (up to 64 weeks). Each cycle is of 21 days |
| Safety Run-in Part: Change From Baseline in Cough, Dyspnea and Chest Pain Measured by European Organization for the Research and Treatment of Cancer Quality of Life and Lung Cancer Specific Questionnaire (EORTC QLQ-LC13) | EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items). | Baseline (Cycle 1 Day 1), end of treatment (up to 64 weeks). Each cycle is of 21 days |
| Safety Run-in Part: Change From Baseline in Health State as Measured by Visual Analogue Scale (VAS) Component of European Quality of Life 5-dimensions 5 Level Scale (EQ-5D-5L) | EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100, where 0 is the worst health you can imagine and 100 is the best health you can imagine. | Baseline (Cycle 1 Day 1), end of treatment (up to 64 weeks). Each cycle is of 21 days |
| Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) of Berzosertib | 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. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast/Dose) of Berzosertib | AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose. AUC0-t/dose was measured in hour*nanogram per milliliter per milligram (h*ng/mL/mg). | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Berzosertib | 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. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of Berzosertib | AUC0-inf/Dose was defined as AUC extrapolated to infinity divided by dose. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero to 48 Hours (AUC0-48h) of Berzosertib | Area under the concentration-time curve from pre-dose (time 0) to 48 hours post-dose calculated using the linear-log trapezoidal rule | Pre-dose, 1, 2, 3, 4, 8, 24 and 48 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to 48 Hours (AUC0-48h/Dose) of Berzosertib | AUC0-48 hour/Dose was defined as AUC from time of dosing to 48 hours divided by dose. | Pre-dose, 1, 2, 3, 4, 8, 24 and 48 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72h) of Berzosertib | Area under the concentration-time curve from pre-dose (time 0) to 72 hours post-dose calculated using the linear-log trapezoidal rule | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72h/Dose) of Berzosertib | AUC0-72 hour/Dose was defined as AUC from time of dosing to 72 hours divided by dose. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Berzosertib | Cmax was obtained directly from the plasma concentration versus time curve. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of Berzosertib | Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in nanogram per milliliter per milligram (ng/mL/mg). | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Plasma Observed Concentration at the End of the Infusion (Ceoi) of Berzosertib | Ceoi was the observed concentration at the end of the infusion period. This was taken directly from the observed Berzosetib concentration-time data. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2; Pre-dose, 1 and 1.5 hours after dose on Cycle 1 Day 5 (each cycle is of 21 days) |
| Safety Run-in Part: Plasma Observed Concentration Immediately Before Next Dosing (Ctrough) of Berzosertib | Ctrough was the plasma concentration observed immediately before next dosing. | Pre-dose on Cycle 1 Day 5 (each cycle is of 21 days) |
| Safety Run-in Part: Apparent Total Body Clearance (CL) of Berzosertib | CL was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Accumulation Ratio for Maximum Observed Plasma Concentration [Racc(Cmax)] of Berzosertib | Accumulation ratio of Cmax was calculated as Cmax after dosing on Day 5 divided by Cmax after dosing on Day 2 of Cycle 1. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2; Pre-dose, 1 and 1.5 hours after dose on Cycle 1 Day 5 (each cycle is of 21 days) |
| Safety Run-in Part: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Berzosertib | Tmax was obtained directly from the plasma concentration versus time curve. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Apparent Terminal Half-life (t1/2) of Berzosertib | 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. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Last Sampling Time (Tlast) of Berzosertib | tlast is defined as the last sampling time at which the concentration is at or above the lower limit of quantification. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Safety Run-in Part: Apparent Volume of Distribution During Terminal Phase (Vz) of Berzosertib | Vz: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| Santa Rosa |
| California |
| 95403 |
| United States |
| Cotton-O'Neil Clinical Research Center, Hematology and Oncology | Topeka | Kansas | 66606 | United States |
| National Cancer Institute | Bethesda | Maryland | 20892 | United States |
| Cancer & Hematology Centers of Western Michigan | Grand Rapids | Michigan | 49546 | United States |
| MidAmerica Cancer Care | Kansas City | Missouri | 64114 | United States |
| NJ Center for Cancer Research | Brick | New Jersey | 08724 | United States |
| Southeastern Medical Oncology Center | Goldsboro | North Carolina | 27534 | United States |
| FirstHealth of the Carolinas, Inc. | Pinehurst | North Carolina | 28374 | United States |
| Summa Health | Akron | Ohio | 44304 | United States |
| Toledo Clinic | Toledo | Ohio | 43623 | United States |
| Millennium Physicians Association, LLP | Houston | Texas | 77090 | United States |
| Centre Hospitalier de l'Ardenne | Arlon | Belgium |
| Institut Jules Bordet - Department of Institut Jules Bordet | Brussels | Belgium |
| Universitair Ziekenhuis Gent | Ghent | Belgium |
| AZ Delta | Roeselare | Belgium |
| CHU UCL Namur - Mont-Godinne | Yvoir | Belgium |
| Beijing Cancer Hospital | Beijing | China |
| Jilin Cancer Hospital | Changchun | China |
| Sichuan Cancer Hospital | Chengdu | China |
| West China Hospital, Sichuan University | Chengdu | China |
| Jiangsu Province Hospital | Nanjing | China |
| Liaoning Cancer Hospital & Institute | Shenyang | China |
| Union Hospital of Tongji Medical College, Huazhong University of Science and Technology | Wuhan | China |
| The First Affiliated Hospital of Xi'an Jiaotong University | Xi'an | China |
| The First Affiliated Hospital of Zhejiang University school of medicine | Zhejiang | China |
| Institut Bergonié | Bordeaux | France |
| Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie | Créteil | France |
| Hopital Albert Calmette - CHU Lille - service de pneumologie et immuno allergologie | Lille | France |
| CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale | Poitiers | France |
| CHU Nantes - Hôpital Guillaume et René Laënnec - Service de Pneumologie | Saint-Herblain | France |
| CHU de Strasbourg - Nouvel Hôpital Civil - Service de Pneumologie | Strasbourg | France |
| IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST | Meldola | Italy |
| Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda) | Milan | Italy |
| Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello) | Pisa | 56124 | Italy |
| Istituto Nazionale Tumori Regina Elena IRCCS | Roma | 00144 | Italy |
| Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica | Rome | Italy |
| National Cancer Center Hospital | Chūōku | Japan |
| Kansai Medical University Hospital | Hirakata-shi | Japan |
| National Cancer Center Hospital East | Kashiwa-shi | Japan |
| Cancer Institute Hospital of JFCR | Kōtoku | Japan |
| Kindai University Hospital | Osaka | Japan |
| Kurume University Hospital | Osaka | Japan |
| Osaka Medical and Pharmaceutical University Hospital | Takatsuki-shi | Japan |
| Hospital Clinic de Barcelona | Barcelona | Spain |
| Hospital Universitari Vall d'Hebron | Barcelona | Spain |
| Hospital Universitario 12 de Octubre | Madrid | Spain |
| Hospital Universitario La Paz | Madrid | Spain |
| Hospital Clinico Universitario Virgen de la Victoria - Oncology Service | Málaga | Spain |
| Hospital Universitario Virgen de la Victoria | Málaga | Spain |
| Hospital Universitario Virgen Macarena | Seville | Spain |
| FG001 | Safety run-in Part (DL2) + Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2 | Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
| COMPLETED |
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| NOT COMPLETED |
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Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Safety run-in Part (Dose Level 1 [DL 1]): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2 | Participants received Berzosertib at a dose of 105 milligrams per square meter (mg/m^2 ) intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 of safety run-in part until disease progression or other criteria for study intervention discontinuation are met. |
| BG001 | Safety run-in Part (DL2) + Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2 | Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
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| Primary | Main Part: Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC) | Objective response rate was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD). CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. | Full Analysis Set (FAS) included all participants who were administered at least 1 dose of berzosertib. | Posted | Number | 95% Confidence Interval | percentage of participants | Time from first administration of study treatment up to 27.7 months |
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| Primary | Safety Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs) | DLT is defined as drug-related: Neutropenia Grade 4 for greater than (>) 7 days' duration; Febrile neutropenia (that is [i.e.] absolute neutrophil count less than (< ) 1000 per millimeter cube (mm^3) with single temperature of > 38.3°degree Celsius or a sustained temperature of greater than or equal to (>=) 38 degree Celsius for more than 1 hour; Infection (documented clinically or microbiologically) with Grades 3 or 4 neutropenia; Thrombocytopenia >= Grade 3; Grade >= 3 non-hematological AEs. | DLT analysis set: all participants who were administered any dose of any study intervention in Safety Run-in Part in Japan and meet at least one of the following criteria: Received at least 80% of planned cumulative dose of study intervention during the DLT and completed the DLT period. The final decision on evaluability is made by the SMC; Experienced at least 1 DL T during the DLT period, regardless of the administered cumulative dose of study intervention and completion of the DLT period. | Posted | Count of Participants | Participants | Up to Cycle 1 Day 21 (each cycle is of 21 days) |
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| Primary | Safety Run-in Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs | An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs is defined as reasonably related to the study intervention. | Safety (SAF) Analysis Set included all participants who were administered at least 1 dose of berzosertib. | Posted | Count of Participants | Participants | Time from first administration of study treatment up to 27.7 months |
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| Primary | Safety Run-in Part: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinical significance was decided by Investigator. | Safety (SAF) Analysis Set included all participants who were administered at least 1 dose of berzosertib. | Posted | Count of Participants | Participants | Time from first administration of study treatment up to 27.7 months |
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| Primary | Safety Run-in Part: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was decided by investigator. Number of participants with clinically significant changes from baseline in 12-Lead ECGs were reported. | Safety (SAF) Analysis Set included all participants who were administered at least 1 dose of berzosertib. | Posted | Count of Participants | Participants | Time from first administration of study treatment up to 27.7 months |
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| Primary | Safety Run-in Part: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) | The laboratory measurements included hematology and biochemistry. Number of participants with clinically significant abnormalities with Grade greater than or equals to (>=) 3 in laboratory values reported as TEAEs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 graded from Grade 1 to 5. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Clinically Significance was decided by investigator. | Safety (SAF) Analysis Set included all participants who were administered at least 1 dose of berzosertib. | Posted | Count of Participants | Participants | Time from first administration of study treatment up to 27.7 months |
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| Secondary | Main Part: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC) | DoR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. | FAS was used. Due to small number of participants with a response, data was not summarized; however, individual participant data is reported for this outcome measure. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome measure and "number analyzed" = specific participants evaluated in the arm. | Posted | Number | months | From first documented objective response to PD or death due to any cause, assessed up to 27.7 months |
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| Secondary | Main Part: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC) | PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. | Full Analysis Set (FAS) included all participants who were administered at least 1 dose of berzosertib. | Posted | Median | 95% Confidence Interval | months | Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed up to 27.7 months |
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| Secondary | Main Part: Overall Survival (OS) | Overall survival is defined as the time from first administration of study treatment to the date of death. | Full Analysis Set (FAS) included all participants who were administered at least 1 dose of berzosertib. | Posted | Median | 95% Confidence Interval | months | Time from first administration of study treatment to the date of death, assessed up to 27.7 months |
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| Secondary | Main Part: Change From Baseline in Physical Functioning Measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | The EORTC QLQ-C30 is a participant completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a global health status/QoL scale. For the physical functioning scale, subjects self-rated levels of difficulty in doing strenuous activities, taking a walk, how much they needed to stay in bed or a chair, or needed help with eating, dressing, bathing, using the toilet. The physical functioning scale had 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0 to 100. Higher scores indicate better functioning. A positive change from baseline indicates improvement in physical functioning. | Full Analysis Set (FAS) included all participants who were administered at least 1 dose of berzosertib. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Cycle 1 Day 1), end of treatment (up to 62 weeks). Each cycle is of 21 days |
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| Secondary | Main Part: Number of Participants Who Improved, Worsened or Remained Stable in European Organization for the Research and Treatment of Cancer Quality of Life and Lung Cancer Specific Questionnaire (EORTC QLQ-LC13) | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms, and improvement was defined as a decrease of at least 10 points, worsening was defined as an increase of at least 10 points. All scales which had not improved nor worsened were considered stable. | Full Analysis Set (FAS) included all participants who were administered at least 1 dose of berzosertib. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Count of Participants | Participants | Baseline (Cycle 1 Day 1), end of treatment (up to 62 weeks). Each cycle is of 21 days |
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| Secondary | Main Part: Change From Baseline in Health State as Measured by Visual Analogue Scale (VAS) Component of European Quality of Life 5-dimensions 5 Level Scale (EQ-5D-5L) | EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100, where 0 is the worst health you can imagine and 100 is the best health you can imagine. | Full Analysis Set (FAS) included all participants who were administered at least 1 dose of berzosertib. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Cycle 1 Day 1), end of treatment (up to 62 weeks). Each cycle is of 21 days |
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| Secondary | Main Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs | An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs is defined as reasonably related to the study intervention. | Safety (SAF) Analysis Set included all participants who were administered at least 1 dose of berzosertib. | Posted | Count of Participants | Participants | Time from first administration of study treatment up to 27.7 months |
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| Secondary | Main Part: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinical significance was decided by Investigator. | Safety (SAF) Analysis Set included all participants who were administered at least 1 dose of berzosertib. | Posted | Count of Participants | Participants | Time from first administration of study treatment up to 27.7 months |
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| Secondary | Main Part: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was decided by investigator. Number of participants with clinically significant changes from baseline in 12-Lead ECGs were reported. | Safety (SAF) Analysis Set included all participants who were administered at least 1 dose of berzosertib. | Posted | Count of Participants | Participants | Time from first administration of study treatment up to 27.7 months |
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| Secondary | Main Part: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) | The laboratory measurements included hematology and biochemistry. Number of participants with clinically significant abnormalities with Grade greater than or equals to (>=) 3 in laboratory values reported as TEAEs as per NCI-CTCAE, v5.0 graded from Grade 1 to 5. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Clinically Significance was decided by investigator. The laboratory assessments were graded according to NCI-CTCAE version 5.0 and data for individual clinically significant abnormalities (Grade >= 3) was extracted using data source (ADLBHEMA). The data categorized here may not necessarily be considered as TEAE by the investigator during the reporting of TEAEs and there is no correlation between the grade >=3 treatment related TEAEs hematology parameters and the TEAEs in the AE module. | Safety (SAF) Analysis Set included all participants who were administered at least 1 dose of berzosertib. | Posted | Count of Participants | Participants | Time from first administration of study treatment up to 27.7 months |
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| Secondary | Safety Run-in Part: Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator | Objective response rate was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD). CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. | Full Analysis Set (FAS) included all participants who were administered at least 1 dose of berzosertib. | Posted | Number | 95% Confidence Interval | percentage of participants | Time from first administration of study treatment up to 27.7 months |
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| Secondary | Safety Run-in Part: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator | DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. | Full Analysis Set (FAS) included all participants who were administered at least 1 dose of berzosertib. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Number | months | Time from first administration of study treatment up to 27.7 months |
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| Secondary | Safety Run-in Part: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator | PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. | Full Analysis Set (FAS) included all participants who were administered at least 1 dose of berzosertib. | Posted | Median | Full Range | months | Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed up to 27.7 months |
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| Secondary | Safety Run-in Part: Overall Survival (OS) | Overall survival is defined as the time from first administration of study treatment to the date of death. | Full Analysis Set (FAS) included all participants who were administered at least 1 dose of berzosertib. | Posted | Median | 95% Confidence Interval | months | Time from first administration of study treatment to the date of death, assessed up to 27.7 months |
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| Secondary | Safety Run-in Part: Change From Baseline in Physical Functioning Measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | The EORTC QLQ-C30 is a participant completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a global health status/QoL scale. For the physical functioning scale, subjects self-rated levels of difficulty in doing strenuous activities, taking a walk, how much they needed to stay in bed or a chair, or needed help with eating, dressing, bathing, using the toilet. The physical functioning scale had 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0 to 100. Higher scores indicate better functioning. A positive change from baseline indicates improvement in physical functioning. | As per changes in planned analysis, the outcome measure related to quality of life for safety run-in part was not assessed. | Posted | Baseline (Cycle 1 Day 1), end of treatment (up to 64 weeks). Each cycle is of 21 days |
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| Secondary | Safety Run-in Part: Change From Baseline in Cough, Dyspnea and Chest Pain Measured by European Organization for the Research and Treatment of Cancer Quality of Life and Lung Cancer Specific Questionnaire (EORTC QLQ-LC13) | EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items). | As per changes in planned analysis, the outcome measure related to quality of life for safety run-in part was not assessed. | Posted | Baseline (Cycle 1 Day 1), end of treatment (up to 64 weeks). Each cycle is of 21 days |
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| Secondary | Safety Run-in Part: Change From Baseline in Health State as Measured by Visual Analogue Scale (VAS) Component of European Quality of Life 5-dimensions 5 Level Scale (EQ-5D-5L) | EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100, where 0 is the worst health you can imagine and 100 is the best health you can imagine. | As per changes in planned analysis, the outcome measure related to quality of life for safety run-in part was not assessed. | Posted | Baseline (Cycle 1 Day 1), end of treatment (up to 64 weeks). Each cycle is of 21 days |
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| Secondary | Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) of Berzosertib | 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. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
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| Secondary | Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast/Dose) of Berzosertib | AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose. AUC0-t/dose was measured in hour*nanogram per milliliter per milligram (h*ng/mL/mg). | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL/mg | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
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| Secondary | Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Berzosertib | 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. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
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| Secondary | Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of Berzosertib | AUC0-inf/Dose was defined as AUC extrapolated to infinity divided by dose. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL/mg | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
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| Secondary | Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero to 48 Hours (AUC0-48h) of Berzosertib | Area under the concentration-time curve from pre-dose (time 0) to 48 hours post-dose calculated using the linear-log trapezoidal rule | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Pre-dose, 1, 2, 3, 4, 8, 24 and 48 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
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| Secondary | Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to 48 Hours (AUC0-48h/Dose) of Berzosertib | AUC0-48 hour/Dose was defined as AUC from time of dosing to 48 hours divided by dose. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL/mg | Pre-dose, 1, 2, 3, 4, 8, 24 and 48 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
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| Secondary | Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72h) of Berzosertib | Area under the concentration-time curve from pre-dose (time 0) to 72 hours post-dose calculated using the linear-log trapezoidal rule | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
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| Secondary | Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72h/Dose) of Berzosertib | AUC0-72 hour/Dose was defined as AUC from time of dosing to 72 hours divided by dose. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL/mg | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
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| Secondary | Safety Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Berzosertib | Cmax was obtained directly from the plasma concentration versus time curve. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| |||||||||||||||||||||||||||
| Secondary | Safety Run-in Part: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of Berzosertib | Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in nanogram per milliliter per milligram (ng/mL/mg). | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL/mg | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| |||||||||||||||||||||||||||
| Secondary | Safety Run-in Part: Plasma Observed Concentration at the End of the Infusion (Ceoi) of Berzosertib | Ceoi was the observed concentration at the end of the infusion period. This was taken directly from the observed Berzosetib concentration-time data. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2; Pre-dose, 1 and 1.5 hours after dose on Cycle 1 Day 5 (each cycle is of 21 days) |
| |||||||||||||||||||||||||||
| Secondary | Safety Run-in Part: Plasma Observed Concentration Immediately Before Next Dosing (Ctrough) of Berzosertib | Ctrough was the plasma concentration observed immediately before next dosing. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose on Cycle 1 Day 5 (each cycle is of 21 days) |
| |||||||||||||||||||||||||||
| Secondary | Safety Run-in Part: Apparent Total Body Clearance (CL) of Berzosertib | CL was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| |||||||||||||||||||||||||||
| Secondary | Safety Run-in Part: Accumulation Ratio for Maximum Observed Plasma Concentration [Racc(Cmax)] of Berzosertib | Accumulation ratio of Cmax was calculated as Cmax after dosing on Day 5 divided by Cmax after dosing on Day 2 of Cycle 1. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2; Pre-dose, 1 and 1.5 hours after dose on Cycle 1 Day 5 (each cycle is of 21 days) |
| |||||||||||||||||||||||||||
| Secondary | Safety Run-in Part: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Berzosertib | Tmax was obtained directly from the plasma concentration versus time curve. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Median | Full Range | hours | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| |||||||||||||||||||||||||||
| Secondary | Safety Run-in Part: Apparent Terminal Half-life (t1/2) of Berzosertib | 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. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| |||||||||||||||||||||||||||
| Secondary | Safety Run-in Part: Last Sampling Time (Tlast) of Berzosertib | tlast is defined as the last sampling time at which the concentration is at or above the lower limit of quantification. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
| |||||||||||||||||||||||||||
| Secondary | Safety Run-in Part: Apparent Volume of Distribution During Terminal Phase (Vz) of Berzosertib | Vz: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | Pharmacokinetic Analysis Set (PKS) included all participants who were administered at least 1 complete infusion of berzosertib in the Safety Run-in Part in Japan and for whom at least 1 quantifiable post-dose plasma concentration of berzosertib was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters | Pre-dose, 1, 2, 3, 4, 8, 24, 48 and 72 hours after dose on Cycle 1 Day 2 (each cycle is of 21 days) |
|
Time from first administration of study treatment up to 27.7 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Safety run-in Part (Dose Level 1 [DL 1]): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2 | Participants received Berzosertib at a dose of 105 milligrams per square meter (mg/m^2 ) intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 of safety run-in part until disease progression or other criteria for study intervention discontinuation are met. | 1 | 3 | 0 | 3 | 3 | 3 |
| EG001 | Safety run-in Part (DL2) + Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2 | Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. | 63 | 73 | 31 | 73 | 70 | 73 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Myelosuppression | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Vestibular disorder | Ear and labyrinth disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Liver injury | Hepatobiliary disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Enterococcal sepsis | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Lung abscess | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pneumonia pneumococcal | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Serratia sepsis | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Coagulopathy | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Myelosuppression | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Vestibular disorder | Ear and labyrinth disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Immune-mediated hypothyroidism | Endocrine disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Conjunctival pallor | Eye disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Eye discharge | Eye disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Macular oedema | Eye disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Haemorrhoids thrombosed | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Lip dry | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Oral disorder | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Tooth loss | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Face oedema | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Generalised oedema | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hyperthermia | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Injection site pruritus | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Secretion discharge | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Swelling face | General disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hepatic pain | Hepatobiliary disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Liver injury | Hepatobiliary disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Bronchiolitis | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Herpes zoster reactivation | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Compression fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 26.0 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 26.0 | Non-systematic Assessment |
| |
| Radiation oesophagitis | Injury, poisoning and procedural complications | MedDRA 26.0 | Non-systematic Assessment |
| |
| Radiation pneumonitis | Injury, poisoning and procedural complications | MedDRA 26.0 | Non-systematic Assessment |
| |
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Non-systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood lactic acid increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood magnesium decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood phosphorus decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| CD4/CD8 ratio decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Creatinine renal clearance decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Platelet count increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Urine output decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Electrolyte imbalance | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypochloraemia | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Non-systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Non-systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Non-systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hemianopia homonymous | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Transient aphasia | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Device malfunction | Product Issues | MedDRA 26.0 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Choluria | Renal and urinary disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Aphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Dyspnoea paroxysmal nocturnal | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Sputum discoloured | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pallor | Vascular disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDRA 26.0 | Non-systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@emdgroup.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 17, 2023 | Jul 17, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D055752 | Small Cell Lung Carcinoma |
| D009477 | Hereditary Sensory and Autonomic Neuropathies |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D009421 | Nervous System Malformations |
| D009422 | Nervous System Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D011115 | Polyneuropathies |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
Not provided
Not provided
| ID | Term |
|---|---|
| C000598331 | berzosertib |
| D019772 | Topotecan |
| ID | Term |
|---|---|
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG001 |
| Safety run-in Part (DL2) + Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2 |
Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
|
|
Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
|
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| Units |
|---|
| Counts |
|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
|
Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
|
|
| OG001 | Safety run-in Part (DL2) + Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2 | Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG001 |
| Safety run-in Part (DL2) + Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2 |
Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
|
Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
|
|
|
|
|
|
Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| OG001 |
| Safety run-in Part (DL2) + Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2 |
Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
|
|
|
|
|
|
|
|
|
|
Participants received Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle 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 DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met. |
|
|