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Percentage of Participants Who Died
Time frame: From Day 1 to death from any cause, up to the study completion date (approximately 43 months)
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Overall Survival (OS)
Time frame: From Day 1 to death from any cause, up to the study completion date (approximately 43 months)
OS is defined as the time from first study drug administration to death from any cause.
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Percentage of Participants With PFS Event of Disease Progression, as Per Investigator Assessment According to RECIST v. 1.1, or Death
Time frame: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)
PFS is defined as the time from first study drug administration to first documented disease progression, based on investigator assessment using RECIST, v1.1, or death from any cause during the study, whichever occurs first. Disease progression is defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.
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Progression-Free Survival (PFS) as Per Investigator Assessment According to RECIST v. 1.1
Time frame: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)
PFS is defined as the time from first study drug administration to first documented disease progression, based on investigator assessment using RECIST, v1.1, or death from any cause during the study, whichever occurs first. Disease progression is defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.
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Percentage of Participants With DOR Event of Disease Progression, Assessed According to RECIST v1.1
Time frame: From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)
DOR is defined as the time from the initial documentation of response (CR or PR using RECIST, v1.1) to documented disease progression using RECIST v1.1 or death from any cause during the study. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.
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Duration of Objective Response (DOR) Assessed According to RECIST v1.1
Time frame: From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)
DoR is defined as the time from the initial documentation of response (CR or PR using RECIST, v1.1) to documented disease progression using RECIST v1.1 or death from any cause during the study. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.
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Percentage of Participants With Clinical Benefit as Per Investigator Assessment According to RECIST, v1.1
Time frame: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)
Clinical benefit is defined as having a CR or PR or stable disease (using RECIST, v1.1) at 6 months. Participants with no post-baseline response assessment are considered as experiencing no clinical benefit. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum while in the study. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.
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Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Time frame: From Day 1 to 30 days after last dose of study drug, up to the study completion date (approximately 43 months)
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, whether or not considered related to the study drug. A SAE is any experience that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant.
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Maximum Observed Concentration (Cmax) for Trastuzumab Emtansine and Total Trastuzumab
Time frame: Pre-dose (within 2 days) and 30 minutes (min) after end of infusion (infusion length= 100 min or less) on Day 1 of Cycles 1 and 3 (one cycle=21 days); at treatment discontinuation/early termination, up to primary analysis, approx. 22 months
Cmax is the 0-21 day maximum observed concentration of a drug and was measured in blood serum.
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AUCinf for Trastuzumab Emtansine and Total Trastuzumab
Time frame: Pre-dose & 30 minutes (min) post-infusion (inf.) on Day (D) 1 of Cycles (C) 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D1 of C2 & D1 of C 4 (C=21 D); at discontin./termination, up to primary analysis, approx. 22 months
AUC (from zero to infinity) represents the total drug exposure over time in blood serum.
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Elimination Half-Life (t1/2) for Trastuzumab Emtansine and Total Trastuzumab
Time frame: Pre-dose & 30 minutes (min) post-infusion (inf.) on D 1 of C 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D 1 of C 4 (C=21 days); at treatment discontin./early termination, up to primary analysis, approx. 22 months
t1/2 is the time required for the drug serum concentration to be reduced to half.
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Volume of Distribution (Vss) for Trastuzumab Emtansine and Total Trastuzumab
Time frame: Pre-dose & 30 minutes (min) post-infusion (inf.) on D1 of C1 & 3; post- inf. on D2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D1 of C 4 (C=21 days); at treatment discontin/early termination, up to primary analysis, approx. 22 months
Vss is the volume of distribution of study drug at steady state.
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Clearance (CL) for Trastuzumab Emtansine and Total Trastuzumab
Time frame: Pre-dose & 30 minutes (min) post-infusion (inf.) on D 1 of C 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D 1 of C 4 (C=21 days); at treatment discontin/early termination, up to primary analysis, approx. 22 months
CL is a measure of the body's elimination of a drug from blood serum over time.
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Maximum Observed Concentration (Cmax) for N2'- Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1)
Time frame: Pre-dose (within 2 days) and 30 minutes (min) after end of infusion (infusion length= 100 min or less) on Day 1 of Cycle 1 (one cycle=21 days); at treatment discontinuation/early termination,up to primary analysis, approx. 22 months
Cmax is the maximum observed concentration of a drug and was measured in blood plasma.
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Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)
Time frame: Pre-dose (within 2 days) on Day 1 of Cycles 1 and 3; at treatment discontinuation/early termination,up to primary analysis, approx. 22 months
The presence of ADAs in blood serum is an indication of the body's immune response to a drug.