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    Clinical Trial Results:
    A Randomized, Open-Label, Multicenter, Phase II Trial Evaluating the Safety and Activity of DNIB0600A Compared to Pegylated Liposomal Doxorubicin Administered Intravenously to Patients With Platinum-Resistant Ovarian Cancer

    Summary
    EudraCT number
    		 2012-005776-34
    Trial protocol
    		 GB   FR   PL   ES   BE  
    Global end of trial date
    17 Aug 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Aug 2017
    First version publication date
    31 Aug 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GO28609
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01991210
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
    Scientific contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    17 Aug 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Aug 2016
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin (PLD) in participants with platinum-resistant ovarian cancer (PROC) as assessed by progression-free survival (PFS) in participants with sodium-dependent phosphate co-transporter (NaPi2b)-high tumors as well as in the overall participant population
    Protection of trial subjects
    The study was conducted in full conformance with the International Conference on Harmonization (ICH) E6 guidelines for Good Clinical Practice (GCP) and the principles of the “Declaration of Helsinki”, or the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual. The study complied with the requirements of the ICH E2A guideline (Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). The studies conducted in the United States under a U.S. Investigational New Drug (IND) application complied with FDA regulations and applicable local, state, and federal laws. Studies conducted in the European Union (EU)/European Economic Area complied with the EU Clinical Trial Directive (2001/20/EC).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Feb 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 1 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    France: 12
    Country: Number of subjects enrolled
    United Kingdom: 17
    Country: Number of subjects enrolled
    Poland: 9
    Country: Number of subjects enrolled
    Canada: 13
    Country: Number of subjects enrolled
    United States: 37
    Worldwide total number of subjects
    95
    EEA total number of subjects
    45
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    55
    From 65 to 84 years
    39
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 95 participants were randomized in the study. Two participants, 1 in each arm, were randomized but did not receive any study treatment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Lifastuzumab Vedotin
    Arm description
    		 Lifastuzumab vedotin was administered at a dose of 2.4 milligrams per kilogram (mg/kg) via intravenous (IV) infusion on Day 1 of each cycle (1 cycle = 21 days) until significant toxicity, disease progression, or withdrawal from the study, which corresponded to study treatment discontinuation date (overall up to approximately 2 years). After study treatment discontinuation, participants were followed on the study until withdrawal of consent, death, or lost to follow-up or study closure by the Sponsor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lifastuzumab Vedotin
    Investigational medicinal product code
    Other name
    DNIB0600A
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lifastuzumab vedotin was administered at a dose of 2.4 mg/kg via IV infusion on Day 1 of each cycle (1 cycle = 21 days).

    Arm title
    		 Pegylated Liposomal Doxorubicin (PLD)
    Arm description
    		 PLD was administered at a dose of 40 milligrams per meter-squared (mg/m^2) via IV infusion on Day 1 of each cycle (1 cycle = 28 days) until significant toxicity, disease progression, or withdrawal from the study, which corresponded to study treatment discontinuation date (overall up to approximately 2 years). After study treatment discontinuation, participants were followed on the study until withdrawal of consent, death, or lost to follow-up or study closure by the Sponsor.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doxorubicin Hydrochloride
    Investigational medicinal product code
    Other name
    PLD, Caelyx, Doxil, and Lipodox
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    PLD was administered at a dose of 40 mg/m^2 via IV infusion on Day 1 of each cycle (1 cycle = 28 days).

    Number of subjects in period 1
    		Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Started
    47
    48
    Completed
    0
    0
    Not completed
    47
    48
         Consent withdrawn by subject
    1
    3
         Death
    17
    18
         Unspecified
    1
    1
         Study Terminated by Sponsor
    28
    26

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Lifastuzumab Vedotin
    Reporting group description
    		 Lifastuzumab vedotin was administered at a dose of 2.4 milligrams per kilogram (mg/kg) via intravenous (IV) infusion on Day 1 of each cycle (1 cycle = 21 days) until significant toxicity, disease progression, or withdrawal from the study, which corresponded to study treatment discontinuation date (overall up to approximately 2 years). After study treatment discontinuation, participants were followed on the study until withdrawal of consent, death, or lost to follow-up or study closure by the Sponsor.

    Reporting group title
    Pegylated Liposomal Doxorubicin (PLD)
    Reporting group description
    		 PLD was administered at a dose of 40 milligrams per meter-squared (mg/m^2) via IV infusion on Day 1 of each cycle (1 cycle = 28 days) until significant toxicity, disease progression, or withdrawal from the study, which corresponded to study treatment discontinuation date (overall up to approximately 2 years). After study treatment discontinuation, participants were followed on the study until withdrawal of consent, death, or lost to follow-up or study closure by the Sponsor.

    Reporting group values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD) Total
    Number of subjects
    		 47 48 95
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.7 ± 9.2 62.9 ± 7.4 -
    Gender Categorical
    Units: Subjects
        Female
    		 47 48 95
        Male
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Lifastuzumab Vedotin
    Reporting group description
    		 Lifastuzumab vedotin was administered at a dose of 2.4 milligrams per kilogram (mg/kg) via intravenous (IV) infusion on Day 1 of each cycle (1 cycle = 21 days) until significant toxicity, disease progression, or withdrawal from the study, which corresponded to study treatment discontinuation date (overall up to approximately 2 years). After study treatment discontinuation, participants were followed on the study until withdrawal of consent, death, or lost to follow-up or study closure by the Sponsor.

    Reporting group title
    Pegylated Liposomal Doxorubicin (PLD)
    Reporting group description
    		 PLD was administered at a dose of 40 milligrams per meter-squared (mg/m^2) via IV infusion on Day 1 of each cycle (1 cycle = 28 days) until significant toxicity, disease progression, or withdrawal from the study, which corresponded to study treatment discontinuation date (overall up to approximately 2 years). After study treatment discontinuation, participants were followed on the study until withdrawal of consent, death, or lost to follow-up or study closure by the Sponsor.

    Primary: Percentage of Participants With Disease Progression as Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death

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    End point title
    		 Percentage of Participants With Disease Progression as Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death [1]
    End point description
    Progressive disease (PD) was defined as greater than or equal to (>/=) 20 percent (%) relative increase and >/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Unequivocal progression of existing non-TLs or appearance of 1 or more new lesions. Percentage of participants with PD event or death as assessed by investigator is reported. Analysis was performed on Intent-to-treat (ITT) population, which included all participants who were randomized to any of the study treatments.
    End point type
    Primary
    End point timeframe
    From baseline up to disease progression or death within 30 days of last study drug administration (overall up to approximately 2 years and 1 month)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups.
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    47
    48
    Units: percentage of participants
        number (not applicable)
    89.4
    81.3
    No statistical analyses for this end point

    Primary: PFS as Assessed by Investigator According to RECIST v1.1

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    End point title
    		 PFS as Assessed by Investigator According to RECIST v1.1
    End point description
    PFS was defined as the time from first intake of any study medication until the first radiographically documented progression of disease or death from any cause, whichever occurred first. Participants with no PFS events were censored at the time of the last evaluable tumor assessment. Participants with no baseline or no tumor assessment after the baseline visit were censored at the time of randomization plus 1 day. PD: >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Unequivocal progression of existing non-TLs or appearance of 1 or more new lesions. PFS was estimated using Kaplan-Meier estimates. 95% confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley. Analysis was performed on ITT population.
    End point type
    Primary
    End point timeframe
    From baseline up to disease progression or death within 30 days of last study drug administration (overall up to approximately 2 years and 1 month)
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    47
    48
    Units: months
        median (confidence interval 95%)
    5.36 (3.91 to 5.55)
    3.14 (1.87 to 5.85)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Unstratified Analysis
    Comparison groups
    Pegylated Liposomal Doxorubicin (PLD) v Lifastuzumab Vedotin
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 = 0.718
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 1.44
    Notes
    [2] - Hazard ratio was estimated by Cox regression.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Stratified Analysis: The stratification variables were platinum-free interval (less than [<] 3 months, >/=3 months), number of prior platinum-containing regimens (<2, >/=2) and number of prior therapies received in platinum-resistance setting (0, >/=1).
    Comparison groups
    Lifastuzumab Vedotin v Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.52
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.36
    Notes
    [3] - Hazard ratio was estimated by Cox regression.

    Primary: Percentage of Participants With Disease Progression as Assessed by Investigator According to RECIST v1.1 or Death in Participants With NaPi2b-High Tumors

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    End point title
    		 Percentage of Participants With Disease Progression as Assessed by Investigator According to RECIST v1.1 or Death in Participants With NaPi2b-High Tumors [4]
    End point description
    PD: >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Unequivocal progression of existing non-TLs or appearance of 1 or more new lesions. Percentage of participants with PD event or death as assessed by investigator is reported. Analysis was performed on NaPi2b-high population, which included all randomized participants with high NaPi2b expression in tumor tissues classified as immunohistochemistry (IHC) 2+/3+.
    End point type
    Primary
    End point timeframe
    From baseline up to disease progression or death within 30 days of last study drug administration (overall up to approximately 2 years and 1 month)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups.
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    42
    43
    Units: percentage of participants
        number (not applicable)
    90.5
    81.4
    No statistical analyses for this end point

    Primary: PFS as Assessed by Investigator According to RECIST v1.1 in Participants with NaPi2b-High Tumors

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    End point title
    		 PFS as Assessed by Investigator According to RECIST v1.1 in Participants with NaPi2b-High Tumors
    End point description
    PFS was defined as the time from first intake of any study medication until the first radiographically documented progression of disease or death from any cause, whichever occurred first. Participants with no PFS events were censored at the time of the last evaluable tumor assessment. Participants with no baseline or no tumor assessment after the baseline visit were censored at the time of randomization plus 1 day. PD: >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Unequivocal progression of existing non-TLs or appearance of 1 or more new lesions. PFS was estimated using Kaplan-Meier estimates. 95% CI for median was computed using the method of Brookmeyer and Crowley. Analysis was performed on NaPi2b-high population.
    End point type
    Primary
    End point timeframe
    From baseline up to disease progression or death within 30 days of last study drug administration (overall up to approximately 2 years and 1 month)
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    42
    43
    Units: months
        median (confidence interval 95%)
    5.36 (3.91 to 6.97)
    3.42 (1.87 to 5.85)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Unstratified Analysis
    Comparison groups
    Lifastuzumab Vedotin v Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.7582
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 1.48
    Notes
    [5] - Hazard ratio was estimated by Cox regression.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Stratified Analysis: The stratification variables were platinum-free interval (<3 months, >/=3 months), number of prior platinum-containing regimens (<2, >/=2) and number of prior therapies received in platinum-resistance setting (0, >/=1).
    Comparison groups
    Lifastuzumab Vedotin v Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.4536
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 1.35
    Notes
    [6] - Hazard ratio was estimated by Cox regression.

    Secondary: Percentage of Participants With Objective Response According to RECIST v1.1

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    End point title
    		 Percentage of Participants With Objective Response According to RECIST v1.1
    End point description
    Objective response was defined as percentage of participants with a confirmed complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST v1.1. CR was defined as the disappearance of all TLs and short axis (SA) reduction to <10 mm for nodal TLs/ non-TLs. PR was defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. Confirmation of response at a consecutive tumor assessment at least 4 weeks apart was required. The 95% CI was computed using Blyth-Still-Casella approach. Analysis was performed on ITT population.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days of last study drug administration (overall up to approximately 2 years and 1 month)
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    47
    48
    Units: percentage of participants
        number (confidence interval 95%)
    36.2 (22.67 to 51.48)
    16.7 (7.65 to 29.48)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lifastuzumab Vedotin v Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0309
    Method
    		 Chi-squared
    Parameter type
    		 Difference in Response Rates
    Point estimate
    19.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.19
         upper limit
    		 36.82

    Secondary: Percentage of Participants With Objective Response According to RECIST v1.1 in Participants with NaPi2b-High Tumors

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    End point title
    		 Percentage of Participants With Objective Response According to RECIST v1.1 in Participants with NaPi2b-High Tumors
    End point description
    Objective response was defined as percentage of participants with a confirmed CR or PR as assessed by the investigator according to RECIST v1.1. CR was defined as the disappearance of all TLs and SA reduction to <10 mm for nodal TLs/ non-TLs. PR was defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. Confirmation of response at a consecutive tumor assessment at least 4 weeks apart was required. The 95% CI was computed using Blyth-Still-Casella approach. Analysis was performed on NaPi2b-high population.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days of last study drug administration (overall up to approximately 2 years and 1 month)
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    42
    43
    Units: percentage of participants
        number (confidence interval 95%)
    38.1 (24.74 to 54.36)
    16.3 (7.31 to 29.47)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lifastuzumab Vedotin v Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0236
    Method
    		 Chi-squared
    Parameter type
    		 Difference in Response Rates
    Point estimate
    21.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.45
         upper limit
    		 40.19

    Secondary: Duration of Objective Response (DOR)

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    End point title
    		 Duration of Objective Response (DOR)
    End point description
    DOR was defined as the time from first documented objective response to first documented PD or death from any cause, whichever occurred earlier. Objective response was defined as percentage of participants with a confirmed CR or PR as assessed by the investigator according to RECIST v1.1. CR: disappearance of all TLs and SA reduction to <10 mm for nodal TLs/ non-TLs. PR: >/=30% decrease in SD of TLs, taking as reference the baseline SD. PD: >/=20% increase in the SD, taking as reference the smallest SD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, CR: disappearance of all non-TLs; PR: persistence of 1 or more non-TLs; and PD: appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. DOR was planned to be estimated using Kaplan-Meier estimates in ITT population. The data "99999" in results indicate that the Median was not reached due to insufficient number of participants with event.
    End point type
    Secondary
    End point timeframe
    From occurrence of a documented objective response until relapse or death from any cause (overall up to approximately 2.5 years)
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    47
    48
    Units: months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: DOR in Participants with NaPi2b-High Tumors

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    End point title
    		 DOR in Participants with NaPi2b-High Tumors
    End point description
    DOR was defined as the time from first documented objective response to first documented PD or death from any cause, whichever occurred earlier. Objective response was defined as percentage of participants with a confirmed CR or PR as assessed by the investigator according to RECIST v1.1. CR: disappearance of all TLs and SA reduction to <10 mm for nodal TLs/ non-TLs. PR: >/=30% decrease in SD of TLs, taking as reference the baseline SD. PD: >/=20% increase in the SD, taking as reference the smallest SD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, CR: disappearance of all non-TLs; PR: persistence of 1 or more non-TLs; and PD: appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. DOR was planned to be estimated using Kaplan-Meier estimates in NaPi2b-high population. The data "99999" in results indicate that the Median was not reached due to insufficient number of participants with event.
    End point type
    Secondary
    End point timeframe
    From occurrence of a documented objective response until relapse or death from any cause (overall up to approximately 2.5 years)
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    42
    43
    Units: months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Died due to any Cause

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    End point title
    		 Percentage of Participants Who Died due to any Cause
    End point description
    Percentage of Participants who died due to any cause is reported. All deaths were included, whether they occurred during the study or following treatment discontinuation. Analysis was performed on ITT population.
    End point type
    Secondary
    End point timeframe
    From baseline up to death from any cause (overall up to approximately 2.5 years)
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    47
    48
    Units: percentage of participants
        number (not applicable)
    36.2
    37.5
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time from first intake of any study medication to the date of death, regardless of the cause of death. Participants who were known to be alive at the time of the analysis were censored at the date of the last follow-up assessment. OS was estimated using Kaplan-Meier estimates. 95% CI for median was computed using the method of Brookmeyer and Crowley. Analysis was performed on ITT population. The data ‘99999’ in the results signifies that Median and Upper Limit could not be calculated due to insufficient number of participants who had an event.
    End point type
    Secondary
    End point timeframe
    From baseline up to death from any cause (overall up to approximately 2.5 years)
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    47
    48
    Units: months
        median (confidence interval 95%)
    99999 (11.992 to 99999)
    18.858 (12.55 to 99999)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Unstratified Analysis
    Comparison groups
    Lifastuzumab Vedotin v Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 = 0.9166
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.49
         upper limit
    		 1.88
    Notes
    [7] - Hazard ratio was estimated by Cox regression.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Stratified Analysis: The stratification variables were platinum-free interval (<3 months, >/=3 months), number of prior platinum-containing regimens (<2, >/=2) and number of prior therapies received in platinum-resistance setting (0, >/=1).
    Comparison groups
    Lifastuzumab Vedotin v Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 = 0.6291
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 1.71
    Notes
    [8] - Hazard ratio was estimated by Cox regression.

    Secondary: Percentage of Participants Who Died due to any Cause in Participants with NaPi2b-High Tumors

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    End point title
    		 Percentage of Participants Who Died due to any Cause in Participants with NaPi2b-High Tumors
    End point description
    Percentage of Participants who died due to any cause is reported. All deaths were included, whether they occurred during the study or following treatment discontinuation. Analysis was performed on NaPi2b-high population.
    End point type
    Secondary
    End point timeframe
    From baseline up to death from any cause (overall up to approximately 2.5 years)
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    42
    43
    Units: percentage of participants
        number (not applicable)
    33.3
    39.5
    No statistical analyses for this end point

    Secondary: OS in Participants with NaPi2b-High Tumors

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    End point title
    		 OS in Participants with NaPi2b-High Tumors
    End point description
    OS was defined as the time from first intake of any study medication to the date of death, regardless of the cause of death. Participants who were known to be alive at the time of the analysis were censored at the date of the last follow-up assessment. OS was estimated using Kaplan-Meier estimates. 95% CI for median was computed using the method of Brookmeyer and Crowley. Analysis was performed on NaPi2b-high population. The data ‘99999’ in the results signifies that Median and Upper Limit could not be calculated due to insufficient number of participants who had an event.
    End point type
    Secondary
    End point timeframe
    From baseline up to death from any cause (overall up to approximately 2.5 years)
    End point values
    		 Lifastuzumab Vedotin Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects analysed
    42
    43
    Units: months
        median (confidence interval 95%)
    99999 (11.992 to 99999)
    18.858 (12.386 to 99999)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Unstratified Analysis
    Comparison groups
    Lifastuzumab Vedotin v Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0.6743
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 1.75
    Notes
    [9] - Hazard ratio was estimated by Cox regression.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Stratified Analysis: The stratification variables were platinum-free interval (<3 months, >/=3 months), number of prior platinum-containing regimens (<2, >/=2) and number of prior therapies received in platinum-resistance setting (0, >/=1).
    Comparison groups
    Lifastuzumab Vedotin v Pegylated Liposomal Doxorubicin (PLD)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    P-value
    		 = 0.2509
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3
         upper limit
    		 1.38
    Notes
    [10] - Hazard ratio was estimated by Cox regression.

    Secondary: Area Under the Serum Concentration-time Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Lifastuzumab Vedotin Total Antibody

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    End point title
    		 Area Under the Serum Concentration-time Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Lifastuzumab Vedotin Total Antibody [11]
    End point description
    AUC0-inf indicates the serum concentration of the total antibody (conjugated and unconjugated antibody) over time. Analysis was performed on pharmacokinetic (PK)-evaluable population, which included all participants who received any amount of study drug and who had any available PK data. Here 'Number of Subject Analysed' indicates number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0), 30 minutes post-infusion (infusion length=90 minutes) on Day 1 of Cycle 1 (1 cycle=21 days); Day 8 of Cycle 1; Day 15 of Cycle 1
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK analyses were carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    22
    Units: day*microgram/milliliter (day*mcg/mL)
        arithmetic mean (standard deviation)
    234.85 ± 50.75
    No statistical analyses for this end point

    Secondary: AUC0-inf of Lifastuzumab Vedotin Antibody-Conjugated Monomethyl Auristatin E (acMMAE)

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    End point title
    		 AUC0-inf of Lifastuzumab Vedotin Antibody-Conjugated Monomethyl Auristatin E (acMMAE) [12]
    End point description
    AUC0-inf indicated the plasma concentration of the acMMAE over time. Analysis was performed on PK-evaluable population. Here 'Number of Subject Analysed' indicates number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0), 30 minutes post-infusion (infusion length=90 minutes) on Day 1 of Cycle 1 (1 cycle=21 days); Day 8 of Cycle 1; Day 15 of Cycle 1
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK analyses were carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    23
    Units: day*nanogram (ng)/mL
        arithmetic mean (standard deviation)
    2549.53 ± 566.86
    No statistical analyses for this end point

    Secondary: Maximum Serum Concentration (Cmax) of Lifastuzumab Vedotin Total Antibody

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    End point title
    		 Maximum Serum Concentration (Cmax) of Lifastuzumab Vedotin Total Antibody [13]
    End point description
    Cmax is the maximum total antibody serum concentration observed during dosing period. Analysis was performed on PK-evaluable population. Here 'Number of Subject Analysed' indicates number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0), 30 minutes post infusion (infusion length=90 minutes) on Day 1 of Cycle 1 (1 cycle=21 days); Day 8 of Cycle 1; Day 15 of Cycle 1
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK analyses were carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    33
    Units: mcg/mL
        arithmetic mean (standard deviation)
    41.97 ± 14.81
    No statistical analyses for this end point

    Secondary: Cmax of Lifastuzumab Vedotin acMMAE

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    End point title
    		 Cmax of Lifastuzumab Vedotin acMMAE [14]
    End point description
    Cmax is the maximum acMMAE plasma concentration observed during dosing period. Analysis was performed on PK-evaluable population. Here 'Number of Subject Analysed' indicates number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0), 30 minutes post infusion (infusion length=90 minutes) on Day 1 of Cycle 1 (1 cycle=21 days); Day 8 of Cycle 1; Day 15 of Cycle 1
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK analyses were carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    33
    Units: ng/mL
        arithmetic mean (standard deviation)
    748.89 ± 274.22
    No statistical analyses for this end point

    Secondary: Cmax of Unconjugated Monomethyl Auristatin E (MMAE)

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    End point title
    		 Cmax of Unconjugated Monomethyl Auristatin E (MMAE) [15]
    End point description
    Cmax is the maximum unconjugated MMAE plasma concentration observed during dosing period. Analysis was performed on PK-evaluable population. Here 'Number of Subject Analysed' indicates number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0), 30 minutes post infusion (infusion length=90 minutes) on Day 1 of Cycle 1 (1 cycle=21 days); Day 8 of Cycle 1; Day 15 of Cycle 1
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK analyses were carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    33
    Units: ng/mL
        arithmetic mean (standard deviation)
    2.78 ± 2.47
    No statistical analyses for this end point

    Secondary: Clearance (CL) of Lifastuzumab Vedotin Total Antibody

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    End point title
    		 Clearance (CL) of Lifastuzumab Vedotin Total Antibody [16]
    End point description
    CL is a quantitative measure of the rate at which total antibody is removed from the body. Analysis was performed on PK-evaluable population. Here 'Number of Subject Analysed' indicates number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0), 30 minutes post infusion (infusion length=90 minutes) on Day 1 of Cycle 1 (1 cycle=21 days); Day 8 of Cycle 1; Day 15 of Cycle 1
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK analyses were carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    22
    Units: mL/day/kilogram (kg)
        arithmetic mean (standard deviation)
    10.75 ± 2.62
    No statistical analyses for this end point

    Secondary: CL of Lifastuzumab Vedotin acMMAE

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    End point title
    		 CL of Lifastuzumab Vedotin acMMAE [17]
    End point description
    CL is a quantitative measure of the rate at which acMMAE is removed from the body. Analysis was performed on PK-evaluable population. Here 'Number of Subject Analysed' indicates number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0), 30 minutes post infusion (infusion length=90 minutes) on Day 1 of Cycle 1 (1 cycle=21 days); Day 8 of Cycle 1; Day 15 of Cycle 1
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK analyses were carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    23
    Units: mL/day/kg
        arithmetic mean (standard deviation)
    16.95 ± 3.57
    No statistical analyses for this end point

    Secondary: Elimination Half-life (t1/2) of Lifastuzumab Vedotin Total Antibody

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    End point title
    		 Elimination Half-life (t1/2) of Lifastuzumab Vedotin Total Antibody [18]
    End point description
    Elimination half-life is the time measured for the total antibody serum concentration to decrease by one half. Analysis was performed on PK-evaluable population. Here 'Number of Subject Analysed' indicates number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0), 30 minutes post infusion (infusion length=90 minutes) on Day 1 of Cycle 1 (1 cycle=21 days); Day 8 of Cycle 1; Day 15 of Cycle 1
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK analyses were carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    22
    Units: days
        median (full range (min-max))
    6.28 (3.2 to 10.9)
    No statistical analyses for this end point

    Secondary: t1/2 of Lifastuzumab Vedotin acMMAE

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    End point title
    		 t1/2 of Lifastuzumab Vedotin acMMAE [19]
    End point description
    Elimination half-life is the time measured for the acMMAE plasma concentration to decrease by one half. Analysis was performed on PK-evaluable population. Here 'Number of Subject Analysed' indicates number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0), 30 minutes post infusion (infusion length=90 minutes) on Day 1 of Cycle 1 (1 cycle=21 days); Day 8 of Cycle 1; Day 15 of Cycle 1
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK analyses were carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    23
    Units: days
        median (full range (min-max))
    4.78 (3.1 to 9.2)
    No statistical analyses for this end point

    Secondary: Volume of Distribution at Steady State (Vss) of Lifastuzumab Vedotin Total Antibody

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    End point title
    		 Volume of Distribution at Steady State (Vss) of Lifastuzumab Vedotin Total Antibody [20]
    End point description
    Volume of distribution is defined as the theoretical volume in which the total antibody would need to be uniformly distributed to produce the desired serum concentration. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Analysis was performed on PK-evaluable population. Here 'Number of Subject Analysed' indicates number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0), 30 minutes post infusion (infusion length=90 minutes) on Day 1 of each Cycle (1 cycle=21 days) (overall up to approximately 2 years); Day 8 of Cycle 1; Day 15 of Cycles 1-4
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK analyses were carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    22
    Units: mL/kg
        arithmetic mean (standard deviation)
    77.27 ± 21.55
    No statistical analyses for this end point

    Secondary: Vss of Lifastuzumab Vedotin acMMAE

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    End point title
    		 Vss of Lifastuzumab Vedotin acMMAE [21]
    End point description
    Volume of distribution is defined as the theoretical volume in which the acMMAE would need to be uniformly distributed to produce the desired plasma concentration. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Analysis was performed on PK-evaluable population. Here 'Number of Subject Analysed' indicates number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0), 30 minutes post infusion (infusion length=90 minutes) on Day 1 of each Cycle (1 cycle=21 days) (overall up to approximately 2 years); Day 8 of Cycle 1; Day 15 of Cycles 1-4
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK analyses were carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    23
    Units: mL/kg
        arithmetic mean (standard deviation)
    72.21 ± 19.34
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Lifastuzumab Vedotin

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    End point title
    		 Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Lifastuzumab Vedotin [22]
    End point description
    Percentage of participants with positive ATA results was reported. Analysis was performed on immunogenicity-evaluable population, which included all participants who received any amount of study drug and who had any available ATA data. Here 'n' indicates number of participants evaluable at indicated time points.
    End point type
    Secondary
    End point timeframe
    Baseline (Pre-infusion [Hour 0] on Day 1 of Cycle 1); Post-baseline (Pre-infusion [Hour 0] on Day 1 of Cycles 2-4, at approximately 15-30 days after last infusion administration [maximum up to approximately 2 years]) (1 cycle=21 days)
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: ATA analysis was carried out only in the Lifastuzumab Vedotin arm (PLD arm was excluded).
    End point values
    		 Lifastuzumab Vedotin
    Number of subjects analysed
    46
    Units: percentage of participants
    number (not applicable)
        Baseline (n=46)
    6.5
        Post-baseline (n=44)
    34.1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline up to 30 days of last study drug administration (overall up to approximately 2 years and 1 month)
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Lifastuzumab Vedotin (DNIB0600A)
    Reporting group description
    		 DNIB0600A was administered at a dose of 2.4 milligrams per kilogram (mg/kg) via intravenous (IV) infusion on Day 1 of each cycle (1 cycle = 21 days) until significant toxicity, disease progression, or withdrawal from the study, which corresponded to study treatment discontinuation date (overall up to approximately 2 years). After study treatment discontinuation, participants were followed on the study until withdrawal of consent, death, or lost to follow-up or study closure by the Sponsor.

    Reporting group title
    Pegylated Liposomal Doxorubicin (PLD)
    Reporting group description
    		 PLD was administered at a dose of 40 milligrams per meter-squared (mg/m^2) via IV infusion on Day 1 of each cycle (1 cycle = 28 days) until significant toxicity, disease progression, or withdrawal from the study, which corresponded to study treatment discontinuation date (overall up to approximately 2 years). After study treatment discontinuation, participants were followed on the study until withdrawal of consent, death, or lost to follow-up or study closure by the Sponsor.

    Serious adverse events
    		 Lifastuzumab Vedotin (DNIB0600A) Pegylated Liposomal Doxorubicin (PLD)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    15 / 47 (31.91%)
    16 / 48 (33.33%)
         number of deaths (all causes)
    17
    18
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma gastric
         subjects affected / exposed
    0 / 47 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Spinal fracture
         subjects affected / exposed
    0 / 47 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 47 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 47 (0.00%)
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    3 / 47 (6.38%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 47 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Dry eye
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    4 / 47 (8.51%)
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal tenderness
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall haematoma
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 47 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 47 (2.13%)
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 47 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 47 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 47 (2.13%)
    3 / 48 (6.25%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 47 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 47 (0.00%)
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 47 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 47 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 47 (2.13%)
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Lifastuzumab Vedotin (DNIB0600A) Pegylated Liposomal Doxorubicin (PLD)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    46 / 47 (97.87%)
    45 / 48 (93.75%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 47 (12.77%)
    6 / 48 (12.50%)
         occurrences all number
    7
    10
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    8 / 47 (17.02%)
    7 / 48 (14.58%)
         occurrences all number
    26
    7
    Chest discomfort
         subjects affected / exposed
    0 / 47 (0.00%)
    7 / 48 (14.58%)
         occurrences all number
    0
    7
    Chills
         subjects affected / exposed
    1 / 47 (2.13%)
    3 / 48 (6.25%)
         occurrences all number
    1
    3
    Fatigue
         subjects affected / exposed
    21 / 47 (44.68%)
    27 / 48 (56.25%)
         occurrences all number
    33
    43
    Mucosal inflammation
         subjects affected / exposed
    2 / 47 (4.26%)
    6 / 48 (12.50%)
         occurrences all number
    2
    8
    Oedema peripheral
         subjects affected / exposed
    3 / 47 (6.38%)
    5 / 48 (10.42%)
         occurrences all number
    3
    10
    Pyrexia
         subjects affected / exposed
    8 / 47 (17.02%)
    6 / 48 (12.50%)
         occurrences all number
    10
    8
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    4 / 47 (8.51%)
    0 / 48 (0.00%)
         occurrences all number
    4
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 47 (4.26%)
    8 / 48 (16.67%)
         occurrences all number
    2
    11
    Dyspnoea
         subjects affected / exposed
    6 / 47 (12.77%)
    9 / 48 (18.75%)
         occurrences all number
    9
    10
    Oropharyngeal pain
         subjects affected / exposed
    2 / 47 (4.26%)
    4 / 48 (8.33%)
         occurrences all number
    2
    5
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 47 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    0
    3
    Insomnia
         subjects affected / exposed
    4 / 47 (8.51%)
    5 / 48 (10.42%)
         occurrences all number
    4
    5
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    7 / 47 (14.89%)
    3 / 48 (6.25%)
         occurrences all number
    11
    5
    Aspartate aminotransferase increased
         subjects affected / exposed
    5 / 47 (10.64%)
    2 / 48 (4.17%)
         occurrences all number
    15
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 47 (2.13%)
    3 / 48 (6.25%)
         occurrences all number
    1
    3
    Neutrophil count decreased
         subjects affected / exposed
    1 / 47 (2.13%)
    3 / 48 (6.25%)
         occurrences all number
    2
    6
    Weight decreased
         subjects affected / exposed
    2 / 47 (4.26%)
    5 / 48 (10.42%)
         occurrences all number
    3
    5
    White blood cell count decreased
         subjects affected / exposed
    0 / 47 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    0
    9
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 47 (4.26%)
    5 / 48 (10.42%)
         occurrences all number
    2
    5
    Dysgeusia
         subjects affected / exposed
    3 / 47 (6.38%)
    5 / 48 (10.42%)
         occurrences all number
    3
    6
    Headache
         subjects affected / exposed
    9 / 47 (19.15%)
    7 / 48 (14.58%)
         occurrences all number
    9
    9
    Neuropathy peripheral
         subjects affected / exposed
    3 / 47 (6.38%)
    0 / 48 (0.00%)
         occurrences all number
    3
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    8 / 47 (17.02%)
    3 / 48 (6.25%)
         occurrences all number
    17
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    10 / 47 (21.28%)
    8 / 48 (16.67%)
         occurrences all number
    14
    9
    Leukopenia
         subjects affected / exposed
    1 / 47 (2.13%)
    3 / 48 (6.25%)
         occurrences all number
    1
    4
    Neutropenia
         subjects affected / exposed
    14 / 47 (29.79%)
    8 / 48 (16.67%)
         occurrences all number
    27
    28
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 47 (2.13%)
    3 / 48 (6.25%)
         occurrences all number
    1
    3
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    4 / 47 (8.51%)
    1 / 48 (2.08%)
         occurrences all number
    5
    1
    Abdominal distension
         subjects affected / exposed
    3 / 47 (6.38%)
    3 / 48 (6.25%)
         occurrences all number
    3
    4
    Abdominal pain
         subjects affected / exposed
    19 / 47 (40.43%)
    11 / 48 (22.92%)
         occurrences all number
    35
    16
    Abdominal pain upper
         subjects affected / exposed
    4 / 47 (8.51%)
    4 / 48 (8.33%)
         occurrences all number
    5
    4
    Ascites
         subjects affected / exposed
    2 / 47 (4.26%)
    3 / 48 (6.25%)
         occurrences all number
    2
    5
    Constipation
         subjects affected / exposed
    12 / 47 (25.53%)
    18 / 48 (37.50%)
         occurrences all number
    17
    23
    Diarrhoea
         subjects affected / exposed
    18 / 47 (38.30%)
    9 / 48 (18.75%)
         occurrences all number
    26
    10
    Dyspepsia
         subjects affected / exposed
    1 / 47 (2.13%)
    5 / 48 (10.42%)
         occurrences all number
    1
    10
    Flatulence
         subjects affected / exposed
    0 / 47 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    0
    3
    Gastrooesophageal reflux disease
         subjects affected / exposed
    4 / 47 (8.51%)
    0 / 48 (0.00%)
         occurrences all number
    4
    0
    Nausea
         subjects affected / exposed
    21 / 47 (44.68%)
    22 / 48 (45.83%)
         occurrences all number
    38
    27
    Stomatitis
         subjects affected / exposed
    3 / 47 (6.38%)
    15 / 48 (31.25%)
         occurrences all number
    4
    25
    Vomiting
         subjects affected / exposed
    13 / 47 (27.66%)
    12 / 48 (25.00%)
         occurrences all number
    21
    16
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    3 / 47 (6.38%)
    0 / 48 (0.00%)
         occurrences all number
    11
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    6 / 47 (12.77%)
    4 / 48 (8.33%)
         occurrences all number
    7
    4
    Erythema
         subjects affected / exposed
    2 / 47 (4.26%)
    3 / 48 (6.25%)
         occurrences all number
    2
    3
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 47 (0.00%)
    12 / 48 (25.00%)
         occurrences all number
    0
    17
    Pruritus
         subjects affected / exposed
    0 / 47 (0.00%)
    4 / 48 (8.33%)
         occurrences all number
    0
    5
    Rash
         subjects affected / exposed
    2 / 47 (4.26%)
    4 / 48 (8.33%)
         occurrences all number
    2
    7
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 47 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    0
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 47 (8.51%)
    4 / 48 (8.33%)
         occurrences all number
    4
    4
    Back pain
         subjects affected / exposed
    5 / 47 (10.64%)
    7 / 48 (14.58%)
         occurrences all number
    5
    9
    Groin pain
         subjects affected / exposed
    0 / 47 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    0
    4
    Muscle spasms
         subjects affected / exposed
    4 / 47 (8.51%)
    2 / 48 (4.17%)
         occurrences all number
    4
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 47 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    0
    5
    Myalgia
         subjects affected / exposed
    5 / 47 (10.64%)
    2 / 48 (4.17%)
         occurrences all number
    6
    2
    Pain in extremity
         subjects affected / exposed
    4 / 47 (8.51%)
    1 / 48 (2.08%)
         occurrences all number
    4
    4
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    3 / 47 (6.38%)
    1 / 48 (2.08%)
         occurrences all number
    3
    2
    Sinusitis
         subjects affected / exposed
    3 / 47 (6.38%)
    1 / 48 (2.08%)
         occurrences all number
    3
    1
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 47 (4.26%)
    5 / 48 (10.42%)
         occurrences all number
    2
    5
    Urinary tract infection
         subjects affected / exposed
    8 / 47 (17.02%)
    9 / 48 (18.75%)
         occurrences all number
    8
    10
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    19 / 47 (40.43%)
    16 / 48 (33.33%)
         occurrences all number
    23
    18
    Dehydration
         subjects affected / exposed
    3 / 47 (6.38%)
    2 / 48 (4.17%)
         occurrences all number
    4
    2
    Hyperglycaemia
         subjects affected / exposed
    4 / 47 (8.51%)
    2 / 48 (4.17%)
         occurrences all number
    5
    5
    Hypokalaemia
         subjects affected / exposed
    4 / 47 (8.51%)
    3 / 48 (6.25%)
         occurrences all number
    6
    5
    Hypomagnesaemia
         subjects affected / exposed
    5 / 47 (10.64%)
    8 / 48 (16.67%)
         occurrences all number
    7
    13

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Feb 2014
    Protocol was amended to include the following changes: Clinical data on lifastuzumab vedotin was updated as of 18 September 2013; An inclusion criterion was added specifying that participants must have at least one lesion that is measurable per RECIST v1.1 criteria; The inclusion criteria was modified to allow enrollment of participants who had received no more than one prior cytotoxic chemotherapy regimen for the treatment of PROC and no more than two total regimens; Due to the global shortage of PLD ongoing at the time of amendment, it was clarified that the Sponsor will supply PLD to U.S. sites in cases where they were unable to obtain or were relying on their own local supply; For participants who had a change in bodyweight of +/- 10%, allowance was made for dose adjustment of PLD after discussion with the medical monitor; Allowance was made for dose modifications for PLD to be made in accordance with local institutional standards; Information on cardiotoxicity and PLD dose modification was added; The study treatment designation for PLD was changed from the “standard of care non-investigational drug” to an “investigational study drug” because it was administered at a lower dose than what was indicated on the approved drug label; The timing of pregnancy testing for women of childbearing potential was modified; Additional electrocardiogram (ECG) monitoring was added in the PLD arm due to cardiac toxicity being a known risk for the drug; A clarification was added that the timing of the first electronic patient-reported outcome (ePRO) collection was on Cycle 1, Day 1 but prior to the participant being informed of their study drug assignment; The schedule of assessments in the protocol was corrected.
    17 Mar 2014
    Language regarding study drug discontinuation in participants who developed increases in QT intervals was modified.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Sponsor discontinued the survival follow-up in January 2016 and terminated the study in July 2016, because the primary objective of PFS did not meet pre-specified criteria.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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