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    Clinical Trial Results:
    SHERBOC: A Double-blind, Placebo-controlled, Phase 2 trial of Seribantumab Plus Fulvestrant in Postmenopausal Women with Hormone Receptor-positive, Heregulin Positive (HRG+), HER2 Negative Metastatic Breast Cancer Whose Disease Progressed After Prior Systemic Therapy

    Summary
    EudraCT number
    		 2017-000565-76
    Trial protocol
    		 DE   ES   AT   BE   IT  
    Global end of trial date
    30 Nov 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Sep 2021
    First version publication date
    01 Sep 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MM-121-02-02-10
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03241810
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merrimack Pharmaceuticals Inc.
    Sponsor organisation address
    One Kendall Square, Cambridge, United States, MA 02139
    Public contact
    Regulatory Affairs, Merrimack Pharmaceuticals Inc., 001 6174417624, GenClin-Alert@merrimack.com
    Scientific contact
    Regulatory Affairs, Merrimack Pharmaceuticals Inc., 001 6174417624, GenClin-Alert@merrimack.com
    Sponsor organisation name
    Elevation Oncology
    Sponsor organisation address
    888 7th Ave., 12th Floor, New York, United States, 10106
    Public contact
    Valerie M. Jansen, MD, PhD, Elevation Oncology, 001 716 371 1125,
    Scientific contact
    Valerie M. Jansen, MD, PhD, Elevation Oncology, 001 716 371 1125,
    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
    30 Nov 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Nov 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Nov 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to determine whether the combination of seribantumab + fulvestrant is more effective than placebo + fulvestrant based on investigator assessed Progression Free Survival (PFS) in HRG positive patients (defined as HRG ISH score of > or = to 1+)
    Protection of trial subjects
    N/A
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Aug 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 7
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    United States: 11
    Country: Number of subjects enrolled
    Canada: 1
    Worldwide total number of subjects
    22
    EEA total number of subjects
    10
    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)
    15
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 At the time of the study termination by the prior Sponsor (Merrimack Pharmaceuticals), 62 sites participated in the study (27 in North America and 36 in Europe).

    Pre-assignment
    Screening details
    		 Patients that have signed informed consent, identified as HRG positive based on centralized tissue analysis & have successfully completed study entry criteria (safety population-patients receiving at least one dose of study medication).

    Pre-assignment period milestones
    Number of subjects started
    		 22
    Number of subjects completed
    		 22

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Carer, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm A (Experimental): Seribantumab and Fulvestrant
    Arm description
    		 Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
    Arm type
    		 Experimental

    Investigational medicinal product name
    Seribantumab
    Investigational medicinal product code
    Other name
    MM-121
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle

    Investigational medicinal product name
    Fulvestrant
    Investigational medicinal product code
    Other name
    Faslodex
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle

    Arm title
    		 Arm B (Control): Placebo and Fulvestrant
    Arm description
    		 Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
    Arm type
    		 Placebo and Fulvestrant

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Solution containing 20 mM histidine, 150 mM sodium chloride, at a pH of 6.5
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenously (IV) on day 1 and 15 of each 28-day cycle

    Investigational medicinal product name
    Fulvestrant
    Investigational medicinal product code
    Other name
    Faslodex
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle

    Number of subjects in period 1
    		Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Started
    11
    11
    Completed
    11
    11

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A (Experimental): Seribantumab and Fulvestrant
    Reporting group description
    		 Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle

    Reporting group title
    Arm B (Control): Placebo and Fulvestrant
    Reporting group description
    		 Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle

    Reporting group values
    		 Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant Total
    Number of subjects
    		 11 11 22
    Age categorical
    Units: Subjects
        <=18 years
    		 0 0 0
        Between 18 and 65 years
    		 8 7 15
        >=65 years
    		 3 4 7
    Gender categorical
    Units: Subjects
        Female
    		 11 11 22
        Male
    		 0 0 0
    Metastatic burden
    Based upon the population treated, the most important baseline measure was CT scans to determine metastatic burden, as the primary endpoint was investigator assessed PFS. TNM Staging (Tumor size): T1 (T1a,T1b & T1c): 2 cm (3/4 of an inch) or less across. T2: > 2 cm but not more than 5 cm (2 inches) across. T3: > 5 cm across. T4 (T4a,T4b,T4c,T4d): Tumor of any size growing into the chest wall or skin. As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means cancer has spread more. And within a stage, an earlier letter means a lower stage.
    Units: Subjects
        TNM Stage I
    		 0 1 1
        TNM Stage II
    		 0 2 2
        TNM Stage IIa
    		 4 0 4
        TNM Stage IIb
    		 1 0 1
        TNM Stage III
    		 0 2 2
        TNM Stage IIIa
    		 1 0 1
        TNM Stage IIIc
    		 1 0 1
        TNM Stage IV
    		 4 6 10
    Heregulin positive status and staining in archival tissue
    Measure Description: Women had to be ≥ HRG 1+ positive in their submitted tumor sample to qualify for the study
    Units: Subjects
        Heregulin positive status and staining in archival
    		 11 11 22
    Subject analysis sets

    Subject analysis set title
    Intent to Treat
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Intent to treat (ITT) population treated up to 150 days

    Subject analysis set title
    Safety analysis
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety population includes patients receiving at least one dose of study medication. All safety analyses were to be performed on this population.

    Subject analysis sets values
    		 Intent to Treat Safety analysis
    Number of subjects
    22
    22
    Age categorical
    Units: Subjects
        <=18 years
        Between 18 and 65 years
        >=65 years
    Age continuous
    Units:
        
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    22
    22
        Male
    0
    0
    Metastatic burden
    Based upon the population treated, the most important baseline measure was CT scans to determine metastatic burden, as the primary endpoint was investigator assessed PFS. TNM Staging (Tumor size): T1 (T1a,T1b & T1c): 2 cm (3/4 of an inch) or less across. T2: > 2 cm but not more than 5 cm (2 inches) across. T3: > 5 cm across. T4 (T4a,T4b,T4c,T4d): Tumor of any size growing into the chest wall or skin. As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means cancer has spread more. And within a stage, an earlier letter means a lower stage.
    Units: Subjects
        TNM Stage I
    1
    1
        TNM Stage II
    2
    2
        TNM Stage IIa
    4
    4
        TNM Stage IIb
    1
    1
        TNM Stage III
    2
    2
        TNM Stage IIIa
    1
    1
        TNM Stage IIIc
    1
    1
        TNM Stage IV
    10
    10
    Heregulin positive status and staining in archival tissue
    Measure Description: Women had to be ≥ HRG 1+ positive in their submitted tumor sample to qualify for the study
    Units: Subjects
        Heregulin positive status and staining in archival
    22
    22

    End points

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    End points reporting groups
    Reporting group title
    Arm A (Experimental): Seribantumab and Fulvestrant
    Reporting group description
    		 Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle

    Reporting group title
    Arm B (Control): Placebo and Fulvestrant
    Reporting group description
    		 Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle

    Subject analysis set title
    Intent to Treat
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Intent to treat (ITT) population treated up to 150 days

    Subject analysis set title
    Safety analysis
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety population includes patients receiving at least one dose of study medication. All safety analyses were to be performed on this population.

    Primary: Progression Free Survival

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    End point title
    		 Progression Free Survival [1]
    End point description
    Progression Free Survival is defined as the time from randomization to the first documented radiographical progression of disease using RECIST v.1.1 of death from any cause, whichever comes first as assessed by the investigator. The tumor assessment (i.e., scan dates) was used for progression/censor date not the date corresponding to the determination of overall response. Progression-free survival time distribution and median survival for each treatment group were analysed using the Kaplan-Meier method.
    End point type
    Primary
    End point timeframe
    Randomization until progression of disease of death due to any cause up to 13 months (the study terminated prematurely). The primary analysis was planned to be initiated when 58 PFS events have occurred
    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: Because of the small sample size at the time of the premature study closure, only partial data are summarized in the final tables and listings, and a full clinical study report will not be written. There were no efficacy, pharmacokinetic, or biomarker data feasible for the analysis, and as such, no related analyses were performed.
    End point values
    		 Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Number of subjects analysed
    11
    11
    Units: participants
        number (not applicable)
    1
    1
    No statistical analyses for this end point

    Secondary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause. The study was terminated on 30 Nov 2018. Data represented outcomes up to 150 days of treatment.
    End point type
    Secondary
    End point timeframe
    Randomization until death due to any cause up to 13 months (the study terminated prematurely)
    End point values
    		 Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Number of subjects analysed
    11
    11
    Units: participants
        number (not applicable)
    1
    1
    No statistical analyses for this end point

    Secondary: Objective Response Rate

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    End point title
    		 Objective Response Rate
    End point description
    Objective Response Rate (ORR) is defined as the proportion of patients with a RECIST v1.1 response recorded from randomization until disease progression characterized as either a Complete Response (CR) or Partial Response (PR) relative to the total number of evaluable patients.
    End point type
    Secondary
    End point timeframe
    Randomization through end of study up to 13 months (the study terminated prematurely)
    End point values
    		 Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant Intent to Treat
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    Units: participants
    number (not applicable)
        Overall Number of Participants Analysed
    Notes
    [2] - All patients analysed had progressive disease. Therefore, they did not meet the criteria for ORR.
    [3] - All patients analysed had progressive disease. Therefore, they did not meet the criteria for ORR
    [4] - All patients analysed had progressive disease. Therefore, they did not meet the criteria for ORR
    No statistical analyses for this end point

    Secondary: Time to Progression

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    End point title
    		 Time to Progression
    End point description
    Time to Progression (TTP) is defined as the time from the date of randomization to the date of objective tumor progression.
    End point type
    Secondary
    End point timeframe
    Randomization to date of objective tumor progression up to 13 months (the study terminated prematurely)
    End point values
    		 Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Number of subjects analysed
    11
    11
    Units: Days
    median (inter-quartile range (Q1-Q3))
        Time to progression
    52 (33.25 to 72.25)
    48 (34.50 to 58.50)
    No statistical analyses for this end point

    Secondary: Number of Participant With Treatment-emergent Adverse Events Reported with the combinations of Seribantumab Plus Fulvestrant versus Fulvestrant Alone

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    End point title
    		 Number of Participant With Treatment-emergent Adverse Events Reported with the combinations of Seribantumab Plus Fulvestrant versus Fulvestrant Alone
    End point description
    Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration.
    End point type
    Secondary
    End point timeframe
    TEAEs were collected through the study completion (30Nov2018), up to 13 months. Frequency and percent summaries were presented for TEAE defined as adverse events that occurs or worsen in severity following the first dose of seribantumab, or fulvestrant.
    End point values
    		 Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant Safety analysis
    Number of subjects analysed
    11
    11
    22
    Units: Participants
        Patients with any TEAE- Related
    7
    4
    11
        Patients with any TEAE-Serious Adverse event
    1
    0
    1
        NCI-CTCAE Grade 3 or Higher
    2
    1
    3
    No statistical analyses for this end point

    Secondary: Percentage of Treatment-emergent Adverse Events Reported with the Combination of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone

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    End point title
    		 Percentage of Treatment-emergent Adverse Events Reported with the Combination of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone
    End point description
    Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration.
    End point type
    Secondary
    End point timeframe
    TEAEs were collected through the study completion (30 Nov 2018), up to 13 months. Frequency and percent summaries were presented for TEAE defined as adverse events that occur or worsen in severity following the first dose of seribantumab, or fulvestrant.
    End point values
    		 Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Number of subjects analysed
    11
    11
    Units: percent
    number (not applicable)
        TEAE-related
    63.6
    36.4
        TEAE-Serious Adverse event
    9.1
    0
        NCI-CTCAE Grade 3 or Higher
    18.2
    9.1
    No statistical analyses for this end point

    Secondary: Pharmacokinetic (PK) Profile of Seribantumab When Given in Combination With Furlvestrant and of Fulvestrant When Given in Combination With Seribantumab

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    End point title
    		 Pharmacokinetic (PK) Profile of Seribantumab When Given in Combination With Furlvestrant and of Fulvestrant When Given in Combination With Seribantumab
    End point description
    Pharmacokinetic (PK) evaluation are performed on samples obtained pre-dose on day 1 and 15 of each 28-day cycle to assess pre-treatment trough concentration of MM-121. The maximum observed concentration (Cmax) is presented and calculated using Non compartmental analysis (NCA) . Serum levels of MM-121 are measured at a central lab using an enzyme-linked immunosorbent assay (ELISA).
    End point type
    Secondary
    End point timeframe
    The study terminated prematurely after 13 months. Were to be analysed post-dose on Cycle 1, Week 1 & pre-dose for all subsequent seribantumab infusion until the completion of Cycle 2. Fulvestrant PK sample were to be collected prior to seribantumab dose.
    End point values
    		 Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant Intent to Treat
    Number of subjects analysed
    0 [5]
    0 [6]
    0 [7]
    Units: participants
        number (not applicable)
    Notes
    [5] - There was no PK data feasible for the analysis, and as such, no related analyses were performed
    [6] - There was no PK data feasible for the analysis, and as such, no related analyses were performed
    [7] - No data displayed because Outcome Measure has zero total analyzed.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline through to premature study completion up to 13 months (30 Nov 2018).
    Adverse event reporting additional description
    The safety population includes patients receiving at least one dose of study medication. All safety analyses were be performed on this population. Safety analyses (AE and laboratory analyses) were performed using the safety population. AE were coded using the latest MedDRA dictionary 21.0. Severity of AE was grade according to the NCI CTCAE v.4.03.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Arm A (Experimental): Seribantumab and Fulvestrant
    Reporting group description
    		 Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle

    Reporting group title
    Arm B (Control): Placebo and Fulvestrant
    Reporting group description
    		 Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle

    Serious adverse events
    		 Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 11 (90.91%)
    8 / 11 (72.73%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    Jugular vein thrombosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 11 (27.27%)
    1 / 11 (9.09%)
         occurrences all number
    3
    1
    Fatigue
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Chest discomfort
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Influenza like likeness
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Injection site pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Injection site reaction
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Malaise
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Vulvovaginal pruritus
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Cough
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    Epistaxis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Nasal dryness
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Pleural effusion
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Irritability
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Blood bilirubin increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    White blood cell count decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Headache
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    Hypoaesthesia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    Paraesthesia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Dry eye
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Eye allergy
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Lacrimation increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Vision blurred
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    7 / 11 (63.64%)
    3 / 11 (27.27%)
         occurrences all number
    7
    3
    Nausea
         subjects affected / exposed
    2 / 11 (18.18%)
    3 / 11 (27.27%)
         occurrences all number
    2
    3
    Dyspepsia
         subjects affected / exposed
    3 / 11 (27.27%)
    0 / 11 (0.00%)
         occurrences all number
    3
    0
    Oral pain
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Abdominal pain
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    2
    Stomatitis
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    Constipation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Dry mouth
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Dysphagia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Faeces soft
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Odynophagia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Salivary hypersecretion
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Hepatobiliary disorders
    Hepatomegaly
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    Alopecia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Dry skin
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Pain of skin
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Rash maculo-papular
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    Urine odour abnormal
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Back pain
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    Bone pain
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    Musculoskeletal pain
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    Flank pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Groin pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Joint swelling
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Muscle spasms
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Neck pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Pain in jaw
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    Fungal infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 11 (27.27%)
    5 / 11 (45.45%)
         occurrences all number
    3
    5
    Hypokalaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    Hypercalcaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Hyperuricaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Hypomagnesaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Hypochloraemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Apr 2017
    Amendment 1.1: The rationale for making this change from a Phase 3 potential registration study to a Phase 2 proof of concept study, that it is not intended to support a marketing application, follows from a corporate project portfolio review at Merrimack.
    28 Apr 2017
    Amendment 1.2: Minor administrative changes.

    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 (Merrimack Pharmaceuticals, INC.) terminated the trial early due to business decision.
    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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