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    Clinical Trial Results:
    An International Multicentre, Open-Label First in Human Phase I/II study to evaluate the safety, tolerability, biodistribution and antitumour activity of 177Lu-3BP-227 for the treatment of subjects with solid tumours expressing neurotensin receptor 1

    Summary
    EudraCT number
    		 2017-001263-20
    Trial protocol
    		 BE   NL  
    Global end of trial date
    28 Apr 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 May 2022
    First version publication date
    08 May 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D-FR-01087-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03525392
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Ipsen Pharma SAS
    Sponsor organisation address
    65, quai Georges Gorse, Boulogne-Billancourt, France, 92100
    Public contact
    Medical Director, Ipsen Pharma SAS, clinical.trials@ipsen.com
    Scientific contact
    Medical Director, Ipsen Pharma SAS, clinical.trials@ipsen.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
    28 Apr 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Apr 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Phase 1: To establish the safety and tolerability of fractionated intravenous (IV) administrations of 177Lu-3BP-227 in participants with unresectable, locally advanced or metastatic cancers expressing neurotensin receptor 1 (NTSR1). Phase 2: To estimate objective response rate (ORR) of fractionated IV administrations of 177Lu-3BP-227 in participants with unresectable, locally advanced or metastatic cancers expressing NTSR1.
    Protection of trial subjects
    The study was conducted under the provisions of the Declaration of Helsinki and in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Consolidated Guideline on Good Clinical Practice and in compliance with Independent Ethics Committees/Institutional Review Boards and informed consent regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 May 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 10
    Country: Number of subjects enrolled
    Switzerland: 1
    Country: Number of subjects enrolled
    United States: 3
    Worldwide total number of subjects
    14
    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)
    5
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This Phase 1/2 first in human study was conducted in participants with unresectable, locally advanced or metastatic solid tumors expressing NTSR1 at 9 investigational sites. The sponsor terminated the study early during Cohort 5 in phase 1 dose escalation; phase 1 dose expansion and phase 2 were not started.

    Pre-assignment
    Screening details
    		 For phase 1, core trial was up to 19 weeks and comprised of 2 treatment cycles. If a participant had clinical benefit, they could receive up to 4 additional cycles after end of core trial (EOCT). Due to early termination, only results of core trial are presented. 14 participants received a therapeutic dose of 177Lu-3BP-227 in phase 1 of the study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq
    Arm description
    		 Participants received 177Lu-3BP-227 2.5 Gigabecquerel (GBq) fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    177Lu-3BP-227
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The study medication formulation consisted of 2.5 GBq of 177Lu-3BP-227 in a total volume of 20 milliliter (mL) that was administered by IV infusion over 20 minutes. If infusion reactions were observed, the infusion rate was to be slowed to around 30 minutes or stopped if the reaction was severe.

    Arm title
    		 Cohort 2: 177Lu-3BP-227 4.0 GBq
    Arm description
    		 Participants received 177Lu-3BP-227 4.0 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    177Lu-3BP-227
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The study medication formulation consisted of 4.0 GBq of 177Lu-3BP-227 in a total volume of 20 mL that was administered by IV infusion over 20 minutes. If infusion reactions were observed, the infusion rate was to be slowed to around 30 minutes or stopped if the reaction was severe.

    Arm title
    		 Cohort 3: 177Lu-3BP-227 5.5 GBq
    Arm description
    		 Participants received 177Lu-3BP-227 5.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    177Lu-3BP-227
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The study medication formulation consisted of 5.5 GBq of 177Lu-3BP-227 in a total volume of 20 mL that was administered by IV infusion over 20 minutes. If infusion reactions were observed, the infusion rate was to be slowed to around 30 minutes or stopped if the reaction was severe.

    Arm title
    		 Cohort 4: 177Lu-3BP-227 6.5 GBq
    Arm description
    		 Participants received 177Lu-3BP-227 6.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    177Lu-3BP-227
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The study medication formulation consisted of 6.5 GBq of 177Lu-3BP-227 in a total volume of 20 mL that was administered by IV infusion over 20 minutes. If infusion reactions were observed, the infusion rate was to be slowed to around 30 minutes or stopped if the reaction was severe.

    Arm title
    		 Cohort 5: 177Lu-3BP-227 7.5 GBq
    Arm description
    		 Participants received 177Lu-3BP-227 7.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    177Lu-3BP-227
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The study medication formulation consisted of 7.5 GBq of 177Lu-3BP-227 in a total volume of 20 mL that was administered by IV infusion over 20 minutes. If infusion reactions were observed, the infusion rate was to be slowed to around 30 minutes or stopped if the reaction was severe.

    Number of subjects in period 1
    		Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq
    Started
    2
    3
    5
    3
    1
    Completed
    1
    2
    2
    0
    0
    Not completed
    1
    1
    3
    3
    1
         Adverse event, non-fatal
    1
    -
    2
    -
    -
         Progressive disease
    -
    1
    1
    3
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: 177Lu-3BP-227 2.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 2.5 Gigabecquerel (GBq) fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 2: 177Lu-3BP-227 4.0 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 4.0 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 3: 177Lu-3BP-227 5.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 5.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 4: 177Lu-3BP-227 6.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 6.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 5: 177Lu-3BP-227 7.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 7.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group values
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq Total
    Number of subjects
    		 2 3 5 3 1 14
    Age categorical
    Units: Subjects
    Age continuous
    99999 = Standard deviation cannot be calculated when only 1 participant analyzed.
    Units: years
        arithmetic mean (standard deviation)
    		 70.0 ± 4.2 64.3 ± 16.2 64.0 ± 7.2 66.3 ± 9.1 77.0 ± 99999 -
    Gender categorical
    Units: Subjects
        Female
    		 0 1 1 2 0 4
        Male
    		 2 2 4 1 1 10
    Race
    Units: Subjects
        Not Collected
    		 2 3 5 0 0 10
        White
    		 0 0 0 3 1 4
        Asian
    		 0 0 0 0 0 0
        Black / African American
    		 0 0 0 0 0 0
        Native Hawaiian / Other Pacific Islander
    		 0 0 0 0 0 0
        American Indian / Alaska Native
    		 0 0 0 0 0 0
        Other
    		 0 0 0 0 0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 0 0 0
        Not Hispanic or Latino
    		 2 3 5 3 1 14

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: 177Lu-3BP-227 2.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 2.5 Gigabecquerel (GBq) fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 2: 177Lu-3BP-227 4.0 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 4.0 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 3: 177Lu-3BP-227 5.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 5.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 4: 177Lu-3BP-227 6.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 6.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 5: 177Lu-3BP-227 7.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 7.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Subject analysis set title
    All Participants
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received 177Lu-3BP-227 dose range of 2.5 to 7.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Primary: Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT)

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    End point title
    		 Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT) [1]
    End point description
    DLTs were defined for a list of predefined study medication-related adverse events (AEs) as specified in the protocol, according to the National Cancer Institute – Common Terminology Criteria for Adverse Events scale version 5.0 (CTCAE v5.0) that occurred during the defined DLT assessment period (during Cycle 1 or 2). Safety population contained all participants who received at least 1 dose of study medication.
    End point type
    Primary
    End point timeframe
    From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks.
    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: Only descriptive statistical analysis was performed for the primary endpoint.
    End point values
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq
    Number of subjects analysed
    2
    3
    5
    3
    1
    Units: participants
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs

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    End point title
    		 Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs
    End point description
    177Lu-3BP-227 uptake in organs and lesions was evaluated centrally, using nuclear medicine images, as part of the dosimetry workflow. Uptake activity for organs of interest (i.e., body, bone marrow, left kidney, right kidney, healthy liver, and spleen) was determined. Dosimetry population included all participants with organ dosimetry data and with no major protocol deviations with an impact on dosimetry analysis. Here, n = number of observations for both cycles.
    End point type
    Secondary
    End point timeframe
    Measurements were performed at 0 to 1 hours, 2 to 4 hours, 16 to 24 hours, 40 to 48 hours, 72 to 96 hours post infusion in each treatment cycle.
    End point values
    		 All Participants
    Number of subjects analysed
    14
    Units: percentage of 177Lu-3BP-227
    median (full range (min-max))
        All cycles: Body (n= 21)
    99.7 (99.2 to 100)
        All cycles: Bone marrow (n= 20)
    1.10 (0.560 to 1.98)
        All cycles: Left kidney (n= 25)
    0.247 (0.130 to 0.409)
        All cycles: Right kidney (n= 25)
    0.227 (0.129 to 0.452)
        All cycles: Healthy liver (n= 20)
    1.01 (0.0760 to 1.84)
        All cycles: Spleen (n= 17)
    0.280 (0.110 to 0.770)
    No statistical analyses for this end point

    Secondary: Phase 1: Maximal Concentration (Cmax) of 177Lu-3BP-227

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    End point title
    		 Phase 1: Maximal Concentration (Cmax) of 177Lu-3BP-227
    End point description
    The pharmacokinetic (PK) sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle. Due to the early termination of the study, 177Lu-3BP-227 PK parameters in blood and organs/lesions were not calculated and related PK summary tables were not produced.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [2]
    Units: not applicable
        arithmetic mean (standard deviation)
    ±
    Notes
    [2] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Time Post Injection to Achieve Cmax of 177Lu-3BP-227

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    End point title
    		 Phase 1: Time Post Injection to Achieve Cmax of 177Lu-3BP-227
    End point description
    The PK sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle. Due to the early termination of the study, 177Lu-3BP-227 PK parameters in blood, urine and organs/lesions were not calculated and related PK summary tables were not produced.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [3]
    Units: not applicable
        median (full range (min-max))
    ( to )
    Notes
    [3] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of 177Lu-3BP-227

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    End point title
    		 Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of 177Lu-3BP-227
    End point description
    The PK sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle. Due to the early termination of the study, 177Lu-3BP-227 PK parameters in blood, urine and organs/lesions were not calculated and related PK summary tables were not produced.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [4]
    Units: not applicable
        arithmetic mean (standard deviation)
    ±
    Notes
    [4] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Half-life (t1/2) of 177Lu-3BP-227

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    End point title
    		 Phase 1: Half-life (t1/2) of 177Lu-3BP-227
    End point description
    The PK sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle. Due to the early termination of the study, 177Lu-3BP-227 PK parameters in blood, urine and organs/lesions were not calculated and related PK summary tables were not produced.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [5]
    Units: not applicable
        median (full range (min-max))
    ( to )
    Notes
    [5] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu- 3BP-227 to Each Discernible Organ

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    End point title
    		 Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu- 3BP-227 to Each Discernible Organ
    End point description
    The absorbed dose to the target lesions and discernible organs (i.e., organs showing uptake) was evaluated by image-based analysis. The organs considered for 177Lu-3BP-227 image-based dosimetry assessment included: healthy liver, total liver, bone marrow, left kidney, right kidney, intestine (large and small), spleen, pancreas, stomach wall, right ovary, left ovary, uterus, right testis, left testis, thymus, right thyroid gland, left thyroid gland, prostate gland and total body. Dosimetry population included all participants with organ dosimetry data and with no major protocol deviations with an impact on dosimetry analysis. Here, n= number of participants analyzed for each specific organ/cycle.
    End point type
    Secondary
    End point timeframe
    From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
    End point values
    		 All Participants
    Number of subjects analysed
    14
    Units: participants
        Cycle 1: Right kidney (n= 14)
    4
        Cycle 1: Left kidney (n= 14)
    3
        Cycle 1: Large intestine (n= 14)
    5
        Cycle 1: Bladder (n= 14)
    2
        Cycle 1: Lymph node (n= 14)
    0
        Cycle 2: Right kidney (n= 11)
    2
        Cycle 2: Left kidney (n= 11)
    2
        Cycle 2: Large intestine (n= 11)
    4
        Cycle 2: Bladder (n= 11)
    2
        Cycle 2: Lymph node (n= 11)
    1
    No statistical analyses for this end point

    Secondary: Phase 1: Specific Absorbed Dose to the Target Lesions of 177Lu-3BP-227

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    End point title
    		 Phase 1: Specific Absorbed Dose to the Target Lesions of 177Lu-3BP-227
    End point description
    The specific absorbed dose to the target lesions was evaluated by image-based analysis. Results for all studied diseases (pancreatic ductal adenocarcinoma and colorectal carcinoma) at all anatomical locations (cervical, intrapelvic, liver, lung, lymphenode, and pancreas) for all cycles (Cycle 1 and 2) are reported. Dosimetry population included all participants with organ dosimetry data and with no major protocol deviations with an impact on dosimetry analysis.
    End point type
    Secondary
    End point timeframe
    From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
    End point values
    		 All Participants
    Number of subjects analysed
    14 [6]
    Units: Gray/GBq
        median (full range (min-max))
    0.183 (0.0551 to 1.21)
    Notes
    [6] - 47 Lesions.
    No statistical analyses for this end point

    Secondary: Phase 1: Specific Absorbed Dose Per Organ of 177Lu-3BP-227

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    End point title
    		 Phase 1: Specific Absorbed Dose Per Organ of 177Lu-3BP-227
    End point description
    The specific absorbed dose per organ was evaluated by image-based analysis. Dosimetry population included all participants with organ dosimetry data and with no major protocol deviations with an impact on dosimetry analysis. Here, n = number of observations for both cycles.
    End point type
    Secondary
    End point timeframe
    From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
    End point values
    		 All Participants
    Number of subjects analysed
    14
    Units: Gray/GBq
    median (full range (min-max))
        All cycles: Bone marrow (n= 25)
    0.0636 (0.0346 to 0.0943)
        All cycles: Healthy liver (n= 25)
    0.0515 (0.0263 to 0.0811)
        All cycles: Left kidney (n= 25)
    0.255 (0.102 to 1.05)
        All cycles: Right kidney (n= 25)
    0.242 (0.118 to 0.943)
    No statistical analyses for this end point

    Secondary: Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227

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    End point title
    		 Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227
    End point description
    The cumulative absorbed dose to the discernible organs (i.e., organs showing uptake) was evaluated by image-based analysis. Dosimetry population included all participants with organ dosimetry data and with no major protocol deviations with an impact on dosimetry analysis. Cumulative absorbed doses on Cycles 1 and 2 are only presented for participants who have performed the 2 cycles.
    End point type
    Secondary
    End point timeframe
    From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
    End point values
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq
    Number of subjects analysed
    1
    3
    3
    3
    1
    Units: Gray
    median (full range (min-max))
        Cycle 2: Bone marrow
    0.326 (0.326 to 0.326)
    0.604 (0.304 to 0.645)
    0.680 (0.391 to 0.837)
    0.820 (0.628 to 1.11)
    0.694 (0.694 to 0.694)
        Cycle 2: Healthy liver
    0.254 (0.254 to 0.254)
    0.353 (0.271 to 0.415)
    0.530 (0.428 to 0.637)
    0.714 (0.469 to 0.927)
    0.571 (0.571 to 0.571)
        Cycle 2: Left kidney
    2.17 (2.17 to 2.17)
    4.19 (1.38 to 6.21)
    3.33 (1.90 to 5.12)
    3.44 (1.90 to 3.48)
    2.95 (2.95 to 2.95)
        Cycle 2: Right kidney
    2.38 (2.38 to 2.38)
    3.39 (1.53 to 5.51)
    2.97 (2.14 to 5.74)
    3.01 (2.00 to 4.67)
    2.92 (2.92 to 2.92)
    No statistical analyses for this end point

    Secondary: Phase 1: Cmax of 3BP-227

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    End point title
    		 Phase 1: Cmax of 3BP-227
    End point description
    The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. Due to the early termination of the study, 3BP-227 PK parameters in plasma and urine were not calculated and related PK summary tables were not produced.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [7]
    Units: not applicable
        arithmetic mean (standard deviation)
    ±
    Notes
    [7] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: AUC of 3BP-227

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    End point title
    		 Phase 1: AUC of 3BP-227
    End point description
    The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. Due to the early termination of the study, 3BP-227 PK parameters in plasma and urine were not calculated and related PK summary tables were not produced.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [8]
    Units: not applicable
        arithmetic mean (standard deviation)
    ±
    Notes
    [8] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: t1/2 of 3BP-227

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    End point title
    		 Phase 1: t1/2 of 3BP-227
    End point description
    The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. Due to the early termination of the study, 3BP-227 PK parameters in plasma and urine were not calculated and related PK summary tables were not produced.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [9]
    Units: not applicable
        median (full range (min-max))
    ( to )
    Notes
    [9] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Clearance of 3BP-227

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    End point title
    		 Phase 1: Clearance of 3BP-227
    End point description
    The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. Due to the early termination of the study, 3BP-227 PK parameters in plasma and urine were not calculated and related PK summary tables were not produced.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [10]
    Units: not applicable
        arithmetic mean (standard deviation)
    ±
    Notes
    [10] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Volume of Distribution of 3BP-227

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    End point title
    		 Phase 1: Volume of Distribution of 3BP-227
    End point description
    The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. Due to the early termination of the study, 3BP-227 PK parameters in plasma and urine were not calculated and related PK summary tables were not produced.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [11]
    Units: not applicable
        arithmetic mean (standard deviation)
    ±
    Notes
    [11] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Cumulative Amount of Unchanged 3BP-227 Excreted Into the Urine

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    End point title
    		 Phase 1: Cumulative Amount of Unchanged 3BP-227 Excreted Into the Urine
    End point description
    The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. Due to the early termination of the study, 3BP-227 PK parameters in plasma and urine were not calculated and related PK summary tables were not produced.
    End point type
    Secondary
    End point timeframe
    For other sites, from the start of the infusion to 6 hours, 6 to 12 hours, 12 to 24 hours, and 24 to 48 hours post infusion of 177Lu-3BP-227 in Cycle 1; For USA sites, from the start of the infusion to 6 hours post infusion of 177Lu-3BP-227 in Cycle 1.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [12]
    Units: not applicable
        arithmetic mean (standard deviation)
    ±
    Notes
    [12] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Renal Clearance of 3BP-227 From Plasma

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    End point title
    		 Phase 1: Renal Clearance of 3BP-227 From Plasma
    End point description
    The CLR of 3BP-227 was evaluated. The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 for each treatment cycle. Due to the early termination of the study, 3BP-227 PK parameters in plasma and urine were not calculated.
    End point type
    Secondary
    End point timeframe
    For other sites, from the start of the infusion to 6 hours, 6 to 12 hours, 12 to 24 hours, and 24 to 48 hours post infusion of 177Lu-3BP-227 in Cycle 1; For USA sites, from the start of the infusion to 6 hours post infusion of 177Lu-3BP-227 in Cycle 1.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [13]
    Units: not applicable
        arithmetic mean (standard deviation)
    ±
    Notes
    [13] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Number of Participants With ORR

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    End point title
    		 Phase 1: Number of Participants With ORR
    End point description
    The ORR was defined as number of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) relative to the total number of evaluable participants. Primary Pharmacodynamic population (for tumor response) included all participants who received at least 2 therapeutic doses of 177Lu-3BP-227 and reached the end of Cycle 2 or EOCT visit with available postbaseline tumor assessment based on RECIST 1.1 and with no major protocol deviations with an impact on the analysis.
    End point type
    Secondary
    End point timeframe
    From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
    End point values
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq
    Number of subjects analysed
    1
    1
    2
    1
    1
    Units: participants
    0
    1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Phase 1: Number of Participants With Disease Control Rate (DCR)

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    End point title
    		 Phase 1: Number of Participants With Disease Control Rate (DCR)
    End point description
    The DCR was defined as number of participants with a BOR characterized as CR, PR or stable disease according to RECIST 1.1 relative to the total number of evaluable participants. Primary Pharmacodynamic population (for tumor response) included all participants who received at least 2 therapeutic doses of 177Lu-3BP-227 and reached the end of Cycle 2 or EOCT visit with available postbaseline tumor assessment based on RECIST 1.1 and with no major protocol deviations with an impact on the analysis.
    End point type
    Secondary
    End point timeframe
    From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
    End point values
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq
    Number of subjects analysed
    1
    1
    2
    1
    1
    Units: participants
    0
    1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Phase 1: Progression-Free Survival (PFS)

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    End point title
    		 Phase 1: Progression-Free Survival (PFS)
    End point description
    The PFS was defined as the time from date of first study medication administration until progression, according to RECIST 1.1. Due to the early termination of the study, survival analysis on PFS was not performed.
    End point type
    Secondary
    End point timeframe
    From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
    End point values
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq
    Number of subjects analysed
    0 [14]
    0 [15]
    0 [16]
    0 [17]
    0 [18]
    Units: participants
    Notes
    [14] - Early termination of the study.
    [15] - Early termination of the study.
    [16] - Early termination of the study.
    [17] - Early termination of the study.
    [18] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Overall Survival (OS)

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    End point title
    		 Phase 1: Overall Survival (OS)
    End point description
    The OS was defined from first study medication administration until death, according to RECIST 1.1. Due to the early termination of the study, survival analysis on OS was not performed.
    End point type
    Secondary
    End point timeframe
    From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
    End point values
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq
    Number of subjects analysed
    0 [19]
    0 [20]
    0 [21]
    0 [22]
    0 [23]
    Units: participants
    Notes
    [19] - Early termination of the study.
    [20] - Early termination of the study.
    [21] - Early termination of the study.
    [22] - Early termination of the study.
    [23] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Metabolic Tumor Response Using Positron Emission Tomography (PET) Response Criteria In Solid Tumors (PERCIST) Version 1.0 or Practical PERCIST

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    End point title
    		 Phase 1: Metabolic Tumor Response Using Positron Emission Tomography (PET) Response Criteria In Solid Tumors (PERCIST) Version 1.0 or Practical PERCIST
    End point description
    Tumor response assessments were planned to perform by the site investigator (local) for the phase 1 and dose escalation part and by independent reader (central) for the phase 2. All fluorine-18 fluorodeoxyglucose-PET images were used for the metabolic tumor response assessments as described in PERCIST version 1.0 by the Investigator and/or independent readers. Due to the early termination of the study, metabolic tumor response was not performed.
    End point type
    Secondary
    End point timeframe
    From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
    End point values
    		 All Participants
    Number of subjects analysed
    0 [24]
    Units: not applicable
        arithmetic mean (standard deviation)
    ±
    Notes
    [24] - Early termination of the study.
    No statistical analyses for this end point

    Secondary: Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9

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    End point title
    		 Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9
    End point description
    Changes in tumor markers in serum relevant and specific to the underlying tumor disease was determined. Pharmacodynamic population included all participants who received at least 1 therapeutic dose and with available post-baseline pharmacodynamics/efficacy data. Here, n = number of participants analyzed at each specific time point, 99999 = no participants analyzed and 9999 = standard deviation cannot be calculated when only 1 participant analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1, Cycle 2 Day 1, EOCT (maximum of 16 weeks) and early withdrawal.
    End point values
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq
    Number of subjects analysed
    2
    3
    5
    3
    1
    Units: international units/milliliter
    arithmetic mean (standard deviation)
        Cycle 1 Day 1 (n= 2, 1, 5, 2, 1)
    50019.00 ± 70683.81
    13.00 ± 9999
    20939.54 ± 46482.66
    1455.50 ± 78.49
    314.70 ± 9999
        Cycle 2 Day 1 (n= 1, 3, 3, 3, 1)
    66.00 ± 9999
    456.33 ± 753.23
    277.90 ± 239.71
    18420.33 ± 27442.99
    490.50 ± 9999
        EOCT (n= 1, 2, 1, 1, 1)
    112.00 ± 9999
    928.00 ± 1294.01
    1166.90 ± 9999
    3532.00 ± 9999
    629.90 ± 9999
        Early withdrawal (n= 0, 0, 2, 1, 0)
    99999 ± 99999
    99999 ± 99999
    64.90 ± 86.41
    8398.00 ± 9999
    99999 ± 99999
    No statistical analyses for this end point

    Secondary: Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen

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    End point title
    		 Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen
    End point description
    Changes in tumor markers in serum relevant and specific to the underlying tumor disease was determined. Pharmacodynamic population included all participants who received at least 1 therapeutic dose and with available post-baseline pharmacodynamics/efficacy data. Here, n = number of participants analyzed at each specific time point, 99999 = no participants analyzed and 9999 = standard deviation cannot be calculated when only 1 participant analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1, Cycle 2 Day 1, EOCT (maximum of 16 weeks) and early withdrawal.
    End point values
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq
    Number of subjects analysed
    2
    3
    5
    3
    1
    Units: microgram per liter
    arithmetic mean (standard deviation)
        Cycle 1 Day 1 (n= 2, 1, 5, 2, 1)
    857.95 ± 1209.22
    117.40 ± 9999
    112.38 ± 94.41
    6.65 ± 7.14
    3.50 ± 9999
        Cycle 2 Day 1 (n= 1, 3, 3, 3, 1)
    3.20 ± 9999
    37.93 ± 41.01
    210.97 ± 213.86
    47.87 ± 62.85
    4.60 ± 9999
        EOCT (n= 1, 2, 1, 1, 1)
    4.30 ± 9999
    75.50 ± 47.09
    321.20 ± 9999
    184.00 ± 9999
    5.10 ± 9999
        Early withdrawal (n= 0, 0, 2, 1, 0)
    99999 ± 99999
    99999 ± 99999
    53.75 ± 23.83
    29.60 ± 9999
    99999 ± 99999
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment-emergent AEs are reported for participants who received the therapeutic dose of 177Lu-32P-227 during the core trial (Cycle 1 Day 1 up to EOCT); maximum of 16 weeks.
    Adverse event reporting additional description
    Safety population contained all participants who received at least 1 dose of study medication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Cohort 1: 177Lu-3BP-227 2.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 2.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 2: 177Lu-3BP-227 4.0 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 4.0 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 3: 177Lu-3BP-227 5.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 5.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 4: 177Lu-3BP-227 6.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 6.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Reporting group title
    Cohort 5: 177Lu-3BP-227 7.5 GBq
    Reporting group description
    		 Participants received 177Lu-3BP-227 7.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period.

    Serious adverse events
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 2 (100.00%)
    2 / 3 (66.67%)
    5 / 5 (100.00%)
    3 / 3 (100.00%)
    0 / 1 (0.00%)
         number of deaths (all causes)
    1
    0
    2
    0
    0
         number of deaths resulting from adverse events
    1
    0
    2
    0
    0
    Injury, poisoning and procedural complications
    Subdural haematoma
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    3 / 5 (60.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Hepatic infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Cohort 1: 177Lu-3BP-227 2.5 GBq Cohort 2: 177Lu-3BP-227 4.0 GBq Cohort 3: 177Lu-3BP-227 5.5 GBq Cohort 4: 177Lu-3BP-227 6.5 GBq Cohort 5: 177Lu-3BP-227 7.5 GBq
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 2 (100.00%)
    3 / 3 (100.00%)
    5 / 5 (100.00%)
    3 / 3 (100.00%)
    0 / 1 (0.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Venous thrombosis
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    Chest pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Fatigue
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    General physical health deterioration
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Pyrexia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Illusion
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Sleep disorder
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 2 (50.00%)
    2 / 3 (66.67%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    4
    0
    0
    0
    Blood bicarbonate decreased
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Blood cholesterol increased
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Blood urea increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 2 (50.00%)
    2 / 3 (66.67%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    4
    0
    0
    0
    Haematocrit decreased
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 2 (50.00%)
    2 / 3 (66.67%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    7
    1
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Platelet count decreased
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    Protein total increased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Red blood cell count decreased
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    4 / 5 (80.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    5
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    4
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Product prescribing error
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 2 (50.00%)
    2 / 3 (66.67%)
    3 / 5 (60.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    4
    6
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    3
    1
    0
    Anal haemorrhage
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Ascites
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Ileus
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Vomiting
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    3
    1
    0
    Hepatobiliary disorders
    Cholestasis
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Jaundice
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Pain of skin
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Dysuria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Pollakiuria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Back pain
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    3
    1
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Polyarthritis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Infections and infestations
    Oral candidiasis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Hypercalcaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    4 / 5 (80.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    8
    0
    0
    Hypernatraemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Hypocalcaemia
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences all number
    1
    0
    3
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Oct 2017
    The protocol was amended to update tumor biopsy inclusion criteria as per review by the Ethical Committee in France.
    09 Nov 2017
    The protocol was amended to incorporate changes to inclusion criteria, dose escalation part, physical examination and electrocardiogram assessments as per review by the Health Authorities in France.
    06 Dec 2017
    The protocol was amended to include Ewing sarcoma as an additional indication in the phase 1/2 study and to provide updated information regarding the study medication.
    02 Mar 2018
    The protocol was amended to give precision on the calculation of the tumor growth rate, information about drug-drug interactions, clarification of discontinuation process, information about infusion rate in response to AEs and increase time for use of contraception for females in the inclusion criteria from 30 days to 6 months, as well as information about spillages.
    17 Jul 2018
    The protocol was amended to improve the determination of the biokinetics of 177Lu-3BP-227 and perform an absolute quantification of radioactivity in target organs. Whole body scans (planar scintigraphy) were added to single photon emission computed tomography during treatment period. Whole body scans would allow the calculation of whole-body time-integrated activity coefficient (“residence time”) that was needed for dosimetry analysis, as it accounts for nonspecific activity in the body. Inclusion criterion was updated to enable the recruitment of participants who did not have a compelling standard-of-care option.
    20 Jun 2019
    The protocol was amended to update personnel (the sponsor-authorized protocol approver and sponsor medical monitor), to update the background information, especially new nonclinical toxicology data, to update the number of participants receiving screening and therapeutic dose, to remove tumor growth rate and add genomic alterations in circulating cell-free DNA and gene mutation status as exploratory objectives and endpoints, to change pharmacokinetic timepoints to improve the clinical feasibility, to specify the biopsy conditions and put them as optional assessments, to remove tumor markers assessments for gastric cancer (serum cancer antigen 72-4) and squamous-cell carcinoma of head and neck (tissue polypeptide antigen), to refine the exclusion criteria regarding body weight, to clarify discontinuation rules, to clarify the duration of the safety follow-up period after the study medication screening dose administration and the reporting of AE collection after the last study medication administration, to specify that death due to disease progression will be reported as an SAE, to specify details on the preparation of the clinical study report, and to add schedule of assessments for screen failure participants. In addition, the recording of safety laboratory test results was changed from recording “any AEs according to National Cancer Institute-CTCAE” to “abnormalities in laboratory test values should only be reported as AEs if any of the following apply: • They resulted in a change in study medication schedule of administration (change in dosage, delay in administration, study medication discontinuation). • They required intervention or a diagnosis evaluation to assess the risk to the participant. • They were considered as clinically significant by the Investigator, or the laboratory test abnormality suggested a disease and/or organ toxicity that was new or had worsened from baseline based on sponsor review.
    12 Jun 2020
    The protocol was amended to update the following: • Clarify the inclusion criteria for participant selection as follows: - To clearly state nonresectable locally advanced disease. - To clearly state that no further suitable treatment options were available for participants eligible for the study. • Allow participants screened and found positive for NTSR1 in the 111In-IPN01087 phase 1 diagnostic study to take part in this study without having the diagnostic dose of 177Lu-3BP-227 during the Screening phase. • Extend the long-term follow-up period from 2 years to a maximum of 5 years or until lost to follow-up, withdrawal of consent or death, whichever occurred first. • Revise the DLT criteria to adequately describe the grading as stated in the CTCAE v5.0 dictionary. • Revise the participant discontinuation rules so if there were life-threatening toxicities outside of the DLT period, treatment was discontinued. • Optimize the dosimetry evaluation through adaptation of the imaging schedule. • Clarify biopsy collection. • Clarify about COVID-19 added following the recent pandemic. • Remove the exploratory endpoint of DNA-double strand breaks in peripheral lymphocytes.

    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.
    The sponsor terminated the study early and phase 1 dose expansion and phase 2 were not started. The decision to terminate the study was not due to any safety or tolerability concern, or any event associated with the use of 177Lu-3BP-227.
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