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    Clinical Trial Results:
    A Multicenter Study With an Open-label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of the DNA-PK Inhibitor Peposertib (M3814) in Combination With Capecitabine and RT in Participants With Locally Advanced Rectal Cancer

    Summary
    EudraCT number
    		 2018-002275-18
    Trial protocol
    		 ES   DE   FR   PL   IT  
    Global end of trial date
    21 Feb 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Feb 2023
    First version publication date
    25 Feb 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MS100036_0020
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03770689
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Healthcare KGaA, Darmstadt, Germany
    Sponsor organisation address
    Frankfurter Strasse 250, Darmstadt, Germany, 64293
    Public contact
    Communication Center, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.com
    Scientific contact
    Communication Center, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    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
    21 Feb 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Feb 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main purpose of this study was to define maximum tolerated dose (MTD), recommended Phase II dose (RP2D) safety and tolerability of Peposertib in combination with capecitabine and radiotherapy (RT).
    Protection of trial subjects
    Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Mar 2019
    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
    United States: 11
    Country: Number of subjects enrolled
    Spain: 8
    Worldwide total number of subjects
    19
    EEA total number of subjects
    8
    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)
    13
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study was planned to be conducted in two phases: Phase Ib and Phase II. Phase II of the study was never initiated due to early discontinuation as per sponsor's decision.

    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
    		 Peposertib 50 mg + RT + Capecitabine:
    Arm description
    		 Subjects received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.

    Investigational medicinal product name
    Peposertib
    Investigational medicinal product code
    Other name
    M3814, MSC2490484A
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received peposertib 50 milligram (mg) once daily 5 days per week up to 5.5 weeks.

    Investigational medicinal product name
    Radiotherapy (RT)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Kit for radiopharmaceutical preparation
    Routes of administration
    Soft tissue use
    Dosage and administration details
    Subjects received RT 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks.

    Arm title
    		 Peposertib 100 mg + RT + Capecitabine:
    Arm description
    		 Subjects received peposertib 100 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Peposertib
    Investigational medicinal product code
    Other name
    M3814, MSC2490484A
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received peposertib 100 milligram (mg) once daily 5 days per week up to 5.5 weeks.

    Investigational medicinal product name
    Radiotherapy (RT)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Kit for radiopharmaceutical preparation
    Routes of administration
    Soft tissue use
    Dosage and administration details
    Subjects received RT 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks.

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.

    Arm title
    		 Peposertib 150 mg + RT + Capecitabine:
    Arm description
    		 Subjects received peposertib 150 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Peposertib
    Investigational medicinal product code
    Other name
    M3814, MSC2490484A
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received peposertib 150 milligram (mg) once daily 5 days per week up to 5.5 weeks.

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.

    Investigational medicinal product name
    Radiotherapy (RT)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Kit for radiopharmaceutical preparation
    Routes of administration
    Soft tissue use
    Dosage and administration details
    Subjects received RT 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks.

    Arm title
    		 Peposertib 250 mg + RT + Capecitabine:
    Arm description
    		 Subjects received peposertib 250 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Peposertib
    Investigational medicinal product code
    Other name
    M3814, MSC2490484A
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received peposertib 250 milligram (mg) once daily 5 days per week up to 5.5 weeks.

    Investigational medicinal product name
    Radiotherapy (RT)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Kit for radiopharmaceutical preparation
    Routes of administration
    Soft tissue use
    Dosage and administration details
    Subjects received RT 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks.

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.

    Number of subjects in period 1
    		Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Started
    1
    6
    6
    6
    Pharmacokinetic Analysis Set
    1
    6
    6
    6
    Full Analysis Set (FAS)
    1
    6
    6
    6
    Safety Analysis Set (SAF)
    1
    6
    6
    6
    Completed
    1
    6
    6
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Peposertib 50 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Reporting group title
    Peposertib 100 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 100 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Reporting group title
    Peposertib 150 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 150 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Reporting group title
    Peposertib 250 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 250 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Reporting group values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine: Total
    Number of subjects
    		 1 6 6 6 19
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 1 3 5 4 13
        From 65-84 years
    		 0 3 1 2 6
        85 years and over
    		 0 0 0 0 0
    Sex: Female, Male
    Units: subjects
        Female
    		 0 3 2 3 8
        Male
    		 1 3 4 3 11
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 0 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0
        White
    		 1 6 6 6 19
        More than one race
    		 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 1 1
        Not Hispanic or Latino
    		 1 6 6 5 18
        Unknown or Not Reported
    		 0 0 0 0 0
    Subject analysis sets

    Subject analysis set title
    Overall Subjects
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received peposertib 50 mg, 100 mg, 150 mg and 250 mg in their respective cohort once daily in combination with capecitabine 825 milligram per square meter (mg/m^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Subject analysis set title
    All Subjects
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received peposertib 100 mg, 150 mg and 250 mg in their respective cohort once daily in combination with capecitabine 825 milligram per square meter (mg/m^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Subject analysis set title
    Peposertib 50 mg + RT + Capecitabine
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period. Number of subjects analyzed in 50 mg group for PK outcome is different than PK analysis set. Because 1 subject from peposertib 100 mg took peposertib 50 mg from Fraction Day (FD) 1 through FD 10. PK results for this subject was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg). Number of subjects analyzed for 50 mg dose level in PK outputs that is 2 was therefore higher than non-PK outputs that is 1.

    Subject analysis set title
    Peposertib 100 mg + RT + Capecitabine
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received peposertib 100 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period. Number of subjects analyzed in 100 mg group for PK outcome is different than PK analysis set because 1 subject from peposertib 100 mg took peposertib 50 mg from Fraction Day (FD) 1 through FD 10. PK results for this subject was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg). Number of subjects analyzed for 100 mg dose level in PK outputs that is 5 was therefore lesser than non-PK outputs that is 6.

    Subject analysis set title
    Peposertib 150 mg + RT + Capecitabine
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received peposertib 150 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Subject analysis set title
    Peposertib 250 mg + RT + Capecitabine
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received peposertib 250 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Subject analysis sets values
    		 Overall Subjects All Subjects Peposertib 50 mg + RT + Capecitabine Peposertib 100 mg + RT + Capecitabine Peposertib 150 mg + RT + Capecitabine Peposertib 250 mg + RT + Capecitabine
    Number of subjects
    19
    19
    2
    5
    6
    6
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
    13
        From 65-84 years
    6
        85 years and over
    Age Continuous
    Units:
        
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Sex: Female, Male
    Units: subjects
        Female
        Male
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
        Asian
        Native Hawaiian or Other Pacific Islander
        Black or African American
        White
        More than one race
        Unknown or Not Reported
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
        Not Hispanic or Latino
        Unknown or Not Reported

    End points

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    End points reporting groups
    Reporting group title
    Peposertib 50 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Reporting group title
    Peposertib 100 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 100 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Reporting group title
    Peposertib 150 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 150 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Reporting group title
    Peposertib 250 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 250 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Subject analysis set title
    Overall Subjects
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received peposertib 50 mg, 100 mg, 150 mg and 250 mg in their respective cohort once daily in combination with capecitabine 825 milligram per square meter (mg/m^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Subject analysis set title
    All Subjects
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received peposertib 100 mg, 150 mg and 250 mg in their respective cohort once daily in combination with capecitabine 825 milligram per square meter (mg/m^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Subject analysis set title
    Peposertib 50 mg + RT + Capecitabine
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period. Number of subjects analyzed in 50 mg group for PK outcome is different than PK analysis set. Because 1 subject from peposertib 100 mg took peposertib 50 mg from Fraction Day (FD) 1 through FD 10. PK results for this subject was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg). Number of subjects analyzed for 50 mg dose level in PK outputs that is 2 was therefore higher than non-PK outputs that is 1.

    Subject analysis set title
    Peposertib 100 mg + RT + Capecitabine
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received peposertib 100 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period. Number of subjects analyzed in 100 mg group for PK outcome is different than PK analysis set because 1 subject from peposertib 100 mg took peposertib 50 mg from Fraction Day (FD) 1 through FD 10. PK results for this subject was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg). Number of subjects analyzed for 100 mg dose level in PK outputs that is 5 was therefore lesser than non-PK outputs that is 6.

    Subject analysis set title
    Peposertib 150 mg + RT + Capecitabine
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received peposertib 150 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Subject analysis set title
    Peposertib 250 mg + RT + Capecitabine
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received peposertib 250 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Primary: Number of Subjects Who Experienced Dose Limiting Toxicity (DLT) Confirmed by Safety Monitoring Committee (SMC)

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    End point title
    		 Number of Subjects Who Experienced Dose Limiting Toxicity (DLT) Confirmed by Safety Monitoring Committee (SMC) [1]
    End point description
    DLT are treatment emergent adverse events (TEAEs) possibly related to study treatment by Investigator and/or Sponsor up to completion of treatment. DLT were based on SMC: Adverse drug reaction that is of potential clinical significance ; Any occurrence of drug-induced liver injury meeting the Hy’s law criteria; Any Grade 3 toxicity excluding diarrhea, neutropenia lasting for ≤ 5 days, nausea & vomiting, Grade 3 thrombocytopenia without bleeding; Grade ≥ 4 AEs at least possibly related to study drug, irrespective of duration, excluding: Isolated Grade 4 lymphocytopenia without clinical symptoms; Neutropenia lasting for ≤ 5 days and not associated with fever; Any toxicity related to study drug that causes subject to receive > 80% of planned peposertib, capecitabine or RT dose. Dose escalation (DE) analysis set included all subjects treated in dose escalation cohorts, who received at least 80% of peposertib, 50% of capecitabine, and 80% of RT planned dose and complete DLT period.
    End point type
    Primary
    End point timeframe
    Time from first study intervention up to 19 weeks (including 5.5 weeks of treatment and 13.5 weeks of short term safety follow-up period)
    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: No statistical and comparison analysis were performed in single arm for this endpoint.
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    1
    5
    6
    6
    Units: subjects
    0
    1
    1
    3
    No statistical analyses for this end point

    Secondary: Number of Subjects with Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) Version 5.0

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    End point title
    		 Number of Subjects with Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) Version 5.0
    End point description
    Adverse event (AE) is any untoward medical occurrence in subject administered pharmaceutical product, regardless of relationship with this treatment. Therefore, an AE can be any unfavorable & unintended sign symptom, or disease temporally associated with use of a medicinal product, regardless if it is considered related to medicinal product. Serious AE: an AE that results in: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after treatment start date. It included both serious and non-serious TEAEs. Treatment-related TEAEs: related to study intervention. Number of subjects with TEAEs and treatment related TEAEs were reported. SAF analysis set included all subjects who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Time from first study intervention up to long term safety follow-up period (Up to Month 35)
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    1
    6
    6
    6
    Units: subjects
        Subjects with TEAEs
    1
    6
    6
    6
        Subjects with Treatment-Related TEAEs
    1
    6
    6
    6
    No statistical analyses for this end point

    Secondary: Number of Subjects With Abnormalities [Grade Greater than or equals to (>=) 3] in Laboratory Test Values

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    End point title
    		 Number of Subjects With Abnormalities [Grade Greater than or equals to (>=) 3] in Laboratory Test Values
    End point description
    The laboratory measurements included hematology and biochemistry values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 toxicity grades (where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death). Number of subjects with abnormalities Grade >= 3 in laboratory test values were reported. SAF analysis set included all subjects who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Time from first study intervention up to long term safety follow-up period (Up to Month 35)
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    1
    6
    6
    6
    Units: subjects
    1
    6
    6
    6
    No statistical analyses for this end point

    Secondary: Number of Subjects With Markedly Abnormal Vital Sign Measurements

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    End point title
    		 Number of Subjects With Markedly Abnormal Vital Sign Measurements
    End point description
    Vital sign assessments included assessments of heart rate, diastolic blood pressure, systolic blood pressure, respiratory rate and temperature. Number of subjects with markedly abnormal vital sign measurements were reported. SAF analysis set included all subjects who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Time from first study intervention up to long term safety follow-up period (Up to Month 35)
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    1
    6
    6
    6
    Units: subjects
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings

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    End point title
    		 Number of Subjects With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings
    End point description
    Electrocardiograms (ECG) was obtained after the subject has been in a semi-supine position for at least 5 min. ECG parameters included heart rate, PQ/PR duration, QRS and QT duration, QT Interval. Clinical significance was determined by the investigator. Number of subjects with clinically significant abnormalities in 12-lead ECG were reported. SAF analysis set included all subjects who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Time from first study intervention up to long term safety follow-up period (Up to Month 35)
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    1
    6
    6
    6
    Units: subjects
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Composite Pathological Complete Response (pCR)/ Clinical Complete Response (cCR)

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    End point title
    		 Percentage of Subjects With Composite Pathological Complete Response (pCR)/ Clinical Complete Response (cCR)
    End point description
    pCR: Absence of viable tumor cells in the primary tumor and lymph nodes. Subjects have a pCR if they undergo surgery and no residual cancer is found on histological examination of removed specimen. cCR: Subjects are considered to have a cCR if: Absence of any residual tumor in primary site and draining lymph nodes on imaging with magnetic resonance imaging; No visible lesion at endoscopy except a flat scar, telangiectasia, and/or whitening of mucosa; Absence of any palpable tumor or irregularity on digital rectal examination (DRE) and endoscopic ultrasonography (EUS); If a biopsy is negative. Subjects are considered as responders to composite endpoint pCR/cCR if subject had surgery and had pCR; subject did not undergo surgery but had cCR. Number of subjects with composite pathological complete response (pCR)/ clinical complete response (cCR) were reported. Full analysis set (FAS) include all subjects who are enrolled in the study and received at least 1 dose of treatment.
    End point type
    Secondary
    End point timeframe
    At Week 15
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    1
    6
    6
    6
    Units: subjects
        number (confidence interval 95%)
    0.0 (0.0 to 97.5)
    1 (0.4 to 64.1)
    0.0 (0.0 to 45.9)
    0.0 (0.0 to 45.9)
    No statistical analyses for this end point

    Secondary: Disease-free Survival

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    End point title
    		 Disease-free Survival
    End point description
    Disease-free Survival time, defined as the time from first treatment day to the date of the first documentation of objective progressive disease or death due to any cause, whichever occurs first. Median disease-free survival time was estimated according to Kaplan-Meier method. FAS include all subjects who are enrolled in the study and received at least 1 dose of study intervention. As per the planned analysis, Kaplan-Meier estimates were planned to be presented as overall, together with a summary of associated statistics for this endpoint.
    End point type
    Secondary
    End point timeframe
    Time from first study intervention up to Month 35
    End point values
    		 Overall Subjects
    Number of subjects analysed
    19
    Units: Months
        median (full range (min-max))
    21.2 (0.0 to 23.5)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Pathological Complete Response (pCR)

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    End point title
    		 Percentage of Subjects With Pathological Complete Response (pCR)
    End point description
    pCR is defined as the absence of viable tumor cells in the primary tumor and lymph nodes. Subjects are considered to have a pCR if they undergo surgery and no residual cancer is found on histological examination of the removed specimen. FAS include all subjects who are enrolled in the study and received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    At Week 15
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    1
    6
    6
    6
    Units: subjects
        number (confidence interval 95%)
    0.0 (0.0 to 97.5)
    0.0 (0.0 to 45.9)
    0.0 (0.0 to 45.9)
    0.0 (0.0 to 45.9)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Clinical Complete Response (cCR)

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    End point title
    		 Percentage of Subjects With Clinical Complete Response (cCR)
    End point description
    cCR: It is defined as subjects considered to have a cCR if: 1) Absence of any residual tumor in the primary site and draining lymph nodes on imaging with magnetic resonance; 2) No visible lesion at endoscopy except a flat scar, telangiectasia, and/or whitening of the mucosa; 3) Absence of any palpable tumor or irregularity on digital rectal examination (DRE) and endoscopic ultrasonography (EUS); 4) If a biopsy is taken, it must be negative. FAS include all subjects who are enrolled in the study and received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    At Week 15
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    1
    6
    6
    6
    Units: subjects
        number (confidence interval 95%)
    0.0 (0.0 to 97.5)
    16.7 (0.4 to 64.1)
    16.7 (0.4 to 64.1)
    16.7 (0.4 to 64.1)
    No statistical analyses for this end point

    Secondary: Time from Surgery to Local Recurrence

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    End point title
    		 Time from Surgery to Local Recurrence
    End point description
    Time from surgery to local recurrence defined as time from day of surgery to the date of the first documentation of progression of disease, flagged as local recurrence. Median time from surgery to local recurrence was estimated according to Kaplan-Meier method. FAS include all subjects who are enrolled in the study and received at least 1 dose of study intervention. Here, number of subjects analyzed signifies those subjects who underwent rectal surgery.
    End point type
    Secondary
    End point timeframe
    Time from surgery up to Month 35
    End point values
    		 All Subjects
    Number of subjects analysed
    9 [2]
    Units: months
        median (full range (min-max))
    9.999999 (2.8 to 15.0)
    Notes
    [2] - Due to small number of events Median and CI was not determinable. 9.99999 represents no observation.
    No statistical analyses for this end point

    Secondary: Time from Surgery to Distant Metastasis

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    End point title
    		 Time from Surgery to Distant Metastasis
    End point description
    Time from surgery to distant metastasis defined as time from day of surgery to the date of the first documentation of progression of disease, flagged as distant metastasis. Median time from surgery to distant metastasis was estimated according to Kaplan-Meier method. FAS include all subjects who are enrolled in the study and received at least 1 dose of study intervention. Here, number of subjects analyzed signifies those subjects who underwent rectal surgery.
    End point type
    Secondary
    End point timeframe
    Time from surgery up to 35 months
    End point values
    		 All Subjects
    Number of subjects analysed
    9 [3]
    Units: months
        median (full range (min-max))
    9.999999 (2.8 to 15.0)
    Notes
    [3] - Due to small number of events Median and CI was not determinable. 9.99999 represents no observation.
    No statistical analyses for this end point

    Secondary: Neoadjuvant Rectal (NAR) Score

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    End point title
    		 Neoadjuvant Rectal (NAR) Score
    End point description
    The NAR formula includes the clinical tumor (cT) stage, pathologic tumor (pT), and node (pN) stage according to the tumor, node, metastasis classification system for colorectal cancers. The NAR formula is as follows: [5pN- 3 (cT- pT) + 12]2 / 9.61 NAR score ranges from 0 to 100, whereas a score close to 100 is indicative of a poorer prognosis. FAS include all subjects who are enrolled in the study and received at least 1 dose of study intervention. Here, "Number of subjects analyzed" signifies those subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    At Week 15
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    0 [4]
    2
    2
    5
    Units: score on a scale
        arithmetic mean (standard deviation)
    ( )
    9.4 ( 7.95 )
    13.8 ( 1.69 )
    21.2 ( 12.11 )
    Notes
    [4] - None of the subject was analyzed for this arm.
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration (Cmax) of Peposertib

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Peposertib
    End point description
    Cmax was obtained directly from the concentration versus time curve. One subject was assigned to receive peposertib 100 mg; however, this subject took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this subject was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg). Pharmacokinetic (PK) analysis set included subjects who received at least 1 dose of peposertib and have sufficient peposertib plasma concentration data to enable the calculation of at least 1 PK parameter. Sufficient concentration data is defined as at least 3 valid, post dose, concentration points in the PK profile to obtain any PK parameter.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Fraction Day 1 and Fraction Day 9
    End point values
    		 Peposertib 50 mg + RT + Capecitabine Peposertib 100 mg + RT + Capecitabine Peposertib 150 mg + RT + Capecitabine Peposertib 250 mg + RT + Capecitabine
    Number of subjects analysed
    0 [5]
    5
    6
    6
    Units: nanogram per milliliter (ng/mL)
    geometric mean (geometric coefficient of variation)
        Fraction Day 1
    ( )
    593 ( 55.8 )
    728 ( 24.1 )
    1350 ( 55.5 )
        Fraction Day 9
    ( )
    653 ( 50.4 )
    792 ( 41.8 )
    1760 ( 35.6 )
    Notes
    [5] - None of the subject was analyzed for this arm.
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (tlast) (AUC0-t) of Peposertib

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    End point title
    		 Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (tlast) (AUC0-t) of Peposertib
    End point description
    Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. PK analysis set was used. One subject was assigned to receive peposertib 100 mg; however, this subject took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this subject was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg). Here, "n" signifies those subjects who were evaluable for specified category at given time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
    End point values
    		 Peposertib 50 mg + RT + Capecitabine Peposertib 100 mg + RT + Capecitabine Peposertib 150 mg + RT + Capecitabine Peposertib 250 mg + RT + Capecitabine
    Number of subjects analysed
    2 [6]
    5
    6
    6
    Units: hour*nanogram per milliliter (h*ng/mL)
    geometric mean (geometric coefficient of variation)
        Fraction Day 1, n= 2, 5, 6, 6
    9.999999 ( 9.9999 )
    2950 ( 69.8 )
    4000 ( 33.3 )
    7300 ( 71.1 )
        Fraction Day 9, n= 2, 5, 5, 6
    9.999999 ( 9.9999 )
    3450 ( 81.9 )
    5540 ( 51.0 )
    9450 ( 50 )
    Notes
    [6] - 9.99999 represents that there was no observation.
    No statistical analyses for this end point

    Secondary: Time to Reach Maximum Plasma Concentration (tmax) of Peposertib

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    End point title
    		 Time to Reach Maximum Plasma Concentration (tmax) of Peposertib
    End point description
    Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. PK analysis set was used. One subject was assigned to receive peposertib 100 mg; however, this subject took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this subject was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg). PK analysis set was used. One subject was assigned to receive peposertib 100 mg; however, this subject took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this subject was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg). Here, "Number of subjects analyzed" signifies those subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
    End point values
    		 Peposertib 50 mg + RT + Capecitabine Peposertib 100 mg + RT + Capecitabine Peposertib 150 mg + RT + Capecitabine Peposertib 250 mg + RT + Capecitabine
    Number of subjects analysed
    2 [7]
    5
    6
    6
    Units: hours
    median (full range (min-max))
        Fraction Day 1
    3.99999 (3 to 4)
    1 (0.83 to 2)
    2.33 (1.07 to 2.97)
    2.43 (0.85 to 4.00)
        Fraction Day 9
    2.99999 (2 to 3.22)
    2.05 (0.83 to 2.25)
    2.09 (1.07 to 3.82)
    2.01 (0.92 to 7.33)
    Notes
    [7] - 3.99999 and 2.99999 represents that there was no observation
    No statistical analyses for this end point

    Secondary: Total Body Clearance Following Oral Administration (CL/f) of Peposertib

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    End point title
    		 Total Body Clearance Following Oral Administration (CL/f) of Peposertib
    End point description
    The apparent total body clearance of study intervention following extravascular administration on FD1, taking into account the fraction of dose absorbed. CL/f = Dose oral (p.o.)/AUC0-inf. The predicted AUC0-inf should be used. PK analysis set was used. Here, "Number of subjects" analyzed signifies those subjects who were evaluable for this outcome measure. Here, "Number Analyzed" signified those subjects who were evaluable at specified timepoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    0 [8]
    5
    6
    5
    Units: Liter per hour
        geometric mean (geometric coefficient of variation)
    ( )
    31.7 ( 74.5 )
    34.5 ( 41.1 )
    33.0 ( 87.6 )
    Notes
    [8] - None of the subject was analyzed for this arm.
    No statistical analyses for this end point

    Secondary: Apparent Volume of Distribution (Vz/f) of Peposertib

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    End point title
    		 Apparent Volume of Distribution (Vz/f) of Peposertib
    End point description
    The apparent volume of distribution during the terminal phase following extravascular administration, based on the fraction of dose absorbed. Vz/f = Dose/(AUC0-inf multiplied by Lambda z) following single dose. Vz/f= Dose/(AUCtau*Lambda z) following multiple dose. One subject was assigned to receive peposertib 100 mg; however, this subject took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this subject was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg). PK analysis set was used. Here, "Number of subjects" analyzed signifies those subjects who were evaluable for this outcome measure. Here, "n" signified those subjects who were evaluable at specified timepoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    1 [9]
    5
    6
    5
    Units: Liter
    geometric mean (geometric coefficient of variation)
        Fraction Day 1, n= 0, 5, 6, 5
    9.999999 ( 9.9999 )
    256 ( 60.3 )
    274 ( 25.7 )
    245 ( 64.1 )
        Fraction Day 9, n= 1, 5, 5, 5
    9.999999 ( 9.9999 )
    261 ( 100.8 )
    217 ( 43.7 )
    234 ( 39.7 )
    Notes
    [9] - 9.99999 represents that there was no observation.
    No statistical analyses for this end point

    Secondary: Apparent Terminal Half-life (t1/2) of Peposertib

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    End point title
    		 Apparent Terminal Half-life (t1/2) of Peposertib
    End point description
    Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. One subject was assigned to receive peposertib 100 mg; however, this subject took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this subject was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg). PK analysis set was used. Here, "Number of subjects" analyzed signifies those subjects who were evaluable for this endpoint. Here, "n" signified those subjects who were evaluable at specified timepoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
    End point values
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Number of subjects analysed
    1 [10]
    5
    6
    5
    Units: hours
    geometric mean (geometric coefficient of variation)
        Fraction Day 1, n= 0, 5, 6, 5
    9.999999 ( 9.9999 )
    5.60 ( 22.0 )
    5.51 ( 29.0 )
    5.14 ( 28.7 )
        Fraction Day 9, n= 1, 5, 5, 5
    9.999999 ( 9.9999 )
    6.28 ( 30.8 )
    5.04 ( 61.0 )
    6.12 ( 28.9 )
    Notes
    [10] - 9.99999 represents that there was no observation.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to long term follow-up period (Month 36)
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Peposertib 50 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Reporting group title
    Peposertib 100 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 100 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Reporting group title
    Peposertib 150 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 150 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Reporting group title
    Peposertib 250 mg + RT + Capecitabine:
    Reporting group description
    		 Subjects received peposertib 250 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

    Serious adverse events
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 1 (0.00%)
    3 / 6 (50.00%)
    0 / 6 (0.00%)
    4 / 6 (66.67%)
         number of deaths (all causes)
    0
    1
    1
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Peposertib 50 mg + RT + Capecitabine: Peposertib 100 mg + RT + Capecitabine: Peposertib 150 mg + RT + Capecitabine: Peposertib 250 mg + RT + Capecitabine:
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 1 (100.00%)
    5 / 6 (83.33%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Peripheral embolism
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    General disorders and administration site conditions
    Secretion discharge
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 1 (100.00%)
    5 / 6 (83.33%)
    3 / 6 (50.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    5
    3
    0
    Asthenia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    3 / 6 (50.00%)
         occurrences all number
    0
    0
    1
    3
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Psychiatric disorders
    Personality change
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Investigations
    White blood cell count decreased
         subjects affected / exposed
    0 / 1 (0.00%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 1 (0.00%)
    2 / 6 (33.33%)
    2 / 6 (33.33%)
    3 / 6 (50.00%)
         occurrences all number
    0
    2
    2
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Platelet count decreased
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1
    Injury, poisoning and procedural complications
    Radiation skin injury
         subjects affected / exposed
    1 / 1 (100.00%)
    3 / 6 (50.00%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    1
    3
    2
    0
    Anal injury
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nervous system disorders
    Sciatica
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Dysgeusia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dizziness postural
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dizziness
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Blood and lymphatic system disorders
    Lymphopenia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    2
    1
    Neutropenia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Thrombocytopenia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Anaemia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    4 / 6 (66.67%)
         occurrences all number
    0
    1
    1
    4
    Leukopenia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    1
    2
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    1
    Abdominal distension
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    1 / 1 (100.00%)
    5 / 6 (83.33%)
    3 / 6 (50.00%)
    5 / 6 (83.33%)
         occurrences all number
    1
    5
    3
    5
    Dry mouth
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dyschezia
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Abdominal pain lower
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Anal incontinence
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Anal inflammation
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Flatulence
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Constipation
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    3 / 6 (50.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    3
    1
    Colitis
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rectal ulcer
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Rectal tenesmus
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    5 / 6 (83.33%)
         occurrences all number
    0
    0
    2
    5
    Rectal haemorrhage
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    3 / 6 (50.00%)
         occurrences all number
    0
    0
    2
    3
    Proctitis
         subjects affected / exposed
    1 / 1 (100.00%)
    2 / 6 (33.33%)
    2 / 6 (33.33%)
    3 / 6 (50.00%)
         occurrences all number
    1
    2
    2
    3
    Proctalgia
         subjects affected / exposed
    0 / 1 (0.00%)
    3 / 6 (50.00%)
    3 / 6 (50.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    3
    3
    1
    Nausea
         subjects affected / exposed
    1 / 1 (100.00%)
    4 / 6 (66.67%)
    2 / 6 (33.33%)
    2 / 6 (33.33%)
         occurrences all number
    1
    4
    2
    2
    Haematochezia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rash papular
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin ulcer
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dermatitis
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    0
    2
    Dry skin
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Erythema
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Renal and urinary disorders
    Urinary incontinence
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Urinary hesitation
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haematuria
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Micturition urgency
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dysuria
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Bladder spasm
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Candida infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1
    Vaginal infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Dehydration
         subjects affected / exposed
    0 / 1 (0.00%)
    3 / 6 (50.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Decreased appetite
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    3 / 6 (50.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    3
    2
    Hyponatraemia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    0
    2
    Hypocalcaemia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Apr 2019
    The key changes of the protocol were: 1. To allow for the inclusion of Stage II rectal cancer patients, who may often benefit from concurrent chemoradiation according to clinical practice. 2. To allow for the administration of induction chemotherapy, reflecting evolving clinical practice for locally advanced rectal cancer. 3. To adjust the schedule of visits and evaluations to the standard clinical practice. 4. To adjust the tumor evaluation procedures for locally advanced rectal cancer reflecting evolving clinical practice.
    11 May 2020
    The main purpose of this protocol amendment was to provide clearer and more detailed guidance with regards to key therapeutic interventions, such as induction or adjuvant chemotherapy regimens, study treatment specifications (e.g. radiotherapy techniques), and surgical pathology assessment for pathological complete response.
    06 May 2021
    The protocol amendment was issued to document the premature discontinuation of study.

    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.
    As decided by sponsor study was discontinued prior to the initiation of the Phase II part of the study; therefore, results only from the Phase Ib part of the study was reported.
    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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