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    Clinical Trial Results:
    Phase Ib/II open-label clinical study of intratumoral administration of BO-112 in combination with radiotherapy and nivolumab in patients with metastatic PD-1/PDL-1 refractory non-small cell lung cancer

    Summary
    EudraCT number
    		 2021-006410-36
    Trial protocol
    		 ES  
    Global end of trial date
    31 Oct 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Nov 2025
    First version publication date
    15 Nov 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    BORT-112
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Clínica Universidad de Navarra
    Sponsor organisation address
    Avenida Pio XII, 36, Pamplona, Spain, 31008
    Public contact
    Clínica Universidad de Navarra, Clínica Universidad de Navarra, 34 948255400, ucicec@unav.es
    Scientific contact
    Clínica Universidad de Navarra, Clínica Universidad de Navarra, 34 948255400, ucicec@unav.es
    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
    31 Oct 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Oct 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Safety of repeated IT administrations of BO-112 in metastatic lesions in combination with IV nivolumab and radiotherapy.
    Protection of trial subjects
    N/A
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 May 2022
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Ethical reason
    Long term follow-up duration
    		 12 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 10
    Worldwide total number of subjects
    10
    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)
    8
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The inclusion of the first patient was on 05/10/2022 and the inclusion of the last patient was on 20/09/2023. The lack of more recluited patients (N=30) was caused due to recruitment halts produced by Sponsor internal issues, as well as the finalization of the finantiation.

    Pre-assignment
    Screening details
    		 The screening period will be from Days -28 to 0 (i.e., within 4 weeks before the start of the treatment). The screening assessments will be performed according to the Schedule of Assessments (Protocol, section 1.2)

    Period 1
    Period 1 title
    Cohort A and B (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 A
    Arm description
    		 In the initial cohort A, BO-112 was IT injected on a weekly basis during the first cycle on the accessible lesions. After the first cycle, BO-112 was continue to be IT injected every 2 weeks on the previously treated lesions provided they are still injectable. A maximum of 2 hepatic lesions could be treated with BO-112 at each cycle and a maximum of 5 multisite tumoral lesion in total. The minimum dose to be injected per visit was 1 mg (unless the injected lesion, if solitary, becoma smaller than 10 mm) and the maximum dose was 2 mg at each administration. Distribution of volume of injection was determined based on the size of lesion to be injected according to Table 3. FStereotactic ablative radiotherapy (SABR) was initiated on week 3. Patients was evaluated for DLTs within the first 28 days after the first dose of nivolumab. The analysis of DLTs was be based on the DLT evaluable set.
    Arm type
    		 Safety

    Investigational medicinal product name
    NCT02828098
    Investigational medicinal product code
    BO-112
    Other name
    Polyinosinic:Polycytidylic acid
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intratumoral use
    Dosage and administration details
    The minimum dose injected per visit is 1 mg (unless injected lesion in case of response, if solitary, becomes smaller than 1.5 cm) and the maximum dose is 2 mg (3.4 mL), distributed in the different lesions. Distribution of volume of injection was determined based on the size of lesion to be injected.

    Arm title
    		 Cohort B
    Arm description
    		 Once the cohort A has been completed the safety data will be reviewed by the internal clinical review committee to allow patients in cohort B to receive combined treatment. In this cohort, treatment will be as described in the cohort A, but nivolumab will start on cycle 3 (week 5).
    Arm type
    		 Experimental

    Investigational medicinal product name
    NCT02828098
    Investigational medicinal product code
    BO-112
    Other name
    Polyinosinic:Polycytidylic acid
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intratumoral use
    Dosage and administration details
    The minimum dose injected per visit is 1 mg (unless injected lesion in case of response, if solitary, becomes smaller than 1.5 cm) and the maximum dose is 2 mg (3.4 mL), distributed in the different lesions. Distribution of volume of injection was determined based on the size of lesion to be injected.

    Number of subjects in period 1
    		Cohort A Cohort B
    Started
    7
    3
    Completed
    5
    3
    Not completed
    2
    0
         Adverse event, serious fatal
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort A and B
    Reporting group description
    		 -

    Reporting group values
    		 Cohort A and B Total
    Number of subjects
    		 10 10
    Age categorical
    - Group 1: 18-64 - Group 2: 64+
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 8 8
        From 65-84 years
    		 2 2
        85 years and over
    		 0 0
    Gender categorical
    Units: Subjects
        Female
    		 4 4
        Male
    		 6 6
    Subject analysis sets

    Subject analysis set title
    Nº of TEAEs major to grade 3
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All the recruited subjects (10) have been included on this descriptive analisys. Description: - 4 female, 6 male - Group of age 18-64: 8 - Group of age +64: 2

    Subject analysis set title
    PFS
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    As the N was not completly achieve due to budget and vendor issues, the statistical analysis were not able to be carried. A descriptive analysis was done instead

    Subject analysis sets values
    		 Nº of TEAEs major to grade 3 PFS
    Number of subjects
    10
    2
    Age categorical
    - Group 1: 18-64 - Group 2: 64+
    Units: Subjects
        In utero
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
        Newborns (0-27 days)
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
        Children (2-11 years)
    0
    0
        Adolescents (12-17 years)
    0
    0
        Adults (18-64 years)
    8
    2
        From 65-84 years
    2
    0
        85 years and over
    0
    0
    Age continuous
    Units:
        
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
        Male

    End points

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    End points reporting groups
    Reporting group title
    Cohort A
    Reporting group description
    		 In the initial cohort A, BO-112 was IT injected on a weekly basis during the first cycle on the accessible lesions. After the first cycle, BO-112 was continue to be IT injected every 2 weeks on the previously treated lesions provided they are still injectable. A maximum of 2 hepatic lesions could be treated with BO-112 at each cycle and a maximum of 5 multisite tumoral lesion in total. The minimum dose to be injected per visit was 1 mg (unless the injected lesion, if solitary, becoma smaller than 10 mm) and the maximum dose was 2 mg at each administration. Distribution of volume of injection was determined based on the size of lesion to be injected according to Table 3. FStereotactic ablative radiotherapy (SABR) was initiated on week 3. Patients was evaluated for DLTs within the first 28 days after the first dose of nivolumab. The analysis of DLTs was be based on the DLT evaluable set.

    Reporting group title
    Cohort B
    Reporting group description
    		 Once the cohort A has been completed the safety data will be reviewed by the internal clinical review committee to allow patients in cohort B to receive combined treatment. In this cohort, treatment will be as described in the cohort A, but nivolumab will start on cycle 3 (week 5).

    Subject analysis set title
    Nº of TEAEs major to grade 3
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All the recruited subjects (10) have been included on this descriptive analisys. Description: - 4 female, 6 male - Group of age 18-64: 8 - Group of age +64: 2

    Subject analysis set title
    PFS
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    As the N was not completly achieve due to budget and vendor issues, the statistical analysis were not able to be carried. A descriptive analysis was done instead

    Primary: Primary Endpoint: Safety

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    End point title
    		 Primary Endpoint: Safety
    End point description
    The primary endpoint was to assess the safety of repeated IT administrations of BO-112 in metastatic lesions in combination with IV nivolumab and radiotherapy. Safety is described as: number and proportion of subjects with TEAEs with severity ≥ Grade 3 (NCI-CTCAE v. 5.0) in safety population.
    End point type
    Primary
    End point timeframe
    At the end of the study
    End point values
    		 Cohort A Cohort B
    Number of subjects analysed
    5
    2
    Units: TEAE grade 3 or superior
        number (not applicable)
    5
    2
    Statistical analysis title
    		 Nº of major-or-equal -to-Grade-3 TEAEs
    Statistical analysis description
    71 AE and 8 SAE were regitered during the trial. 1 AE and 4 SAE were cataloged as equal or major than Grade 3.
    Comparison groups
    Cohort B v Cohort A
    Number of subjects included in analysis
    7
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 = 0 [2]
    Method
    		 N/A
    Confidence interval
    Notes
    [1] - Descriptive analysis (Nº of major-or-equal -to-Grade-3 TEAEs)
    [2] - N/A

    Secondary: Secondary Endpoint: Efficacy

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    End point title
    		 Secondary Endpoint: Efficacy
    End point description
    PFS of the patients
    End point type
    Secondary
    End point timeframe
    At the end of the study
    End point values
    		 Cohort A Cohort B
    Number of subjects analysed
    1
    2
    Units: Months
    1
    2
    Statistical analysis title
    		 PFS
    Statistical analysis description
    The analysis is just descriptive. Due to budget and vendor issues, only 8 patients were recruited and only 2 of them completed the 12 months FU indicated on the Protocol. Therefore, statistical analysis is not possible.
    Comparison groups
    Cohort B v Cohort A
    Number of subjects included in analysis
    3
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    P-value
    		 = 0 [4]
    Method
    		 N/A
    Confidence interval
    Notes
    [3] - The 2 patients in follow up have PFS of 17 and 16 months respectively. These were the only 2 patients that completed the 12 months of follow up.
    [4] - N/A

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From C1D1 until 28 days following cessation of study treatment
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28.0
    Reporting groups
    Reporting group title
    Cohort A
    Reporting group description
    		 -

    Reporting group title
    Cohort B
    Reporting group description
    		 -

    Serious adverse events
    		 Cohort A Cohort B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
         number of deaths (all causes)
    2
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Toxicity to various agents
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Post procedural haemorrhage
    Additional description: Post-biopsy bleeding
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
    Additional description: 1 death due to progressive deterioration of tumor disease, 1 death where probable cause is thrombus due to fracture of femur
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Lower limb fracture
    Additional description: Broken femur
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Cohort A Cohort B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    3 / 3 (100.00%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
         occurrences all number
    1
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    2
    Platelet count increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Troponin T increased
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 3 (33.33%)
         occurrences all number
    2
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
    Additional description: 1 tumor bone pain, 1 tumoral pain
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
         occurrences all number
    1
    1
    Injury, poisoning and procedural complications
    Toxicity to various agents
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
         occurrences all number
    1
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    Neuralgia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Thrombocytosis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    5 / 7 (71.43%)
    1 / 3 (33.33%)
         occurrences all number
    5
    1
    PFAPA syndrome
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    Pyrexia
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 3 (33.33%)
         occurrences all number
    3
    1
    Injection site pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    Diarrhoea
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain upper
    Additional description: Epigastralgia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    Gastritis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Odynophagia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
         occurrences all number
    1
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    4 / 7 (57.14%)
    2 / 3 (66.67%)
         occurrences all number
    5
    3
    Productive cough
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    Haemoptysis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Pneumonitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    Pruritus
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    Lower limb fracture
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    Neck pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Dysponesis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Arthralgia
    Additional description: 1 left hip pain, 1 right hip pain, 2 knee pain, 1 left pelvic pain, 2 left iliac region, 1 right shoulder pain
         subjects affected / exposed
    3 / 7 (42.86%)
    3 / 3 (100.00%)
         occurrences all number
    4
    4

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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.
    None reported
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    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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