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A Study to Test Different Doses of BI 765049 Alone and in Combination With Ezabenlimab in Asian People With Advanced Cancer (Solid Tumours) Positive for B7-H6

Primary Purpose

Gastrointestinal Cancer, Lung Cancer, Pancreatic Cancer

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
BI 765049
Ezabenlimab
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastrointestinal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Signed and dated, written inform consent form (ICF) (ICF1 for B7-H6 testing for all patients except those with colorectal cancer (CRC); ICF2 for all patients) describing the study in accordance with International Council on Harmonisation Good Clinical Practice (ICH-GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses. ≥18 years of age at the time of signature on the ICFs (ICF1 and ICF2). Histologically or cytologically confirmed diagnosis of an advanced, unresectable, and/or metastatic gastrointestinal cancer, colorectal cancer, pancreatic cancer, liver cancer, head and neck cancer, or lung cancer. Disease progression despite conventional treatment, intolerant to or not a candidate for conventional treatment, or with a tumour for which no conventional treatment exists. Agree to the collection of tumour samples (as slides from archival diagnostic samples or fresh tumour biopsies) for confirmation of B7-H6 expression at Screening Visit 02 for colorectal cancer (CRC) patients or at Screening Visit 01 for all other patients. Confirmed B7-H6 expression on tumour tissue sample (archived or fresh tumour biopsy) based on central pathology review except for patients diagnosed with advanced or metastatic colorectal cancer (CRC). Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. At least one evaluable target lesion as defined per response evaluation criteria in solid tumors (RECIST v1.1), outside of the central nervous system (CNS), separate from any lesion(s) identified for tumour biopsy. Tumour lesions that have been irradiated ≥28 days before the start of treatment, and have subsequently had documented progression, may be chosen as target lesions only in the absence of measurable lesions that have not been irradiated. Further inclusion criteria apply Exclusion Criteria: History of a major surgery within 28 days prior to first dose of BI 765049 (major according to the Investigator's assessment). Presence of other active invasive cancers other than the one treated in this trial within 3 years prior to screening, except for appropriately treated basal cell carcinoma of the skin, in situ carcinoma of the uterine cervix, or other local tumours considered cured by local treatment. Known leptomeningeal disease or spinal cord compression due to disease. Require anticoagulant treatment which cannot be safely interrupted, if medically needed for a study procedure (e.g., biopsy) based on the opinion of the Investigator. Any of the following laboratory evidence of hepatitis virus infection. Test results obtained in routine diagnostics are acceptable for screening if done within 14 days before the ICF2 date: positive results of hepatitis B surface (HBs) antigen, presence of hepatitis B core (HBc) antibody together with hepatitis B virus (HBV)-DNA and presence of hepatitis C-RNA Infection requiring systemic antimicrobial, antiviral, antiparasitic, or antifungal therapy at the start of treatment in the trial unless otherwise stipulated. Patients with history of human immunodeficiency virus (HIV) infection who meet one or more of the following criteria: cluster of differentiation 4 (CD4)+ count <350 cells/μL, viral load >400 copies/μL, not receiving antiretroviral therapy, receiving established antiretroviral therapy for less than four weeks prior to the start of study treatment, and history of AIDS-defining opportunistic infections within 12 months prior to start of study treatment. Patients with a history of HIV who do not meet any of the criteria above are eligible to participate, but the patient must be under the care of a HIV/Infectious Diseases specialist, or a HIV/Infectious Diseases specialist must be consulted prior to inclusion. Previous treatment history: previous treatment in this trial or another trial with a B7-H6 targeting agent, treatment with a systemic anti-cancer therapy or investigational drug within 21 days or 5 half-lives (whichever is shorter) of the first administration of BI 765049, and treatment with extensive field radiotherapy including whole brain irradiation within14 days prior to first administration of BI 765049. Further exclusion criteria apply

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Part I: BI 765049

    Part II: BI 765049

    Part III: BI 765049 + ezabenlimab

    Part IV: BI 765049 + ezabenlimab

    Arm Description

    BI 765049 monotherapy - dose escalation

    BI 765049 monotherapy - dose expansion

    BI 765049 + ezabenlimab combination therapy - dose escalation

    BI 765049 + ezabenlimab combination therapy - dose expansion

    Outcomes

    Primary Outcome Measures

    Part I: Occurrence of dose-limiting toxicity (DLTs) during the maximum tolerated dose (MTD) evaluation period for BI 765049 monotherapy
    Part II: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)
    Objective response will be determined by the Investigator in patients with measurable disease and will be defined as the best overall response of complete response (CR) or partial response (PR), from the first administration of trial medication until the earliest of progressive disease (PD), death, last evaluable tumour assessment before the start of subsequent anti-cancer therapy, lost to follow-up, or withdrawal of consent.
    Part III: Occurrence of dose-limiting toxicity (DLTs) during the maximum tolerated dose (MTD) evaluation period for BI 765049 in combination with ezabenlimab
    Part IV: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)

    Secondary Outcome Measures

    Part I: Maximum measured concentration of BI 765049 (Cmax) after first administration
    Part I: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
    Part III: Maximum measured concentration of BI 765049 (Cmax) after the first administration
    Part III: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
    Part I: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after the first administration
    Part I: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations
    Part III: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after the first administration
    Part III: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations
    Part I: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)
    Objective response will be determined by the Investigator in patients with measurable disease who have been treated with either BI 765049 monotherapy or BI 765049 in combination with ezabenlimab and will be defined as the best overall response of complete response (CR) or partial response (PR), according to response evaluation criteria in solid tumors (RECIST v1.1). from the first administration of trial medication until the earliest of progressive disease (PD), death, or last evaluable tumour assessment before the start of subsequent anti-cancer therapy, lost to follow-up, or withdrawal of consent.
    Part III: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)
    Part II: Progression free survival (PFS)
    Progression free survival (PFS) will be defined as the time from first treatment administration until tumour progression according to response evaluation criteria in solid tumors (RECIST v1.1) as determined by the Investigator or death from any cause, whichever occurs earlier.
    Part IV: Progression free survival (PFS)
    Part II: Duration of response
    Duration of response will be defined as the time from a patient's first documented complete response (CR) or partial response (PR), according to response evaluation criteria in solid tumors (RECIST v1.1), until the earliest of disease progression, or death.
    Part IV: Duration of response
    Part II: Disease control
    Disease control will be defined as best overall response of complete response (CR), partial response (PR) or stable disease (SD) where best overall response is as determined by the Investigator according to response evaluation criteria in solid tumors (RECIST v1.1) from the first administration of trial medication until the earliest of progression disease (PD), death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, lost to follow-up, or withdrawal of consent.
    Part IV: Disease control
    Part II: Objective response based on the immune response evaluation criteria in solid tumors (iRECIST)
    Objective response based on immune response evaluation criteria in solid tumors (iRECIST) criteria will be determined by the Investigator in patients with measurable disease and will be defined as the best overall response of complete response (CR) or partial response (PR), from the first administration of trial medication until the earliest of immune confirmed progressive disease (PD), death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, lost to follow-up, or withdrawal of consent.
    Part IV: Objective response based on the immune response evaluation criteria in solid tumors (iRECIST)
    Part II: Maximum measured concentration of BI 765049 (Cmax) after first administration
    Part II: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
    Part IV: Maximum measured concentration of BI 765049 (Cmax) after first administration
    Part IV: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
    Part II: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after first administration
    Part II: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations
    Part IV: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after first administration
    Part IV: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations

    Full Information

    First Posted
    October 16, 2023
    Last Updated
    October 16, 2023
    Sponsor
    Boehringer Ingelheim
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06091930
    Brief Title
    A Study to Test Different Doses of BI 765049 Alone and in Combination With Ezabenlimab in Asian People With Advanced Cancer (Solid Tumours) Positive for B7-H6
    Official Title
    Phase I, Non-randomised, Open-label, Multi-centre Dose Escalation and Expansion Trial of BI 765049 and BI 765049 + Ezabenlimab Administered by Repeated Intravenous Infusion in Asian Patients With Malignant Solid Tumours Expressing B7-H6
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 25, 2023 (Anticipated)
    Primary Completion Date
    November 30, 2025 (Anticipated)
    Study Completion Date
    January 31, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Boehringer Ingelheim

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a study in adults from Asia with different types of advanced cancer (solid tumours). People can join the study if they have cancer of the stomach, large bowel and rectum, pancreas, liver, head and neck or non-small cell lung cancer. This is a study for people for whom previous treatment was not successful or no treatment exists. People can participate if their tumour has the B7-H6 marker. The purpose of this study is to find the highest dose of BI 765049 that people with advanced cancer can tolerate when taken (alone and) together with ezabenlimab. Another purpose is to check whether BI 765049 taken (alone and) together with ezabenlimab can make tumours shrink. Both medicines may help the immune system fight cancer. Participants can stay in the study up to 3 years, as long as they can tolerate it and can benefit from it. During this time, they visit the study site about every 3 weeks. At the study site they get BI 765049 alone or in combination with ezabenlimab as an infusion into a vein. BI 765049 is given in 3-week cycles, ezabenlimab is given once every 3 weeks. The doctors check the health of the participants and note any health problems that could have been caused by BI 765049 or ezabenlimab. Doctors regularly check the size of the tumour and check whether it has spread to other parts of the body.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gastrointestinal Cancer, Lung Cancer, Pancreatic Cancer, Colorectal Cancer, Head and Neck Cancer, Liver Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Model Description
    The trial is divided in four parts. Part I and Part III will have a sequential assignment while Part II and Part IV will have a parallel assignment.
    Masking
    None (Open Label)
    Masking Description
    All trial parts will be conducted open label.
    Allocation
    Non-Randomized
    Enrollment
    70 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Part I: BI 765049
    Arm Type
    Experimental
    Arm Description
    BI 765049 monotherapy - dose escalation
    Arm Title
    Part II: BI 765049
    Arm Type
    Experimental
    Arm Description
    BI 765049 monotherapy - dose expansion
    Arm Title
    Part III: BI 765049 + ezabenlimab
    Arm Type
    Experimental
    Arm Description
    BI 765049 + ezabenlimab combination therapy - dose escalation
    Arm Title
    Part IV: BI 765049 + ezabenlimab
    Arm Type
    Experimental
    Arm Description
    BI 765049 + ezabenlimab combination therapy - dose expansion
    Intervention Type
    Drug
    Intervention Name(s)
    BI 765049
    Intervention Description
    BI 765049
    Intervention Type
    Drug
    Intervention Name(s)
    Ezabenlimab
    Other Intervention Name(s)
    BI 754091
    Intervention Description
    Ezabenlimab
    Primary Outcome Measure Information:
    Title
    Part I: Occurrence of dose-limiting toxicity (DLTs) during the maximum tolerated dose (MTD) evaluation period for BI 765049 monotherapy
    Time Frame
    One treatment cycle, defined as 3 weeks after first administration of BI 765049 or 1 week after the administration of first full dose of BI 765049, whichever is longer
    Title
    Part II: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)
    Description
    Objective response will be determined by the Investigator in patients with measurable disease and will be defined as the best overall response of complete response (CR) or partial response (PR), from the first administration of trial medication until the earliest of progressive disease (PD), death, last evaluable tumour assessment before the start of subsequent anti-cancer therapy, lost to follow-up, or withdrawal of consent.
    Time Frame
    Up to month 36
    Title
    Part III: Occurrence of dose-limiting toxicity (DLTs) during the maximum tolerated dose (MTD) evaluation period for BI 765049 in combination with ezabenlimab
    Time Frame
    From first BI 765049 administration to 1 week after the first ezabenlimab dose
    Title
    Part IV: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)
    Time Frame
    Up to month 36
    Secondary Outcome Measure Information:
    Title
    Part I: Maximum measured concentration of BI 765049 (Cmax) after first administration
    Time Frame
    Up to 1 day
    Title
    Part I: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
    Time Frame
    Up to month 37
    Title
    Part III: Maximum measured concentration of BI 765049 (Cmax) after the first administration
    Time Frame
    Up to 1 day
    Title
    Part III: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
    Time Frame
    Up to month 37
    Title
    Part I: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after the first administration
    Time Frame
    Up to 1 day
    Title
    Part I: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations
    Time Frame
    Up to month 37
    Title
    Part III: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after the first administration
    Time Frame
    Up to 1 day
    Title
    Part III: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations
    Time Frame
    Up to month 37
    Title
    Part I: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)
    Description
    Objective response will be determined by the Investigator in patients with measurable disease who have been treated with either BI 765049 monotherapy or BI 765049 in combination with ezabenlimab and will be defined as the best overall response of complete response (CR) or partial response (PR), according to response evaluation criteria in solid tumors (RECIST v1.1). from the first administration of trial medication until the earliest of progressive disease (PD), death, or last evaluable tumour assessment before the start of subsequent anti-cancer therapy, lost to follow-up, or withdrawal of consent.
    Time Frame
    Up to month 36
    Title
    Part III: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)
    Time Frame
    Up to month 36
    Title
    Part II: Progression free survival (PFS)
    Description
    Progression free survival (PFS) will be defined as the time from first treatment administration until tumour progression according to response evaluation criteria in solid tumors (RECIST v1.1) as determined by the Investigator or death from any cause, whichever occurs earlier.
    Time Frame
    Up to month 36
    Title
    Part IV: Progression free survival (PFS)
    Time Frame
    Up to month 36
    Title
    Part II: Duration of response
    Description
    Duration of response will be defined as the time from a patient's first documented complete response (CR) or partial response (PR), according to response evaluation criteria in solid tumors (RECIST v1.1), until the earliest of disease progression, or death.
    Time Frame
    Up to month 36
    Title
    Part IV: Duration of response
    Time Frame
    Up to month 36
    Title
    Part II: Disease control
    Description
    Disease control will be defined as best overall response of complete response (CR), partial response (PR) or stable disease (SD) where best overall response is as determined by the Investigator according to response evaluation criteria in solid tumors (RECIST v1.1) from the first administration of trial medication until the earliest of progression disease (PD), death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, lost to follow-up, or withdrawal of consent.
    Time Frame
    Up to month 36
    Title
    Part IV: Disease control
    Time Frame
    Up to month 36
    Title
    Part II: Objective response based on the immune response evaluation criteria in solid tumors (iRECIST)
    Description
    Objective response based on immune response evaluation criteria in solid tumors (iRECIST) criteria will be determined by the Investigator in patients with measurable disease and will be defined as the best overall response of complete response (CR) or partial response (PR), from the first administration of trial medication until the earliest of immune confirmed progressive disease (PD), death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, lost to follow-up, or withdrawal of consent.
    Time Frame
    Up to month 36
    Title
    Part IV: Objective response based on the immune response evaluation criteria in solid tumors (iRECIST)
    Time Frame
    Up to month 36
    Title
    Part II: Maximum measured concentration of BI 765049 (Cmax) after first administration
    Time Frame
    Up to 1 day
    Title
    Part II: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
    Time Frame
    Up to month 37
    Title
    Part IV: Maximum measured concentration of BI 765049 (Cmax) after first administration
    Time Frame
    Up to 1 day
    Title
    Part IV: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
    Time Frame
    Up to month 37
    Title
    Part II: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after first administration
    Time Frame
    Up to 1 day
    Title
    Part II: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations
    Time Frame
    Up to month 37
    Title
    Part IV: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after first administration
    Time Frame
    Up to 1 day
    Title
    Part IV: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations
    Time Frame
    Up to month 37

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Signed and dated, written inform consent form (ICF) (ICF1 for B7-H6 testing for all patients except those with colorectal cancer (CRC); ICF2 for all patients) describing the study in accordance with International Council on Harmonisation Good Clinical Practice (ICH-GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses. ≥18 years of age at the time of signature on the ICFs (ICF1 and ICF2). Histologically or cytologically confirmed diagnosis of an advanced, unresectable, and/or metastatic gastrointestinal cancer, colorectal cancer, pancreatic cancer, liver cancer, head and neck cancer, or lung cancer. Disease progression despite conventional treatment, intolerant to or not a candidate for conventional treatment, or with a tumour for which no conventional treatment exists. Agree to the collection of tumour samples (as slides from archival diagnostic samples or fresh tumour biopsies) for confirmation of B7-H6 expression at Screening Visit 02 for colorectal cancer (CRC) patients or at Screening Visit 01 for all other patients. Confirmed B7-H6 expression on tumour tissue sample (archived or fresh tumour biopsy) based on central pathology review except for patients diagnosed with advanced or metastatic colorectal cancer (CRC). Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. At least one evaluable target lesion as defined per response evaluation criteria in solid tumors (RECIST v1.1), outside of the central nervous system (CNS), separate from any lesion(s) identified for tumour biopsy. Tumour lesions that have been irradiated ≥28 days before the start of treatment, and have subsequently had documented progression, may be chosen as target lesions only in the absence of measurable lesions that have not been irradiated. Further inclusion criteria apply Exclusion Criteria: History of a major surgery within 28 days prior to first dose of BI 765049 (major according to the Investigator's assessment). Presence of other active invasive cancers other than the one treated in this trial within 3 years prior to screening, except for appropriately treated basal cell carcinoma of the skin, in situ carcinoma of the uterine cervix, or other local tumours considered cured by local treatment. Known leptomeningeal disease or spinal cord compression due to disease. Require anticoagulant treatment which cannot be safely interrupted, if medically needed for a study procedure (e.g., biopsy) based on the opinion of the Investigator. Any of the following laboratory evidence of hepatitis virus infection. Test results obtained in routine diagnostics are acceptable for screening if done within 14 days before the ICF2 date: positive results of hepatitis B surface (HBs) antigen, presence of hepatitis B core (HBc) antibody together with hepatitis B virus (HBV)-DNA and presence of hepatitis C-RNA Infection requiring systemic antimicrobial, antiviral, antiparasitic, or antifungal therapy at the start of treatment in the trial unless otherwise stipulated. Patients with history of human immunodeficiency virus (HIV) infection who meet one or more of the following criteria: cluster of differentiation 4 (CD4)+ count <350 cells/μL, viral load >400 copies/μL, not receiving antiretroviral therapy, receiving established antiretroviral therapy for less than four weeks prior to the start of study treatment, and history of AIDS-defining opportunistic infections within 12 months prior to start of study treatment. Patients with a history of HIV who do not meet any of the criteria above are eligible to participate, but the patient must be under the care of a HIV/Infectious Diseases specialist, or a HIV/Infectious Diseases specialist must be consulted prior to inclusion. Previous treatment history: previous treatment in this trial or another trial with a B7-H6 targeting agent, treatment with a systemic anti-cancer therapy or investigational drug within 21 days or 5 half-lives (whichever is shorter) of the first administration of BI 765049, and treatment with extensive field radiotherapy including whole brain irradiation within14 days prior to first administration of BI 765049. Further exclusion criteria apply
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Boehringer Ingelheim
    Phone
    1-800-243-0127
    Email
    clintriage.rdg@boehringer-ingelheim.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency
    Links:
    URL
    https://www.mystudywindow.com
    Description
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    A Study to Test Different Doses of BI 765049 Alone and in Combination With Ezabenlimab in Asian People With Advanced Cancer (Solid Tumours) Positive for B7-H6

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