<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02978196</url>
  </required_header>
  <id_info>
    <org_study_id>2016KY220</org_study_id>
    <nct_id>NCT02978196</nct_id>
  </id_info>
  <brief_title>99mTc Labeled Anti-PD-L1 sdAb SPECT/CT in Assessment of PD-L1 Expression in NSCLC</brief_title>
  <official_title>99mTc Labeled Anti-PD-L1 sdAb in SPECT/CT Assessment of Programmed Death Ligand-1 Expression in Non-small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NanoMab Technology (UK) Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the safety, dosimetry and efficacy of 99m-Tc labeled anti-PD-L1 single domian&#xD;
      antibody (sdAb) (Product Code Name: 99mTc-NM-01)SPECT/CT in the diagnostic imaging PD-L1&#xD;
      expression in Non-Small Cell Lung Cancer (NSCLC) and compare it with the existing gold&#xD;
      standard &quot;biopsy PD-L1 detection&quot;. It is also to establish a new clinical method of&#xD;
      non-invasive PD-L1 expression detection in NSCLC using 99m-Tc labeled anti-PD-L1 sdAb.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 15, 2018</start_date>
  <completion_date type="Actual">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">December 31, 2022</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Visual Assessment of PD-L1 expression in NSCLC using 99m-Tc-NM-01 SPECT/CT Scan</measure>
    <time_frame>1 year</time_frame>
    <description>Visual analysis will be carried out by 4 experienced nuclear medicine physicians to observe the uptake of 99m-Tc-NM-01 in lung lesions.A 4 point system will be used to interpret the scans for abnormalities. It is categorised as such: score 0, no abnormal increased uptake; score 1, low increased uptake; score 2, moderate increased uptake; score 3, high increased uptake. The lesion will be considered positive for malignancy if the score is 2 or higher.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Semiquantitative Assessment of Lung Lesions in 99m-Tc-NM-01 SPECT/CT Scan</measure>
    <time_frame>1 year</time_frame>
    <description>Each patient will be administered 3-12 MBq/kg of 99m-Tc-NM-01 and the semiquantitative analysis of the region of interest (ROI) will be performed in lung lesions. Higher level of PD-L1 expression (Tumor proportion score, TPS), higher ROI in tumor. No expression TPS &lt; 1%; Low expression TPS 1 - 49%; High expression TPS ≥ 50%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PD-L1 expression levels</measure>
    <time_frame>1 year</time_frame>
    <description>Patients biopsy sample will be tested to confirm the levels of PD-L1 expression using Human PD-L1 ELISA Kit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Drug Reaction Report</measure>
    <time_frame>7 days</time_frame>
    <description>Monitor adverse events within 7 days after the injection and scanning to establish the safety of 99m-Tc-NM-01 in patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>New tumor lesion detection</measure>
    <time_frame>1 year</time_frame>
    <description>SPECT/CT scans using 99m-Tc-NM-01 may detect new tumor areas, which can be further proven by biopsy method in order to rule out any false positive results.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Injection of 99m-Tc-NM-01</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients with NSCLC who have undergone biopsy of primary tumour lesion will be administered 3-12 MBq/kg of 99m-Tc-NM-01 in a single injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Injection of 99m-Tc-NM-01</intervention_name>
    <description>Patient is injected with micro-dose of 99m-Tc-NM-01</description>
    <arm_group_label>Injection of 99m-Tc-NM-01</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant is willing and able to give informed consent for the participation in the&#xD;
             study before any protocol-specific screening procedures are performed&#xD;
&#xD;
          -  Male or female, aged 18-75 years old&#xD;
&#xD;
          -  Previous diagnosis of non-small cell carcinoma, confirmed with pathology tests&#xD;
&#xD;
          -  AST, ALT, BUN, Cr not more than double the normal values&#xD;
&#xD;
          -  Patients with no current history of hepatitis A, hepatitis B, AIDS, tuberculosis and&#xD;
             other infectious diseases&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe infection&#xD;
&#xD;
          -  Unable to provide biopsy sample for testing PD-L1 expression level&#xD;
&#xD;
          -  Patients with pacemakers&#xD;
&#xD;
          -  Pregnant and lactating women&#xD;
&#xD;
          -  Investigators professional decision that the subject should not participate in this&#xD;
             clinical study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shanghai General Hospital</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.</citation>
    <PMID>22658127</PMID>
  </reference>
  <reference>
    <citation>Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, Selby M, Taube JM, Anders R, Chen L, Korman AJ, Pardoll DM, Lowy I, Topalian SL. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010 Jul 1;28(19):3167-75. doi: 10.1200/JCO.2009.26.7609. Epub 2010 Jun 1.</citation>
    <PMID>20516446</PMID>
  </reference>
  <reference>
    <citation>Zhang J, Gao J, Li Y, Nie J, Dai L, Hu W, Chen X, Han J, Ma X, Tian G, Wu D, Shen L, Fang J. Circulating PD-L1 in NSCLC patients and the correlation between the level of PD-L1 expression and the clinical characteristics. Thorac Cancer. 2015 Jul;6(4):534-8. doi: 10.1111/1759-7714.12247. Epub 2015 Mar 5.</citation>
    <PMID>26273411</PMID>
  </reference>
  <reference>
    <citation>Heskamp S, Hobo W, Molkenboer-Kuenen JD, Olive D, Oyen WJ, Dolstra H, Boerman OC. Noninvasive Imaging of Tumor PD-L1 Expression Using Radiolabeled Anti-PD-L1 Antibodies. Cancer Res. 2015 Jul 15;75(14):2928-36. doi: 10.1158/0008-5472.CAN-14-3477. Epub 2015 May 14.</citation>
    <PMID>25977331</PMID>
  </reference>
  <reference>
    <citation>Josefsson A, Nedrow JR, Park S, Banerjee SR, Rittenbach A, Jammes F, Tsui B, Sgouros G. Imaging, Biodistribution, and Dosimetry of Radionuclide-Labeled PD-L1 Antibody in an Immunocompetent Mouse Model of Breast Cancer. Cancer Res. 2016 Jan 15;76(2):472-9. doi: 10.1158/0008-5472.CAN-15-2141. Epub 2015 Nov 10.</citation>
    <PMID>26554829</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <last_update_submitted>April 13, 2023</last_update_submitted>
  <last_update_submitted_qc>April 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
    <investigator_full_name>Zhao Jin Hua, MD</investigator_full_name>
    <investigator_title>Director Department of Nuclear Medicine, Principal Investigator, Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02978196
org study id: 2016KY220
nct id: NCT02978196
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
To evaluate the safety, dosimetry and efficacy of 99m-Tc labeled anti-PD-L1 single domian
      antibody (sdAb) (Product Code Name: 99mTc-NM-01)SPECT/CT in the diagnostic imaging PD-L1
      expression in Non-Small Cell Lung Cancer (NSCLC) and compare it with the existing gold
      standard "biopsy PD-L1 detection". It is also to establish a new clinical method of
      non-invasive PD-L1 expression detection in NSCLC using 99m-Tc labeled anti-PD-L1 sdAb.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Visual Assessment of PD-L1 expression in NSCLC using 99m-Tc-NM-01 SPECT/CT Scan
time frame: 1 year
description: Visual analysis will be carried out by 4 experienced nuclear medicine physicians to observe the uptake of 99m-Tc-NM-01 in lung lesions.A 4 point system will be used to interpret the scans for abnormalities. It is categorised as such: score 0, no abnormal increased uptake; score 1, low increased uptake; score 2, moderate increased uptake; score 3, high increased uptake. The lesion will be considered positive for malignancy if the score is 2 or higher.
measure: Semiquantitative Assessment of Lung Lesions in 99m-Tc-NM-01 SPECT/CT Scan
time frame: 1 year
description: Each patient will be administered 3-12 MBq/kg of 99m-Tc-NM-01 and the semiquantitative analysis of the region of interest (ROI) will be performed in lung lesions. Higher level of PD-L1 expression (Tumor proportion score, TPS), higher ROI in tumor. No expression TPS < 1%; Low expression TPS 1 - 49%; High expression TPS ≥ 50%.
measure: PD-L1 expression levels
time frame: 1 year
description: Patients biopsy sample will be tested to confirm the levels of PD-L1 expression using Human PD-L1 ELISA Kit.
measure: Adverse Drug Reaction Report
time frame: 7 days
description: Monitor adverse events within 7 days after the injection and scanning to establish the safety of 99m-Tc-NM-01 in patients.
measure: New tumor lesion detection
time frame: 1 year
description: SPECT/CT scans using 99m-Tc-NM-01 may detect new tumor areas, which can be further proven by biopsy method in order to rule out any false positive results.
arm group label: Injection of 99m-Tc-NM-01
arm group type: Experimental
description: All patients with NSCLC who have undergone biopsy of primary tumour lesion will be administered 3-12 MBq/kg of 99m-Tc-NM-01 in a single injection.
intervention type: Procedure
intervention name: Injection of 99m-Tc-NM-01
description: Patient is injected with micro-dose of 99m-Tc-NM-01
arm group label: Injection of 99m-Tc-NM-01
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
citation: Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.
PMID: 22658127
citation: Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, Selby M, Taube JM, Anders R, Chen L, Korman AJ, Pardoll DM, Lowy I, Topalian SL. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010 Jul 1;28(19):3167-75. doi: 10.1200/JCO.2009.26.7609. Epub 2010 Jun 1.
PMID: 20516446
citation: Zhang J, Gao J, Li Y, Nie J, Dai L, Hu W, Chen X, Han J, Ma X, Tian G, Wu D, Shen L, Fang J. Circulating PD-L1 in NSCLC patients and the correlation between the level of PD-L1 expression and the clinical characteristics. Thorac Cancer. 2015 Jul;6(4):534-8. doi: 10.1111/1759-7714.12247. Epub 2015 Mar 5.
PMID: 26273411
citation: Heskamp S, Hobo W, Molkenboer-Kuenen JD, Olive D, Oyen WJ, Dolstra H, Boerman OC. Noninvasive Imaging of Tumor PD-L1 Expression Using Radiolabeled Anti-PD-L1 Antibodies. Cancer Res. 2015 Jul 15;75(14):2928-36. doi: 10.1158/0008-5472.CAN-14-3477. Epub 2015 May 14.
PMID: 25977331
citation: Josefsson A, Nedrow JR, Park S, Banerjee SR, Rittenbach A, Jammes F, Tsui B, Sgouros G. Imaging, Biodistribution, and Dosimetry of Radionuclide-Labeled PD-L1 Antibody in an Immunocompetent Mouse Model of Breast Cancer. Cancer Res. 2016 Jan 15;76(2):472-9. doi: 10.1158/0008-5472.CAN-15-2141. Epub 2015 Nov 10.
PMID: 26554829
responsible party type: Principal Investigator
investigator affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
investigator full name: Zhao Jin Hua, MD
investigator title: Director Department of Nuclear Medicine, Principal Investigator, Professor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung