99mTc/68Ga Labeled Anti-PD-L1 sdAb in Assessment of PD-L1 Expression in NSCLC

99mTc/68Ga Labeled Anti-PD-L1 sdAb in Assessment of Programmed Death Ligand-1 Expression in Non-small Cell Lung Cancer

To evaluate the safety, dosimetry and efficacy of 99mTc/68Ga labeled anti-PD-L1 single domian antibody (sdAb) (Product Code Name: 99mTc-NM-01 and 68Ga-NM-01) 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 99mTc/68Ga labeled anti-PD-L1 sdAb.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Procedure: Injection of 99mTc-NM-01; Procedure: Injection of 68Ga-NM-01

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant is willing and able to give informed consent for the participation in the study before any protocol-specific screening procedures are performed
• Male or female, aged 18-75 years old
• Previous diagnosis of non-small cell carcinoma, confirmed with pathology tests
• AST, ALT, BUN, Cr not more than double the normal values
• Patients with no current history of hepatitis A, hepatitis B, AIDS, tuberculosis and other infectious diseases

Exclusion Criteria:

• Severe infection
• Unable to provide biopsy sample for testing PD-L1 expression level
• Patients with pacemakers
• Pregnant and lactating women
• Investigators professional decision that the subject should not participate in this clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Injection of 99mTc-NM-01; All patients with NSCLC who have undergone biopsy of primary tumour lesion will be administered 3-12 MBq/kg of 99mTc-NM-01 in a single injection.	Procedure: Injection of 99mTc-NM-01; Patient is injected with micro-dose of 99mTc-NM-01
Experimental: Injection of 68Ga-NM-01; All patients with NSCLC who have undergone biopsy of primary tumour lesion will be administered 0.75- 4 MBq/kg of 68Ga-NM-01 in a single injection.	Procedure: Injection of 68Ga-NM-01; Patient is injected with micro-dose of 68Ga-NM-01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Assessment of PD-L1 expression in NSCLC using 99mTc-NM-01 SPECT/CT and 68Ga-NM-01 PET/CT Scan	Visual analysis will be carried out by 4 experienced nuclear medicine physicians to observe the uptake of 99mTc-NM-01 and 68Ga-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.	1 year
Semiquantitative Assessment of Lung Lesions in 99mTc-NM-01 SPECT/CT and 68Ga-NM-01 PET Scan	Patients in the 99mTc-NM-01 group will be administered 3-12 MBq/kg of 99mTc-NM-01 and patients in the 68Ga-NM-01 group will be administered 0.75-4 MBq/kg of 68Ga-NM-01. 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%.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PD-L1 expression levels	Patients biopsy sample will be tested to confirm the levels of PD-L1 expression using Human PD-L1 ELISA Kit.	1 year
Adverse Drug Reaction Report	Monitor adverse events within 7 days after the injection and scanning to establish the safety of 99mTc-NM-01 and 68Ga-NM-01 in patients.	7 days
New tumor lesion detection	99mTc-NM-01 SPECT/CT and 68Ga-NM-01 PET/CT may detect new tumor areas, which can be further proven by biopsy method in order to rule out any false positive results.	1 year

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Collaborators: NanoMab Technology (UK) Limited

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• Hughes DJ, Chand G, Goh V, Cook GJR. Inter- and intraobserver agreement of the quantitative assessment of [99mTc]-labelled anti-programmed death-ligand 1 (PD-L1) SPECT/CT in non-small cell lung cancer. EJNMMI Res. 2020 Dec 1;10(1):145. doi: 10.1186/s13550-020-00734-x.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2018
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: November 22, 2016
• First Submitted That Met QC Criteria: November 28, 2016
• First Posted (Estimated): November 30, 2016

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: [2019]310

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No