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

Non-Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02978196
• Other study ID #: [2019]310
• Status: Completed
• Phase: Early Phase 1
• Start date: February 15, 2018
• Est. completion date: December 31, 2022

Study information

• Verified date: May 2024
• Source: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Procedure:
• Injection of 99mTc-NM-01
Patient is injected with micro-dose of 99mTc-NM-01
• Injection of 68Ga-NM-01
Patient is injected with micro-dose of 68Ga-NM-01

Locations

Country	Name	City	State
China	Shanghai General Hospital	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine	NanoMab Technology (UK) Limited

Country where clinical trial is conducted

China, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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