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

NCT02978196 | Completed Early Phase 1

• 1 other identifier: [2019]310
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• PD-L1 expression levels

  1 year

• Adverse Drug Reaction Report

  7 days

• New tumor lesion detection

  1 year

Study Arms (2)

Injection of 99mTc-NM-01

EXPERIMENTAL

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

Injection of 68Ga-NM-01

EXPERIMENTAL

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

Interventions

Injection of 99mTc-NM-01 PROCEDURE

Patient is injected with micro-dose of 99mTc-NM-01

Injection of 99mTc-NM-01

Injection of 68Ga-NM-01 PROCEDURE

Patient is injected with micro-dose of 68Ga-NM-01

Injection of 68Ga-NM-01

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Shanghai General Hospital

Shanghai, China

Location

Related Publications (7)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Zhao L, Gong J, Liao S, Huang W, Zhao J, Xing Y. Preclinical evaluation and preliminary clinical study of 68Ga-NODAGA-NM-01 for PET imaging of PD-L1 expression. Cancer Imaging. 2025 Jan 27;25(1):6. doi: 10.1186/s40644-025-00826-8.

  PMID: 39871394 DERIVED

• 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.

  PMID: 33259032 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Department of Nuclear Medicine, Principal Investigator, Professor

Study Record Dates

• First Submitted: November 22, 2016
• First Posted: November 30, 2016
• Study Start: February 15, 2018
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: May 17, 2024

Record last verified: 2024-05

Locations

CN (1)