HER2 Expression Detection in Breast Cancer Using 99mTc-NM-02

NCT04040686 | Completed Early Phase 1

• 1 other identifier: [2019]52
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

A 99mTc-labeled anti-HER2-sdAb (99mTc-NM-02) will be developed for SPECT/CT assessment of HER2 expression in breast cancer patients. Its safety, radiation dosimetry and biodistribution, and the relationship between tumor uptake and HER2 immunohistochemistry results will be investigated.

Conditions

Breast Cancer

Keywords

HER2; single domain antibody (sdAb); SPECT/CT imaging

Outcome Measures

Primary Outcomes (4)

• Visual Assessment of HER2 expression in Breast cancer using 99mTc-NM-02 SPECT/CT Scan

  Visual analysis will be carried out by 4 experienced nuclear medicine physicians to observe the uptake of 99m-Tc-NM-02 in breast malignant 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 Breast and other Metastatic Lesions in 99mTc-NM-02 SPECT/CT Scan

  Each subject will be administered 3-12 MBq/kg of 99mTc-NM-02 and the semiquantitative analysis of the region of interest (ROI) will be performed in breast and other metastatic lesions. Higher level of HER2 expression (Tumor proportion score, TPS), higher ROI in tumor.

  1 year

• Safety of 99mTc-NM02 through Adverse Event Monitoring

  Subjects will be observed for safety after administration of 99mTc-NM-02, and will do follow up at 48h p.i. Subjects will do blood test to observe for abnormalities in clinical parameters and compare to baseline results.

  2 days

• Safety of 99m-Tc-NM-02 through Adverse Event Monitoring

  Subjects will be observed for safety after administration of 99mTc-NM-02, and will do follow up at 7d p.i. Subjects will be contacted by investigator by phone and asked several questions related to subject's health after 99m-Tc-NM-02 injection and concomitant drugs.

  7 days

Secondary Outcomes (1)

• HER2 Expression Heterogeneity

  1 year

Study Arms (1)

Injection of 99mTc-NM-02

EXPERIMENTAL

All breast cancer patients recruited to the study will be administered 3-12 MBq/kg of 99m-Tc-NM-02 (99m-Tc labeled anti-HER2 sdAb) in a single dose injection

Drug: Injection of 99mTc-NM-02

Interventions

Injection of 99mTc-NM-02 DRUG

Patient will be injected with microdose (\<100ug) of 99mTc-NM-02 radiotracer

Also known as: anti-HER2 SPECT/CT radiotracer

Injection of 99mTc-NM-02

Eligibility Criteria

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

You may qualify if:

• Adult female, age 18 years or older
• Prior diagnosis of breast cancer
• Willing to participate in this study and given written informed consent
• AST, ALT, BUN, Cr not more than double the normal values
• Subjects of childbearing potential must be willing to undergo a pregnancy test prior to enrolment

You may not qualify if:

• Pregnancy (subjects with a positive pregnancy test at baseline screening period or who are planning to become pregnant during the study period)
• Breastfeeding (subjects in lactation)
• No biopsy tissue sample can be provided for HER2 expression detection
• Subjects with pacemakers
• Hepatitis B virus infection (including carriers) at screening, ie hepatitis B surface antigen (HBsAg) positive, or hepatitis C antibody (anti-HCV) positive, or acquired immunodeficiency disease (HIV) infected, or serum syphilis positive person
• Abnormal liver function during baseline screening period : AST or ALT\> 2 times the upper limit of normal value (ULN), if the marginal increase of a single index is judged as having no clinical significance by the investigator, it can be retested during the screening period. Once, if ≤ 2 times ULN after retesting, consider enrolling).
• Impaired renal function during screening: serum creatinine or urea nitrogen \> 1.5 times ULN.
• Within 4 months prior to the baseline screening period , myocardial infarction or other cardiac events requiring hospitalization (unstable angina, etc.), cerebrovascular accident, transient ischemic attack, acute congestive Heart failure or severe arrhythmia (ventricular arrhythmia, atrioventricular block above II)
• Subjects with pulmonary embolism or deep vein thrombosis
• Various infections that the investigators consider unsuitable for study, including but not limited to patients with various infections requiring further treatment, such as urinary tract infections, respiratory infections, and diabetic foot infections.
• Patients with abnormal thyroid function during baseline screening period (including but not limited to active hyperthyroidism, hypothyroidism or Hashimoto's thyroiditis)

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, Shanghai Municipality, 200080, China

Location

Related Publications (12)

• Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nat Med. 2016 Jul;22(7):723-6. doi: 10.1038/nm.4120. Epub 2016 Jun 6.

  PMID: 27270588 BACKGROUND

• Burstein HJ. The distinctive nature of HER2-positive breast cancers. N Engl J Med. 2005 Oct 20;353(16):1652-4. doi: 10.1056/NEJMp058197. No abstract available.

  PMID: 16236735 BACKGROUND

• Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L. Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol. 2011 Nov 29;9(1):16-32. doi: 10.1038/nrclinonc.2011.177.

  PMID: 22124364 BACKGROUND

• Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortes J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. doi: 10.1056/NEJMoa1413513.

  PMID: 25693012 BACKGROUND

• Gingras I, Gebhart G, de Azambuja E, Piccart-Gebhart M. HER2-positive breast cancer is lost in translation: time for patient-centered research. Nat Rev Clin Oncol. 2017 Nov;14(11):669-681. doi: 10.1038/nrclinonc.2017.96. Epub 2017 Aug 1.

  PMID: 28762384 BACKGROUND

• Loibl S, Gianni L. HER2-positive breast cancer. Lancet. 2017 Jun 17;389(10087):2415-2429. doi: 10.1016/S0140-6736(16)32417-5. Epub 2016 Dec 7.

  PMID: 27939064 BACKGROUND

• Niikura N, Liu J, Hayashi N, Mittendorf EA, Gong Y, Palla SL, Tokuda Y, Gonzalez-Angulo AM, Hortobagyi GN, Ueno NT. Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol. 2012 Feb 20;30(6):593-9. doi: 10.1200/JCO.2010.33.8889. Epub 2011 Nov 28.

  PMID: 22124109 BACKGROUND

• Baum RP, Prasad V, Muller D, Schuchardt C, Orlova A, Wennborg A, Tolmachev V, Feldwisch J. Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules. J Nucl Med. 2010 Jun;51(6):892-7. doi: 10.2967/jnumed.109.073239. Epub 2010 May 19.

  PMID: 20484419 BACKGROUND

• D'Huyvetter M, Vincke C, Xavier C, Aerts A, Impens N, Baatout S, De Raeve H, Muyldermans S, Caveliers V, Devoogdt N, Lahoutte T. Targeted radionuclide therapy with A 177Lu-labeled anti-HER2 nanobody. Theranostics. 2014 Apr 25;4(7):708-20. doi: 10.7150/thno.8156. eCollection 2014.

  PMID: 24883121 BACKGROUND

• Pruszynski M, D'Huyvetter M, Bruchertseifer F, Morgenstern A, Lahoutte T. Evaluation of an Anti-HER2 Nanobody Labeled with 225Ac for Targeted alpha-Particle Therapy of Cancer. Mol Pharm. 2018 Apr 2;15(4):1457-1466. doi: 10.1021/acs.molpharmaceut.7b00985. Epub 2018 Mar 7.

  PMID: 29502411 BACKGROUND

• Puttemans J, Dekempeneer Y, Eersels JL, Hanssens H, Debie P, Keyaerts M, Windhorst AD, van der Aa F, Lecocq Q, Breckpot K, Morgenstern A, Bruchertseifer F, Lahoutte T, Devoogdt N, D'Huyvetter M. Preclinical Targeted alpha- and beta--Radionuclide Therapy in HER2-Positive Brain Metastasis Using Camelid Single-Domain Antibodies. Cancers (Basel). 2020 Apr 21;12(4):1017. doi: 10.3390/cancers12041017.

  PMID: 32326199 BACKGROUND

• Zhao L, Liu C, Xing Y, He J, O'Doherty J, Huang W, Zhao J. Development of a 99mTc-Labeled Single-Domain Antibody for SPECT/CT Assessment of HER2 Expression in Breast Cancer. Mol Pharm. 2021 Sep 6;18(9):3616-3622. doi: 10.1021/acs.molpharmaceut.1c00569. Epub 2021 Jul 30.

  PMID: 34328338 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jinhua Zhao, PhD

  Shanghai General Hospital Nuclear Medicine Dept

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 30, 2019
• First Posted: August 1, 2019
• Study Start: July 29, 2019
• Primary Completion: December 31, 2021
• Study Completion: March 30, 2022
• Last Updated: April 14, 2023

Record last verified: 2023-04

Locations

CN (1)