Whole Body HER2 Quantification With 89Zr-Trastuzumab PET/CT to Asses Zr-trastuzumab Accumulation in HER2-mutated and HER2-overexpressing Metastatic Non-small Cell Lung Cancer

NCT07436858 | Not Yet Recruiting Phase 1

• 2 other identifiers: N26WBH2026-525568-17-00
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators investigate whether PET imaging with ⁸⁹Zr-trastuzumab can reliably demonstrate the extent of tracer accumulation in tumors of patients with HER2-mutated or HER2-overexpressing non-small cell lung cancer (NSCLC). The aim is to determine whether differences in tracer uptake can be detected between these groups, as translational studies indicate that HER2-mutated tumors may internalize trastuzumab-based agents more efficiently than tumors that solely overexpressed HER2.

Conditions

Lung Cancer (NSCLC); HER2 Expression; HER2 Gene Mutation

Outcome Measures

Primary Outcomes (1)

• Standard uptake values (SUVs) in tumor lesions

  measurable tumor lesions and enlarged lymph nodes (\>20 mm)

  During PET imaging with ⁸⁹Zr-trastuzumab

Secondary Outcomes (4)

• Tumor-to-background ratio (TBR)

  During PET imaging with ⁸⁹Zr-trastuzumab

• Tumor-to-plasma ratio (TPR)

  During PET imaging with ⁸⁹Zr-trastuzumab

• SUVs in tumor lesions

  During PET imaging with ⁸⁹Zr-trastuzumab

• Total expression volume (TEV)

  During PET imaging with ⁸⁹Zr-trastuzumab

Other Outcomes (6)

• Visual PET-based heterogeneity assessment

  During PET imaging with ⁸⁹Zr-trastuzumab

• Intralesion heterogeneity (only for >1.5 cm)

  During PET imaging with ⁸⁹Zr-trastuzumab

• Whole-blood and plasma pharmacokinetics of ⁸⁹Zr-trastuzumab: AUCplasma

  Day 1: 10 minutes, 30 minutes, 1 hour, and 2 hours post-injection, and again on day 4 and day 7 post-injection with ⁸⁹Zr-trastuzumab

Study Arms (1)

HER2-mutated NSCLC cohort and HER2-overexpressing NSCLC cohort

EXPERIMENTAL

Patients with advanced NSCLC carrying an activating HER2 mutation (N=10) Patients with advanced NSCLC whose tumors overexpress HER2, but do not have an activating HER2 mutation (N=10).

Diagnostic Test: PET imaging with ⁸⁹Zr-trastuzumab; Diagnostic Test: Blood sampling for pharmacokinetics

Interventions

PET imaging with ⁸⁹Zr-trastuzumab DIAGNOSTIC_TEST

Participants will receive one injection of ⁸⁹Zr-trastuzumab and undergo a PET/CT scan four days later.

HER2-mutated NSCLC cohort and HER2-overexpressing NSCLC cohort

Blood sampling for pharmacokinetics DIAGNOSTIC_TEST

To assess the pharmacokinetics of ⁸⁹Zr-trastuzumab, the investigators collect blood samples at multiple time points following tracer administration. Samples are drawn at 10 minutes, 30 minutes, 1 hour, and 2 hours post-injection, and again on day 4 and day 7 post-injection.

HER2-mutated NSCLC cohort and HER2-overexpressing NSCLC cohort

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent
• Age≥ 18 years, willing and able to comply with the protocol as judged by the investigator
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 at screening.
• Patients with histologically or cytologically confirmed diagnosis of advanced stage:
• HER2 overexpression, defined as an immunohistochemistry score (IHC) of 2+ or 3+ in at least 10% of tumour cells without an activating HER2 mutation
• HER2 activating (insertion) mutation diagnosed through RNA sequencing (RNAseq)
• Disease progression after at least one line of platinum-based chemotherapy ± immunotherapy and starting (new) systemic treatment.
• Be willing to provide a recent tumor tissue specimen after the last line of therapy. Samples must be of sufficient quantity and of adequate tumor tissue content.
• Able to undergo PET imaging procedures.
• Measurable disease according to RECIST 1.1.
• At least two measurable lesions with a long axis diameter ≥2 cm.
• Adequate organ and bone marrow function within 21 days prior to tracer injection, defines as:
• Laboratory Test Laboratory Value Platelet count ≥100 000/mm3 or ≥100 × 109/L (platelet transfusions are not allowed up to 14 days prior to Cycle 1 Day 1 to meet eligibility) Hemoglobin ≥9.0 g/dL or 5.6 mmol/L (transfusion and/or growth factor support is allowed) Absolute neutrophil count (ANC) ≥1500/mm3 or ≥1.5 × 109/L Aspartate aminotransferase /alanine aminotransferase ≤3 × ULN (if liver metastases are present, ≤5 ×ULN) Total bilirubin ≤1.5 × ULN if no liver metastases (\<3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases Creatinine Creatinine clearance (CrCl) ≥30 mL/min as calculated using the Cockcroft-Gault equation.
• International normalised ratio (INR)/Prothrombin time and activated partial thromboplastin time (aPTT) ≤1.5 × (ULN), except for subjects on coumarinderivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator
• Women aged \<50 years will be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the site.

You may not qualify if:

• Contraindications for systemic treatment (as will be assigned by the treating physician)
• Pregnant or lactating women
• Prior allergic reaction to immunoglobulins or immunoglobulin allergy
• Inability to comply with study procedures
• Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the study results
• Prior treatment with HER2-targeted therapies (except pan HER TKIs).

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (1)

The Netherlands Cancer Institute - Antoni van Leeuwenhoek

Amsterdam, North Holland, 1066CX, Netherlands

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Positron-Emission Tomography; Blood Specimen Collection; Pharmacokinetics

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Image Enhancement; Photography; Radionuclide Imaging; Tomography; Diagnostic Techniques, Radioisotope; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques; Metabolism; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Central Study Contacts

Joop de Langen

CONTACT

+31205129111; j.d.langen@nki.nl

Marianne Mahn, MSc

CONTACT

31205129111; m.mahn@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective explorative imaging

Study Record Dates

• First Submitted: February 17, 2026
• First Posted: February 27, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)