Whole Body HER3 Quantification With Radiolabelled Patritumab Deruxtecan (HER3-DXd) PET/CT

NCT06222489 | Recruiting Phase 2

• 1 other identifier: N23HDX
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Activity of patritumab deruxtecan (U3-1402; HER3-DXd) has been shown in a phase I/II study in patients with HER3 expressing breast cancer as well as in a phase I study in patients with EGFR TKI refractory EGFR mutation positive NSCLC with a preliminary ORR of 25%. HER3 expression can be seen in multiple tumor types and is therefore an attractive target for antibody drug conjugate (ADC) treatment. However, intra- and intertumor heterogeneity of HER3 expression might be substantial, as is seen for HER2, and might contribute to treatment failure or heterogeneous responses. In addition, HER3 expression is dynamic and has been shown to change over time. In order to identify patients that may benefit most from treatment with patritumab deruxtecan, better knowledge of the in vivo behaviour of the drug is warranted. One way to visualize this behaviour is positron emission tomography (PET) imaging with radiolabelled antibodies (immune-PET). 89Zr-Patritumab deruxtecan PET/CT can assess HER3 expression non-invasively at a whole body level, including sites that may be difficult to biopsy. It also visualizes and quantifies biodistribution of patritumab deruxtecan, thereby obtaining valuable information for safety and toxicity analyses.

Conditions

Non-Small Cell Lung Carcinoma; Advanced Non-Small Cell Squamous Lung Cancer; EGFR Gene Mutation

Keywords

At least one line of systemic treatment

Outcome Measures

Primary Outcomes (1)

• The optimal imaging dose patritumab deruxtecan to co-inject with 89Zr-Patritumab deruxtecan (HER3-DXd), defined by adequate visualisation of the circulation five days after tracer injection.

  Identification of the optimal non-radiolabeled patritumab deruxtecan dose to be co-injected with 89Zr-Patritumab deruxtecan to allow optimal 89Zr-Patritumab deruxtecan PET imaging.

  From the date of cycle 1, day 1 until the date of cycle 1, day 5.

Secondary Outcomes (1)

• SUV of tumor lesions

  From the date of cycle 1, dag 3 or 6 and cycle 1, day 14 or 17 and cycle 1, day 29 or 32.

Study Arms (1)

Patritumab Deruxtecan

OTHER

5.6 mg/kg patritumab deruxtecan every 3 weeks

Drug: 89Zr-Patritumab deruxtecan

Interventions

89Zr-Patritumab deruxtecan DRUG

Day 1, day 3, day 6, day 11 and day 26 of first course

Also known as: Tracer

Patritumab Deruxtecan

Eligibility Criteria

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

You may qualify if:

• Provision of informed consent prior to any study specific procedures.
• Have a histologically or cytologically confirmed diagnosis of (locally) advanced stage EGFR mutation positive NSCLC, not amenable for curative intent treatment.
• Have measurable disease according to RECIST 1.1.
• At least two lesions with a long axis diameter ≥2 cm.
• Have received at least one line of EGFR TKI treatment for (locally) advanced stage NSCLC.
• In case the tumor is positive for T790M mutation, prior treatment with a third generation EGFR TKI is mandatory.
• Patients must be ≥18 years of age.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 at the time of Screening.
• Has adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1, defined as:
• 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 (Hgb) ≥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
• Creatinine clearance (CrCl) ≥30 mL/min as calculated using the Cockcroft-Gault equation or measured CrCl
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤3 × ULN (if liver metastases are present, ≤5 ×ULN)
• Total bilirubin (TBL) ≤1.5 × ULN if no liver metastases (\<3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases)

You may not qualify if:

• Any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screening.
• Clinically severe pulmonary compromise (based on investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
• any underlying pulmonary disorder (eg, pulmonary emboli, severe asthma, severe chronic obstructive lung disease (COPD), restrictive lung disease, pleural effusion);
• any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis); OR prior pneumonectomy.
• Is receiving chronic systemic corticosteroids dosed at \>10 mg prednisone or equivalent or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Subjects who require use of bronchodilators, inhaled steroids, or local steroid injections may be included in the study.
• Evidence of any leptomeningeal disease.
• Has clinically significant corneal disease.
• Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, active infection, psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the Investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.
• Evidence of clinically active spinal cord compression or brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive or treated brain metastases who are asymptomatic (ie, without neurologic signs or symptoms and do not require treatment with corticosteroids or anticonvulsants) may be included in the study. Subjects must have a stable neurologic status for at least 2 weeks prior to Cycle 1 Day 1.
• Inadequate washout period prior to Cycle 1 Day 1, defined as:
• Whole brain radiation therapy \<14 days or stereotactic brain radiation therapy \<7 days.
• Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)), \<14 days or 5 half-lives, whichever is longer.
• Monoclonal antibodies other than immune checkpoint inhibitors, such as bevacizumab (anti-VEGF) and cetuximab (anti-EGFR) \<28 days.
• Immune checkpoint inhibitor therapy \< 21 days.
• Major surgery (excluding placement of vascular access) \< 28 days.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Daiichi Sankyo: collaborator

Study Sites (1)

Antoni van Leeuwenhoek

Amsterdam, North Holland, 1066CX, Netherlands

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Product Labeling

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Product Packaging; Industry; Technology, Industry, and Agriculture

Study Officials

• Joop de Langen, MD

  Antoni van Leeuwenhoek

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joop de Langen, MD

CONTACT

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

Marianne Mahn, MSc

CONTACT

+31205122974; m.mahn@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2024
• First Posted: January 24, 2024
• Study Start: March 3, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: March 6, 2025

Record last verified: 2025-03

Locations

NL (1)