Non-Small Cell Lung CarcinomaPhase 2NCT06222489
Whole Body HER3 Quantification With Radiolabelled Patritumab Deruxtecan (HER3-DXd) PET/CT
A Phase 2 study testing 89Zr-Patritumab deruxtecan in people with Non-Small Cell Lung Carcinoma and Advanced Non-Small Cell Squamous Lung Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Carcinoma, Advanced Non-Small Cell Squamous Lung Cancer, EGFR Gene Mutation
- What is being tested?
- 89Zr-Patritumab deruxtecan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteNetherlands
- Study dates
- 3 Mar 2025to 1 May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
- Serum albumin ≥2.5 g/dL or 25 g/L
- Prothrombin time (PT) or Prothrombin time- international normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)/partial thromboplastin time (PTT) ≤1.5 × (ULN), except for subjects on coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator
- Be willing to provide a qualifying tumor tissue specimen. A pretreatment tumor biopsy (if medically feasible) or otherwise archival tumor tissue is required. Samples must be of sufficient quantity and of adequate tumor tissue content (as defined in the Laboratory Manual).
- A Baseline pretreatment tumor biopsy must be of the primary (if intact) and/or metastatic lesion(s) not previously irradiated and amenable to core biopsy. Any serious adverse event (SAE) directly related to the new biopsy should be reported as outlined in Section 8.
- If not medically feasible to collect the pretreatment tumor biopsy, archival tumor tissue not previously irradiated must be collected from a biopsy on or after treatment with the most recent EGFR TKI cancer therapy regimen.
- If the subject is a female of childbearing potential, she must have a negative serum pregnancy test at screening and must be willing to use a highly effective birth control upon enrollment, during the Treatment Period, and for 7 months, following the last dose of study drug. A female is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy) with surgery at least 1 month before the first dose or confirmed by follicle stimulating hormone (FSH) test.
- Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration.
- If male, the subject must be surgically sterile or willing to use a highly effective birth control upon enrollment, during the treatment period, and for at least 4 months following the last dose of study drug.
- Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and for at least 4 months after the final study drug administration.
Who cannot join
- 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.
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- 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.
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation < 28 days or palliative radiation therapy < 14 days.
- Chloroquine or hydroxychloroquine ≤ 14 days.
- Prior treatment with an HER3 antibody and/or antibody drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan).
- Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, grade ≤1 or baseline. Subjects with chronic Grade 2 toxicities may be enrolled at the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee.
- Has known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
- Has any primary malignancy other than locally advanced or metastatic NSCLC within 3 years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated.
- Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1, including:
- QT interval corrected by Fridericia's formula (QTcF) prolongation interval of >470 ms for females and >450 ms for males.
- Left ventricular ejection fraction (LVEF) <50% by either echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan.
- Resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg.
- Myocardial infarction within 6 months.
- New York Heart Association (NYHA) Classes 2 to 4 within 28 days.
- Uncontrolled angina pectoris within 6 months.
- Cardiac arrhythmia requiring antiarrhythmic treatment.
- Active Hepatitis B and/or Hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1, Day 1.
- Subjects with past or resolved Hepatitis B virus (HBV) infection are eligible if: i. Hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR ii. HBsAg positive and HBV DNA viral load is documented to be ≤ 2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases (in the absence of liver metastasis); OR iii. HBsAg positive and HBV DNA viral load is documented to be ≤ 2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with liver metastasis and abnormal transaminases AST/ALT < 3 ULN.
- Subjects with a history of Hepatitis C infection will be eligible for enrollment only if the viral load according to local standards of detection, is documented to be below the level of detection in the absence of anti-viral therapy during the previous 12 weeks (ie, sustained viral response according to the local product label but no less than 12 weeks, whichever is longer).
- Female subject who is pregnant or breastfeeding or intends to become pregnant during the study.
- Subjects with known human immunodeficiency virus (HIV) infection.
- Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's judgment, could affect the safety of the subject; alter the absorption, distribution, metabolism or excretion of the study drug; or confound the assessment of study results.
- Live virus vaccination 28 days prior to Cycle 1 Day 1.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Antoni van Leeuwenhoek
Amsterdam, North Holland, 1066CX
About this study
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
- Being tested
- 89Zr-Patritumab deruxtecan
- Keywords
- At least one line of systemic treatment
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
89Zr-Patritumab deruxtecanDrug
Also called Tracer
Day 1, day 3, day 6, day 11 and day 26 of first course
| Study group | Role | What they receive |
|---|---|---|
| Patritumab Deruxtecan | Other | 5.6 mg/kg patritumab deruxtecan every 3 weeks Receives: Drug: 89Zr-Patritumab deruxtecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From the date of cycle 1, day 1 until the date of cycle 1, day 5.
Secondary outcomes (1)
SUV of tumor lesions
Quantify tumor 89Zr-Patritumab deruxtecan uptake (visually and quantitatively, expressed as SUV).
Measured: From the date of cycle 1, dag 3 or 6 and cycle 1, day 14 or 17 and cycle 1, day 29 or 32.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2024
- Study start3 Mar 2025
- Primary completion1 May 2027 (estimated)
- Study completion1 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CarcinomaStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Daiichi Sankyo
- Responsible party
- Sponsor
- Investigators
- Joop de Langen, MD, Principal investigator, Antoni van Leeuwenhoek
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06222489
- Sponsor's protocol ID
- N23HDX
- Status last verified
- Aug 2026
- First submitted
- 16 Jan 2024
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: To be decided
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Whole Body HER3 Quantification With Radiolabelled Patritumab Deruxtecan (HER3-DXd) PET/CT
- ClinicalTrials.gov ID
- NCT06222489
- Acronym / sponsor ID
- N23HDX
- Conditions
- Non-Small Cell Lung Carcinoma, Advanced Non-Small Cell Squamous Lung Cancer, EGFR Gene Mutation
- Keywords
- At least one line of systemic treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Daiichi Sankyo
- Study start
- 3 Mar 2025 (actual)
- Primary completion
- 1 May 2027 (estimated)
- Study completion
- 1 May 2028 (estimated)
- First posted
- 24 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patritumab Deruxtecan | Other | Drug: 89Zr-Patritumab deruxtecan5.6 mg/kg patritumab deruxtecan every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
Key exclusion criteria (36 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 89Zr-Patritumab deruxtecanAlso: TracerDay 1, day 3, day 6, day 11 and day 26 of first course | Drug | Patritumab Deruxtecan |
Primary outcome
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.
Time frame: From the date of cycle 1, day 1 until the date of cycle 1, day 5.
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.
1 secondary outcome
SUV of tumor lesions
Time frame: From the date of cycle 1, dag 3 or 6 and cycle 1, day 14 or 17 and cycle 1, day 29 or 32.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- Individual participant dataSharing planned: Undecided. To be decided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Joop de Langen, MD principal investigator
Antoni van Leeuwenhoek
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 89Zr-Patritumab deruxtecan in people with Non-Small Cell Lung Carcinoma and Advanced Non-Small Cell Squamous Lung Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joop de Langen, MD (+31205129111, j.d.langen@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: From the date of cycle 1, day 1 until the date of cycle 1, day 5.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.