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

Inclusion Criteria

• •1. Provision of informed consent prior to any study specific procedures.
• •2. Have a histologically or cytologically confirmed diagnosis of (locally) advanced stage EGFR mutation positive NSCLC, not amenable for curative intent treatment.
• •3. Have measurable disease according to RECIST 1.1.
• •4. At least two lesions with a long axis diameter ≥2 cm.
• •5. Have received at least one line of EGFR TKI treatment for (locally) advanced stage NSCLC.
• •6. In case the tumor is positive for T790M mutation, prior treatment with a third generation EGFR TKI is mandatory.
• •7. Patients must be ≥18 years of age.
• •8. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 at the time of Screening.
• •9. 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
• •10. 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).
• •1. 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.
• •2. 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.
• •11. 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.
• •12. 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.
• •13. 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.
• •14. 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.
• •b. 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).
• •15. Female subject who is pregnant or breastfeeding or intends to become pregnant during the study.
• •16. Subjects with known human immunodeficiency virus (HIV) infection.
• •17. 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.
• •18. Live virus vaccination 28 days prior to Cycle 1 Day 1.