A Window of Opportunity Study of Patritumab Deruxtecan in Patients With Brain Metastases

Inclusion Criteria

• •1. Participants must have newly diagnosed or recurrent brain metastases, with one of the metastases being surgically resectable. Primary tumor histology must be one of the following solid tumor types:
• •1. Melanoma (cutaneous skin)
• •2. Stomach adenocarcinoma (intestinal subtype)
• •3. Breast invasive carcinoma
• •* ER+/PR+/HER2-
• •* HER2+ (any ER/PR status)
• •* Triple negative (ER-/PR-/HER2-)
• •4. Colorectal adenocarcinoma
• •5. Bladder Urothelial carcinoma
• •6. Ovarian serous cystadenocarcinoma
• •* Serous subtype
• •* Mucinous subtype
• •7. Cholangiocarcinoma
• •8. Prostate adenocarcinoma
• •9. Lung carcinoma
• •* Non-small cell lung cancer (NSCLC)
• •* Small cell lung cancer (SCLC)
• •2. Participant must be asymptomatic or minimally/well-controlled symptomatic from brain metastasis.
• •1. Asymptomatic is defined as free of neurologic signs and symptoms related to metastatic brain lesions and not having required or received systemic corticosteroid therapy within 10 days prior to administration of patritumab deruxtecan.
• •2. Minimally/well-controlled symptomatic is define as having neurologic signs and symptoms may be treated with a total daily dose of no more than 4 mg of dexamethasone (or equivalent) that is stable or tapering for 10 days prior to administration of patritumab deruxtecan. Participants with neurologic signs and symptoms who are not being treated with steroids are eligible and should have no experience of seizure within 10 days prior to administration of patritumab deruxtecan.
• •3. Participant must be willing and eligible for craniotomy.
• •4. Participant or partner(s) meets one of the following criteria:
• •1. If the participant 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, as detailed in Section 16.1.1, 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.
• •2. Female participants 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.
• •3. If male, the participant must be surgically sterile or willing to use a highly effective birth control (Section 16.1.1) upon enrollment, during the treatment period, and for at least 4 months following the last dose of study drug.
• •4. Male participants 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.
• •5. Age ≥ 18 years of age at the time of entry into the study.
• •6. Karnofsky Performance Score (KPS) of 70 or higher.
• •7. Participants must have adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to administration of patritumab deruxtecan, defined 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 (Hgb) ≥9.0 g/dL (transfusion and/or colony stimulating factor support is allowed)
• •* Absolute neutrophil count (ANC) ≥1500/mm3 or ≥1.5 × 109/L
• •* Creatinine Clearance (CrCl) 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
• •* 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 receiving coumadin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator
• •8. A signed informed consent form approved by the Institutional Review Board (IRB) will be required for patient enrollment into the study. Participants must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study
• •9. Ability to undergo MRI
• •b) Participants 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).
• •20. 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
• •21. Subjects with human immunodeficiency virus (HIV) infection.
• •22. Has known hypersensitivity to either the drug substance or inactive ingredients in the drug product.