Phase I Evaluation of Immunotoxin LMB-100 Administered by Normothermic, Intrapleural Perfusion Following Cytoreductive Surgery in Participants With Pleural Mesotheliomas, or Pleural Effusions From Cancers Expressing Mesothelin

Inclusion Criteria

• •1. Histologically confirmed by the Laboratory of Pathology (LP), CCR, NCI mesothelinpositive malignancy arising from or metastatic to the pleura that is potentially amenable to cytoreductive surgery (R0-R2) and subsequent intrapleural perfusion based on standard of care (SOC) imaging.
• •2. Participants with biphasic MPM must have a \< 50% sarcomatoid component.
• •3. Participants with MPE from extra-thoracic disease may be eligible provided these sites are controlled and are less threatening than the pleural involvement LENT score \>=2 .
• •4. Participants with stage IV cancers affecting the pleura with MPE must have received firstline standard of care systemic treatment for their malignancies.
• •5. MPM participants must not have received any local or systemic therapy for their disease.
• •6. All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade \<= 1 except hemoglobin (Hgb) \<= Grade 2, alopecia (any grade), and \<= Grade 2 peripheral neuropathy.
• •7. Age \>18 years.
• •8. ECOG performance status of \< 2.
• •9. Participants must have adequate pulmonary reserve evidenced by post-operative predicted FEV1 and adjusted DLCO \>= 40% predicted.
• •10. Room air oxygen saturation \>= 90%; otherwise pCO2 \<= 45 and pO2 \>= 60 on room air arterial blood gas (ABG).
• •11. Adequate organ and marrow function as defined below:
• •* leukocytes \>= 3,000/mcL
• •* absolute neutrophil count \>= 1,500/mcL (without transfusion or cytokine support)
• •* absolute lymphocyte count \> 800/mcL
• •* platelets \>= 100,000/mcL
• •* Hgb \>= 9 g/ dL (with transfusion if necessary, within 1 week prior to treatment)
• •* serum albumin \>= 2.0 mg/dL
• •* AST/ALT \<= 2.5 X institutional ULN
• •* creatinine clearance (eGFR) \>= 50 mL/min/1.73 m\^2 by Cockcroft-Gault formula
• •* INR \<= 1.5 x ULN
• •* TSH, T3 and T4 within normal limits (WNL) per institutional criteria
• •* random serum cortisol within normal limits (WNL) per institutional criteria
• •* total bilirubin \< 1.5 X institutional ULN (excluding Gilbert s Syndrome)
• •12. No active brain metastases. Participants with a history of brain metastases except those with meningeal carcinomatosis or leptomeningeal disease may be eligible for treatment a minimum of 1 week following completion of gamma knife or whole-brain radiotherapy, or 4 weeks
• •following surgical resection of brain metastases provided post-treatment MRI scan reveals no evidence of active disease and no ongoing need for systemic steroids.
• •13. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) at the study entry, for the duration of study treatment and up to 4 months (women) or 2 months (men) after the last dose of the study drug.
• •14. Breastfeeding participants must be willing to discontinue breastfeeding from study enrollment through two months after the LMB-100 perfusion.
• •15. HBV-infected participants must be on antivirals and have HBV DNA \<100 IU/mL. HCV-infected participants can be enrolled if HCV RNA level is undetectable.
• •16. The ability of the participant to understand and the willingness to sign a written informed consent.
• •17. Participants must be enrolled into protocol 06C0014 "Prospective Evaluation of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies".
• •18. Participants must provide acceptable archival tumor samples or have at least 1 focus of disease that is amenable to tumor biopsy if necessary for confirmation of histology, and assessment of mesothelin expression.