Pembrolizumab in Combination with Chemotherapy and Image-Guided Surgery for the Treatment of Resectable Pleural Malignant Mesothelioma (MPM)

Inclusion Criteria

• Patients must have a histologic diagnosis of previously untreated malignant pleural mesothelioma (MPM) amenable to surgical resection. Both epithelioid and non-epithelioid histologies are eligible
• Willingness and capacity to provide written informed consent for the trial
• >= 18 years of age on day of signing informed consent
• Willingness to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count (ANC) >= 1,500 /mcL (performed within 10 days of treatment initiation)
• Platelets >= 100,000 /mcL (performed within 10 days of treatment initiation)
• Hemoglobin >= 9 g/dL without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 10 days of treatment initiation)
• Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 45 mL/min for subject with creatinine levels > 1.5 x institutional ULN (performed within 10 days of treatment initiation) * (Glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) * Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 10 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =< 2.5 x ULN (performed within 10 days of treatment initiation)
• Albumin >= 2.5 mg/dL (performed within 10 days of treatment initiation)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
• Activated partial thromboplastin Time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
• Female subjects of childbearing potential should have a negative serum pregnancy at the screening visit and within 10 days prior to initiating study therapy
• Female subjects of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study medication * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

Exclusion Criteria

• Current participation in a clinical study or participation in a study of an investigational agent or use of an investigational device within 4 weeks of the first dose of treatment
• Diagnosis of immunodeficiency or receipt of any form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment OR need for chronic systemic steroids (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of trial treatment. (Note: Subjects with asthma or chronic obstructive pulmonary disease that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study.)
• Known history of active TB (bacillus tuberculosis)
• Hypersensitivity to ICG or pembrolizumab or any of their excipients
• Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or failure to recover (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or inability to recover (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent * Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study * Note: If subject underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Known additional invasive malignancy that is progressing or requires active systemic treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Known metastatic disease and/or disease that is otherwise determined to be unresectable
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• History of (non-infectious) pneumonitis that has required steroids
• Pre-existing evidence of treated or symptomatic interstitial lung disease (asymptomatic changes on imagining are permissible)
• Active infection requiring systemic antibiotic, antifungal or antiviral therapy
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Receipt of prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Receipt of a live vaccine within 30 days of planned start of study therapy * Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist [registered trademark]) are live attenuated vaccines, and are not allowed. The timing of coronavirus disease (COVID) vaccination will not affect study eligibility