Neoadjuvant Dupilumab and Toripalimab in MSS CRC Subjects With Resectable Liver Metastases

Exclusion Criteria

• •History of autoimmune disorder with the following exceptions:
• •Vitiligo, alopecia, psoriasis or any chronic skin condition that does not require systemic therapy
• •Hypothyroidism (e.g. following autoimmune thyroiditis) stable on thyroid replacement
• •Celiac disease controlled by diet alone
• •Treatment, for any reason, with an immunomodulatory drug, within 8 weeks from time of consent.
• •Prior treatment with dupilumab within the last 8 weeks.
• •Prior treatment with chemotherapy for MSS CRC or locoregional therapy to the target lesion (that will be biopsied and subsequently resected) within 3 months prior to entering the study.
• •Previous therapy for a different cancer (a different primary) is acceptable.
• •Use of investigational agents for treatment of cancer.
• •Subjects with extrahepatic metastases that are not amendable to resectable or locoregional therapy, for whom the intent of surgery would not be curative.
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (≤10 days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements, as determined the treating investigator.
• •Pregnant or nursing women due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• •Breastfeeding should be discontinued prior to study enrollment.
• •Has a diagnosis of primary immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• •Chronic steroids equivalent to ≤ 10mg prednisone are permitted.
• •Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• •Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is permitted.
• •Has a known additional malignancy that is progressing and requires active 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 or anal cancer, prostate cancer on stable dose of hormonal therapy without rising PSA, and breast cancer treated with curative intent now on hormonal therapy.
• •Has a 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.
• •HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with \<200 CD4+ T cells/microliter in the peripheral blood. HIV testing is mandatory for patients with no known history of HIV. For such patients, HIV testing will be considered SOC.
• •Has known active Hepatitis B (e.g., HBV detected by PCR (\>200 IU/ml) or known active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• •Subjects who started antiviral therapy \>/=14days from baseline are permitted.
• •History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
• •Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps) Principle investigator believes that for one or multiple reasons the subject will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the subject.