Liver Cancer Clinical Trials

∙ Histological diagnosis of non-MSI-H/pMMR CRC

∙ • Subjects who have biology-proven non-MSI-H/pMMR CRC and with radiographic findings suggestive of liver metastases may be eligible.

∙ Resectable liver metastases including:

• synchronous liver metastases (present at the time of diagnosis of MSS CRC) and treatment-naïve

• metachronous liver metastasis (developed after resection of the primary tumor) without prior adjuvant chemotherapy

• metachronous liver metastasis (developed after resection of the primary tumor) with adjuvant chemotherapy completed greater than 3 months from the time of consent.

∙ Surgical candidate for resection

∙ Age ≥ 18 years. Rationale: Because no dosing or adverse event data are currently available on the use of dupilumab in combination with toripalimab in subjects \<18 years of age, children are excluded from this study.

∙ ECOG Performance Status 0-1 (Karnofsky ≥60%,)

∙ • Subjects with performance status \>1 carrying long-term disability (such as cerebral palsy) where the disability is not acute nor progressive, and unlikely to significantly affect their response to therapy may be enrolled at the investigator's discretion

∙ Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception upon study entry, for the duration of study participation, and for 3 months following completion of therapy.

• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

‣ Has not undergone a hysterectomy or bilateral oophorectomy; or

⁃ Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

∙ Ability to understand and the willingness to sign a written informed consent. Legally authorized representatives may sign and give informed consent on behalf of study participants.

∙ Adequate organ and marrow function as defined:

• Hematologic

• o Absolute neutrophil count (ANC) ≥1,000 /mcL

⁃ Platelets ≥75,000 /mcL

⁃ Hemoglobin ≥8 g/dL

• Renal\* o Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated (Creatinine clearance should be calculated per institutional standard) creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥45 mL/min for subjects with creatinine levels \> 1.5 X institutional ULN

• Hepatic\* o Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN; ≤ 3 X ULN for subjects with liver metastases o AST ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases

‣ ALT ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases

⁃ Albumin \>2.5 mg/dL

• Coagulation\*

‣ International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants

⁃ Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PTT is within therapeutic range of intended use of anticoagulants \* If laboratory criteria are not met due to what the investigator determines to be a biologic cause (e.g. Gilbert's syndrome causing elevated bilirubin or excessive muscle mass affecting creatinine) or drug-related cause (e.g. elevating in transaminases due to HAART therapy, elevated INR due to anticoagulation) then the lab values will not be used to exclude subject from this trial. This determination will be made by PI.