Nivolumab+Ipilimumab+RT in MSS mCRC

Exclusion Criteria

• •Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days of protocol treatment, or those who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• •Patients who have had radiation within 8 weeks prior to protocol registration.
• •Participants who are receiving any other investigational agents.
• •Patients are excluded if they have an active, known or suspected autoimmune disease other than those listed below. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• •Patients are excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 12 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 12 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intraarticular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).
• •Physiologic replacement doses of systemic corticosteroids are permitted, even if \> 12 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• •Patients are excluded if they have previously received anti-CTLA-4 therapy. Prior anti- PD-1 or anti-PD-L1 therapy is permitted with 6-month washout period unless the following treatment-related toxicities are present:
• •* Any toxicity NCI CTCAE grade \>/= 3 from previous immunotherapy that did not resolve to grade 1 with or without immunosuppressive therapy. Patients must be off all immunosuppressive therapy prior to enrollment.
• •* Myocarditis, any grade.
• •* Pneumonitis, any grade.
• •* Patients with grade 2 hepatitis or colitis will be evaluated on a case-by-case basis and may be included only after consultation with a Gastroenterologist and the study physician.
• •Has a known history of active TB (Bacillus Tuberculosis).
• •No active or chronic HBV or HCV. Patients are excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. Subjects with a history of HBV or HCV require documentation of treatment completion, further testing is not required.
• •Patients are excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• •These participants are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •Is 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 5 months for woman and 7 months for men, after the last dose of trial treatment.
• •Has a known additional malignancy that is progressing or requires active treatment.
• •Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• •Has known history of, or any evidence of active, non-infectious pneumonitis.
• •Has an active infection requiring systemic therapy.
• •Has received a live/attenuated 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®) are live attenuated vaccines, and are not allowed.
• •History of allergy to study drug components.
• •History of severe hypersensitivity reaction to any monoclonal antibody.
• •Uncontrolled brain metastases. Patients treated with radiation \> 4 weeks prior with follow up imaging showing control are eligible