Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors

Inclusion Criteria:

- Subjects must have signed and dated an IRB-approved written informed consent form
prior to the performance of any protocol-related procedures that are not part of
standard care.

- Colorectal or appendiceal mucinous adenocarcinoma with peritoneal-only metastatic
disease. It is recognized that in some patients, peritoneal disease will predominate
without distinction of the site of origin, and such patients will be eligible.

- Microsatellite stable by PCR and/or mismatch repair proficient by immunohistochemistry

- ECOG performance status of 0 or 1

- Prior therapy with a fluoropyrimidine, oxaliplatin, and irinotecan unless
contraindicated or refused. Prior treatment with antiangiogenic and/or anti-EGFR
antibody therapy is permitted but not required

- Measurable disease by RECIST v. 1.1

- Laboratory parameters:

- Absolute neutrophil count > 1500/μL

- Platelets > 100,000/μL

- Hemoglobin > 9.0 g/dL

- PT/INR or PTT < 1.5xULN

- Creatinine < 1.5xULN OR creatinine clearance > 50 mL/min by Cockcroft-Gault
formula

- Total bilirubin < 1.5xULN

- Subjects with Gilbert's Syndrome must have a total bilirubin level of < 3.0xULN

- Albumin > 3.0 g/dL

- AST and/or ALT: < 3.0×ULN

- Subjects with HIV are permitted provided they meet the following criteria:

- CD4+ cell count > 250 cells/mm3

- No history of AIDS-defining conditions other than low CD4+ count

- If subject is on antiretroviral therapy, there must not be expected significant
drug-drug interactions with study treatment

Exclusion Criteria:

- Bowel obstruction within the past 60 days

- Subjects who are currently pregnant, planning to become pregnant, or breast-feeding.

- Females participants of child-bearing potential are required to use an effective
contraception method or abstain from intercourse during treatment and for at
least 5 months following the last dose

- Males participants with partners of child-bearing potential are required to use
an effective contraception method or abstain from intercourse during treatment
and for at least 7 months following the last dose

- Subjects who, in the opinion of the physician, would not be clinically appropriate for
receipt of the therapy regimen associated with participation

- Subjects with contraindications to immune checkpoint therapy, as follows:

- Interstitial lung disease that is symptomatic or may interfere with the detection
and management of suspected drug-related pulmonary toxicity

- Prior organ allograft or allogeneic bone marrow transplantation

- Pre-existing thyroid abnormality with thyroid function that cannot be maintained
in the normal range with medication

- Active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma,
atopic dermatitis, or endocrinopathies manageable by hormone replacement; other
autoimmune conditions may be allowable at the discretion of the principal
investigator

- Condition requiring systemic treatment with corticosteroids

- Systemic steroids at physiologic doses (equivalent to dose of oral
prednisone 10 mg) are permitted.

- Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids
with minimal systemic absorption are permitted.

- Established non-peritoneal metastatic disease, including but not limited to metastases
to the liver, lung, brain, extra-abdominal lymph nodes, and bone

- A second primary malignancy that, in the judgment of the investigator, may affect
interpretation of results

- Prior treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody

- Toxicities attributed to prior anti-cancer therapy other than alopecia, fatigue, and
peripheral neuropathy must have resolved to Grade 1 or baseline before administration
of study drug. In addition, a washout period will be required for prior therapies as
specified:

- No chemotherapy within 14 days prior to first dose

- No investigational product(s) (IPs) and/or biologic therapy within 28 days or 5
half-lives, whichever is longer, prior to first dose

- No major surgery within 28 days prior to first dose. Any surgery-related AE(s)
must have resolved at least 14 days prior to first dose.

- No radiation therapy with curative intent within 28 days prior to first dose.
Prior focal palliative radiotherapy must have been completed at least 14 days
prior to first dose.

- Active hepatitis B or hepatitis C, defined as the following:

- Hepatitis B surface antigen positive or HBV DNA PCR >100 IU/mL

- Hepatitis C antibody positive unless HCV RNA PCR is negative (i.e. undetectable
viral load)

- Prisoners or participants who are involuntarily incarcerated. (Note: under specific
circumstances a person who has been imprisoned may be included as a participant.
Strict conditions apply and BMS approval is required.)

- Participants who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness