No accrual

The purpose of this study is to find out whether temozolomide followed by nivolumab is an effective treatment for MMR-proficient colorectal cancer, while causing few or mild side effects.

Inclusion Criteria:

• Subject or legally authorized representative, is willing and able to provide written informed consent/assent for the trial
• Histologically- or cytologically- confirmed CRC
• Locally advanced or metastatic CRC
• Confirmation of MGMT promoter methylation on archived tissue by PCR analysis (any time).
• MGMT promoter methylation is determined using the ARUP laboratory assay (or similar). Total methylation is calculated as an average across listed CpG sites. Total methylation of 0-9 percent is reported as "Not detected" 10-29 percent as "Low level" and equal or more than 30 percent as "Detected". Patients will require MGMT promoter methylation to be "detected" in order to be eligible.
• Undergone testing for MSI/dMMR and determined to be MSS or MMR proficient
• Subjects must be refractory or intolerant to at least 2 lines of standard chemotherapy, according to NCCN guidelines for patients eligible for intensive therapy. At a minimum, such therapies should include regimens containing oxaliplatin or irinotecan in combination with a fluoropyrimidine (e.g., FOLFOX or FOLFIRI or their variants).
• At least one index lesion which is measurable based on RECIST 1.1
• Be >/= 18 years of age on day of signing informed consent
• Consent for tumor biopsies and blood draws for research purposes
• Have an ECOG performance status of 0 or 1
• Demonstrate adequate organ function as defined in Table 6.1, all screening labs should be performed within 28 days of treatment initiation.

Adequate Organ Function Laboratory Values

Hematological

• Absolute neutrophil count (ANC) >/= 1,500/mcl
• Platelets >/= 100,000/mcl
• WBC >/= 2000/ul
• Hemoglobin >/= 9.0 g/dL

Renal

• Serum creatinine </= 1.5 x upper limit of normal (ULN) OR
• Measured or calculated creatinine clearance (GFR can also be used in place of creatinine of CrCl) >/= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (Creatinine clearance should be calculated per institutional standard)

Hepatic

• Serum total bilirubin </= 1.5 x ULN -OR- Direct bilirubin </= ULN for subjects with total bilirubin levels > 1.5 ULN
• AST (SGOT) and ALT (SGPT) </= 2.5 x ULN -OR- </= 5 x ULN for subjects with liver metastases
• Female subject of childbearing potential should have a negative serum pregnancy within 2 weeks prior to starting treatment
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy (defined in section 7.1). In addition, male subjects must be willing to refrain from sperm donation during this time.

Coagulation

• International Normalized Ratio (INR) or Prothrombin Time (PT) </= 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
• 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

Exclusion Criteria:

• Subject is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (>10 mg/day prednisone, or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. inhaled or topical steroids are permitted in the absence of active autoimmune disease
• Prior chemotherapy, targeted small molecule therapy, or biological therapy, within 2 weeks prior to study Day 1 or who has not recovered (i.e., \

Here is the final approved MSK data sharing statement for posting on any trial opened 1/1/19 or later -

• Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.