Inclusion Criteria:

• Male and female adult patients (≥ 18 years of age on day of signing informed consent) with a histologically confirmed advanced, metastatic, or progressive CRC that is MSS. Microsatellite stability is based on prior polymerase chain reaction (PCR), Next-Gen sequencing, or immunohistochemistry results per institutional standards.
• Patient has received at least two prior lines of therapy for advanced or metastatic CRC, at least one of which included fluorouracil. Adjuvant therapy will be counted as a line of therapy only if progression occurs within 6 months of its completion.
  • Note: there is no limit to the number of prior treatment regimens.
• Have measurable disease per RECIST v1.1 as assessed by the local site investigator/ radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Accessible tumor that can be safely accessed for multiple core biopsies and patient is willing to provide tissue from newly obtain biopsies before and during treatment.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have adequate organ function as follows:
  • Note: Screening specimens must be collected within 7 days prior to entering the Treatment period.
  • Absolute neutrophil count (ANC) ≥ 1500/µL; 
  • Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L;
  • Note: Criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within last 2 weeks;
  • Platelet count ≥ 75,000/µL;
  • Serum creatinine ≤1.5 × upper limit of normal (ULN) or creatinine clearance ≥ 40 mL/min for patients with creatinine levels >1.5 × institutional ULN (using the Cockcroft-Gault formula);
  • Serum sodium (Na) and potassium (K) within normal limits;
  • Serum total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 × ULN. Known Gilbert syndrome is allowed if total bilirubin is <3 × ULN;
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (or higher if liver metastases are present and approved by Sponsor);
  • Coagulation: INR or PT and aPTT ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
• Willing to use contraception for women who are not postmenopausal and all men.
• Be willing and able to provide written informed consent for the trial.

Exclusion Criteria:

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
• Current use of NSAIDs (e.g., ibuprophen, naproxen), COX-2 inhibitors (e.g., celecoxib), and Aspirin products within 3 days (and preferably 7 days) before treatment initiation or at any time during the study unless used for management of AE or otherwise authorized by the Sponsor. Aspirin products should be limited to prophylactic cardiovascular doses unless discussed with the Sponsor.
• History of severe hypersensitivity reactions to chimeric or humanized antibodies.
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to treatment, or 5 half-lives, whichever is shorter.
  • Note: Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible after discussion with the Sponsor.
  • Note: If participant received major surgery, they must have fully recovered from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
  • Note: No other concurrent antineoplastic treatment is permitted on study except for allowed local radiation of lesions for palliation only (to be considered non-target lesions after treatment).
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Participants taking strong CYP3A4 or P-glycoprotein inhibitors or inducers are excluded from the study unless they can be transferred to other medications within ≥ 5 half-lives prior to dosing.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
• Has a known additional potentially life-threatening malignancy that is progressing or has required active treatment within the past 3 years.
  • Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable; i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), and/or clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, 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) is not considered a form of systemic treatment and is allowed. Autoimmune diseases include but are not limited to inflammatory bowel disease (IBD) such as Crohn’s disease and ulcerative colitis.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Recent (within the last 12 months) or current GI ulcer or non-immune colitis.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known history of Hepatitis B or known active Hepatitis C virus infection.
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or uncontrolled cardiac arrhythmia.
• Has had an allogeneic tissue/solid organ transplant.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study.
• A woman of childbearing potential (WOCBP) who has a positive pregnancy test prior to treatment.
• Is breastfeeding or expecting to conceive or father children within the projected duration of the study.