Pembrolizumab and Autologous Dendritic Cells for the Treatment of Refractory Colorectal Cancer (CRC)

Inclusion Criteria:

• Age >= 18 years of age

• Recurrent and/or metastatic unresectable microsatellite stable (MSS) colorectalcancer

• At least 2 target lesions present per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at least one of which is amenable to biopsy and injection

• Prior treatment with, contra-indication to, or refusal of a fluoropyrimidine,irinotecan, oxaliplatin and an anti-EGFR targeted therapy (if RAS wt), as well asavastin/bevacizumab

• PD-1/PD-L1/PD-L2 treatment naïve patients are eligible

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Platelet >= 75,000/uL

• Hemoglobin >= 8 g/dL (without transfusion in the past 14 days)

• Absolute neutrophil count (ANC) >= 1500/uL

• Estimated creatinine clearance (Cockcroft Gault) >= 30 mL/min/ for participant withcreatinine levels > 1.5 x institutional upper limit of normal (ULN)

• Total bilirubin: =< 2 x ULN OR direct bilirubin =< ULN for participants with totalbilirubin levels > 2 x ULN

• Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) andalanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) =< 3 xinstitutional ULN (=< 5 x ULN for participants with liver metastases)

• Women of childbearing potential must agree to use acceptable birth control methodsfor the duration of the study and until persistence of the study drug is no longerdetected in the peripheral blood: This may be a period of several years. Methods foracceptable birth control include condoms, diaphragm or cervical cap with spermicide,intrauterine device, and hormonal contraception; it is recommended that acombination of two methods be used

• NOTE: If the risk of conception exists, patients must continue to use highlyeffective contraception for at least two years following the last studytreatment administration

• A male participant must agree to use a contraception during the treatment period andfor at least 1 year after the last dose of study treatment and refrain from donatingsperm during this period

• Participant must understand the investigational nature of this study and sign anIndependent Ethics Committee/Institutional Review Board approved written informedconsent form prior to receiving any study related procedure

Exclusion Criteria:

• Patients currently treated with systemic immunosuppressive agents. If a patient iscurrently on steroids, they must be on a steroid dose less than or equal to anequivalent prednisone dose of 10 mg daily

• Patients with active autoimmune disease, requiring ongoing immunosuppressive therapyor history of transplantation

• Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis. Participants with previously treated brain metastases may participateprovided they are radiologically stable, i.e. without evidence of progression for atleast 4 weeks by repeat imaging (note that the repeat imaging should be performedduring study screening), clinically stable and without requirement of steroidtreatment for at least 14 days prior to first dose of study intervention

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent orwith an agent directed to another stimulatory or co-inhibitory T-cell receptor

• Has received prior chemotherapy or radiotherapy within 2 weeks of start of studyintervention. All chemotherapy or radiation-related toxicities must be resolved to =< grade 1, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) tonon-CNS disease

• Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks prior to the first doseof study intervention

• 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 ofimmunosuppressive therapy within 7 days prior to the first dose of study drug

• Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of itsexcipients

• Has a history of (non-infectious) pneumonitis/interstitial lung disease thatrequired steroids or has current pneumonitis/interstitial lung disease

• Has an active infection requiring systemic therapy

• Has a known history of human immunodeficiency virus (HIV) infection. Note: No HIVtesting is required

• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV]ribonucleic acid [RNA] [qualitative] is detected) infection. Note: no testing forhepatitis B and hepatitis C is required

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements

• Pregnant or nursing female participants

• Unwilling or unable to follow protocol requirements

• Any condition which in the investigator's opinion deems the participant anunsuitable candidate to receive study drug