Neo-adjuvant Pembrolizumab and Radiotherapy in Localised MSS Rectal Cancer

Inclusion Criteria: * Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of rectal adenocarcinoma will be enrolled in this study. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation. * Patients with previously untreated localized T3-T4 N0 or T any or N1-2, M0 rectal adenocarcinoma. * Tumour must be microsatellite stable (MSS). * A multi-disciplinary tumour board should recommend neo-adjuvant short course radiotherapy and surgery. * Have provided archival tumour tissue sample or newly obtained core or excisional biopsy of a tumour lesion not previously irradiated. Formalin-fixed paraffin embedded (FFPE) tissue blocks are preferred. * Have adequate organ function as defined in the following table. Specimens must be collected within 10 days prior to the start of study treatment. Exclusion Criteria: * Has a microsatellite instable tumour (MSI-High). * 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 (eg, CTLA-4, OX 40, CD137). * Has received for the same disease prior systemic anti-cancer therapy including investigational agents prior to starting pembrolizumab. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. * Has received prior radiotherapy for the same disease. If treated with radiotherapy for another disease, participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. * Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. * 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 to the first dose of study drug. * Has a known additional 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), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. * Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has an active infection requiring systemic therapy. * Has a known history of Human Immunodeficiency Virus (HIV). * Has a known history of Hepatitis B virus (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \> 1.5E1 is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. * Has a known history of active TB (Bacillus Tuberculosis). * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.