Phase 1b/II Trial of Pembrolizumab Plus IMRT in Stage III/IV Carcinoma of Anus

CORINTH is a multi center trial with a single arm. Patients will be recruited into 3 successive cohorts followed by an expansion of the final cohort. For each cohort the first dose of Pembrolizumab will be given at an earlier time point during the chemo-radiation (CRT). Pembrolizumab will be given as an IV infusion every 21 days, and a total of 8 infusions per patient at 200mg per infusion. The first dose of pembrolizumab will be given at the following times: COHORT 1: beginning at Week 5 day 1 of CRT schedule COHORT 2: beginning at Week 3 day 1 of CRT schedule COHORT 3: beginning at Week 1 day 1 of CRT schedule\*\* Cohort 2 will be dependent on a Safety Review Committee (SRC) recommendation. If the SRC are concerned about toxicity in Cohort 1 but not sufficiently to stop the study, they are able to recommend that Cohort 2 can change to commence pembrolizumab at week 4. If the SRC are concerned about toxicity in Cohort 2 but not sufficiently to stop the study, they are able to recommend that Cohort 3 can change to commence pembrolizumab at week 2. Potential participants will be under the care of a consultant who specializes in the treatment of anal cancer and the patient will have been identified as requiring CRT treatment for their anal cancer. They will be assessed for eligibility before being consented and allocated to the current cohort. # Patients will be monitored for Adverse Events which will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) 4.03. Treatment guidelines are given for any immune related or infusion related events. Adverse Event review will take place weekly during CRT and at every pembrolizumab visit as well as key time during follow up. Patient reported outcomes will be assessed using the European Organisation for Research and Treatment of Cancer (EORTC) tool during CRT, pembrolizumab treatment and follow up. Patients will be followed up for 12 months.