A non-randomised open-label exploratory 'window of opportunity' study of TG02 treatment in patients with locally advanced primary and recurrent mutant colorectal cancer.

Background: TG02 is a peptide-based cancer vaccine eliciting immune responses to oncogenic codon 12/13 mutations. This phase 1 clinical trial (NCT02933944) assessed the safety and immunological efficacy of TG02 adjuvanted by GM-CSF in patients with -mutant colorectal cancer.

Methods: In the interval between completing CRT and pelvic exenteration, patients with resectable mutation-positive, locally advanced primary or current colorectal cancer, received 5-6 doses of TG02/GM-CSF. Immune response was defined as a positive delayed-type hypersensitivity or positive T cell proliferation assay response. Tumour biopsies were analysed for tumour-infiltrating lymphocytes (TILs) and blood for CEA and ctDNA. TILs and tumouroids were cultured, characterised and tested for their killing efficacy.

Results: Six patients with rectal cancer were recruited to evaluate TG02. Three patients experienced a total of 16 treatment-related adverse events; all grade 1. Four of the 6 patients (66.7 %) had at least one vaccine-induced TG02 immune response. Flow cytometry analysis showed high proportion of PD-1-expressing TILs in 2 of 3 patient specimens' post-treatment. A partial to near complete pathological response was reported in 4 of 6 patients.

Conclusions: This study demonstrated that TG02/GM-CSF was well tolerated and induced a vaccine specific systemic immune response in the majority of patients. Low numbers limit conclusive clinical outcome reporting. High PD-1 expression on post-treatment TILs encourages the addition of an immune checkpoint inhibitor to TG02 and potentially other studies of peptide vaccines in future studies.