A non-randomised open-label exploratory &#39;window of opportunity&#39; study of TG02 treatment in patients with locally advanced primary and recurrent RAS mutant colorectal cancer

Roth, S; Wilson, KC; Ramsay, RG; Mitchell, C; Sampurno, S; Pham, TD; Huei Kong, JC; Wong, SQ; Heriot, AG; Deva, S; Burge, M; Sverdrup, C; Moller, AS; Kuryk, L; Eriksen, JA; Jaderberg, M; Zalcberg, JR; Michael, M

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

Author(s): Roth, S; Wilson, KC; Ramsay, RG; Mitchell, C; Sampurno, S; Pham, TD; Huei Kong, JC; Wong, SQ; Heriot, AG; Deva, S; Burge, M; Sverdrup, C; Moller, AS; Kuryk, L; Eriksen, JA; Jaderberg, M; Zalcberg, JR; Michael, M;
Details: Publication Year 2025-01-15,Volume 11,Issue #1,Page e41364
Journal Title: Heliyon
Publication Type: Research article
Abstract: BACKGROUND: TG02 is a peptide-based cancer vaccine eliciting immune responses to oncogenic codon 12/13 RAS mutations. This phase 1 clinical trial (NCT02933944) assessed the safety and immunological efficacy of TG02 adjuvanted by GM-CSF in patients with KRAS-mutant colorectal cancer. METHODS: In the interval between completing CRT and pelvic exenteration, patients with resectable KRAS 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.
Publisher: Cell Press
Keywords: Cancer vaccine; Colorectal cancer; Gm-csf; Kras; Tg02
Department(s): Laboratory Research; Surgical Oncology; Pathology; Medical Oncology
Publisher's Version: https://doi.org/10.1016/j.heliyon.2024.e41364
Open Access at Publisher's Site: https://doi.org/10.1016/j.heliyon.2024.e41364
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-01-28 02:47:14

Last Modified: 2025-01-28 02:54:38