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
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...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024173951 |
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| author | Sara Roth Kasmira Claire Wilson Robert George Ramsay Catherine Mitchell Shienny Sampurno Toan Duc Pham Joseph Cherng Huei Kong Stephen Q. Wong Alexander Graham Heriot Sanjeev Deva Matthew Burge Cecilie Sverdrup Anne-Sophie Moller Lukasz Kuryk Jon Amund Eriksen Magnus Jaderberg John Raymond Zalcberg Michael Michael |
| author_facet | Sara Roth Kasmira Claire Wilson Robert George Ramsay Catherine Mitchell Shienny Sampurno Toan Duc Pham Joseph Cherng Huei Kong Stephen Q. Wong Alexander Graham Heriot Sanjeev Deva Matthew Burge Cecilie Sverdrup Anne-Sophie Moller Lukasz Kuryk Jon Amund Eriksen Magnus Jaderberg John Raymond Zalcberg Michael Michael |
| author_sort | Sara Roth |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c94a54eed56f4278858edf2f9ebb5f0c |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-c94a54eed56f4278858edf2f9ebb5f0c2025-01-17T04:51:03ZengElsevierHeliyon2405-84402025-01-01111e41364A non-randomised open-label exploratory ‘window of opportunity’ study of TG02 treatment in patients with locally advanced primary and recurrent RAS mutant colorectal cancerSara Roth0Kasmira Claire Wilson1Robert George Ramsay2Catherine Mitchell3Shienny Sampurno4Toan Duc Pham5Joseph Cherng Huei Kong6Stephen Q. Wong7Alexander Graham Heriot8Sanjeev Deva9Matthew Burge10Cecilie Sverdrup11Anne-Sophie Moller12Lukasz Kuryk13Jon Amund Eriksen14Magnus Jaderberg15John Raymond Zalcberg16Michael Michael17Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Australia; Monash University Department of Surgery, Alfred Hospital, Melbourne, AustraliaSir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, AustraliaSir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, AustraliaSir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, AustraliaDivision of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, AustraliaSir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, AustraliaSir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Australia; Monash University Department of Surgery, Alfred Hospital, Melbourne, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, AustraliaSir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, AustraliaSir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, AustraliaDepartment of Medical Oncology, Auckland City Hospital, Auckland, New ZealandDepartment of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Australia; University of Queensland, St Lucia, Brisbane, AustraliaTargovax ASA, Oslo, NorwayTargovax ASA, Oslo, NorwayTargovax ASA, Oslo, NorwayTargovax ASA, Oslo, NorwayTargovax ASA, Oslo, NorwayDepartment of Medical Oncology, Alfred Health & School of Public Health, Faculty of Medicine, Monash University, Melbourne, AustraliaSir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Corresponding author. Medical Oncologist Lower & Upper GI Oncology Service, Neuroendocrine Unit, an ENETS Centre of Excellence Peter MacCallum Cancer Centre 305 Grattan Street, Melbourne, VIC, 3000, Australia.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.http://www.sciencedirect.com/science/article/pii/S2405844024173951Colorectal cancerCancer vaccineKRASTG02GM-CSF |
| spellingShingle | Sara Roth Kasmira Claire Wilson Robert George Ramsay Catherine Mitchell Shienny Sampurno Toan Duc Pham Joseph Cherng Huei Kong Stephen Q. Wong Alexander Graham Heriot Sanjeev Deva Matthew Burge Cecilie Sverdrup Anne-Sophie Moller Lukasz Kuryk Jon Amund Eriksen Magnus Jaderberg John Raymond Zalcberg Michael Michael 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 Heliyon Colorectal cancer Cancer vaccine KRAS TG02 GM-CSF |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | non randomised open label exploratory window of opportunity study of tg02 treatment in patients with locally advanced primary and recurrent ras mutant colorectal cancer |
| topic | Colorectal cancer Cancer vaccine KRAS TG02 GM-CSF |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024173951 |
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