A phase I/II trial of TG01/GM-CSF and gemcitabine as adjuvant therapy for treating patients with resected RAS-mutant adenocarcinoma of the pancreas.
Abstract
4119 Background: TG01 (a mixture of 7 RAS peptides) is an injectable antigen-specific cancer immunotherapy targeted to treat patients (Pts) with KRAS mutations, found in more than 85% of pancreatic adenocarcinomas. There is scope for improvement in adjuvant treatment of resected pancreatic cancer; with 1- and 2-year published overall survival (OS) rates ranging from 56-80% and 30-54% respectively. TG01 induces RAS mutant-specific T-cell responses which are enhanced by co-administration of GM-CSF. This study evaluates safety, immunological response and OS of TG01-immunotherapy with adjuvant gemcitabine chemotherapy. Methods: Pts were eligible after an R0 or R1 pancreatic adenocarcinoma resection. As soon as possible after surgery, TG01 (0.7 mg intradermal injection (id)) together with GM-CSF (0.03 mg id) was given on days 1, 3, 5, 8, 15, 22 and 2-weekly thereafter until the end of gemcitabine (starting within 12 weeks of surgery and given for 6 cycles). Thereafter TG01/GM-CFS were given 4-weekly up to 1 yr and 12-weekly up to 2 yrs. Immune response was assessed using antigen-specific (TG01) Delayed-Type Hypersensitivity (DTH) and T-cell proliferation. OS was assessed from surgery; ~8 weeks before first TG01 injection. Results: To date, 19 pts (68% R1) from 3 sites (Norway and UK) and have been followed for 2 yrs.Eight SARs in 5 pts have occurred; 4 related to gemcitabine (anemia, pulmonary infection and 2 fever); 3 related to TG01/GM-CSF (2 anaphylaxes and 1 hypersensitivity); and 1 possibly related to all products (dyspnea). The allergic reactions only occurred after several cycles of gemcitabine and resolved within 1-2 hrs. There was no treatment related deaths.16/19 (84%) pts had a positive DTH by week 11. Proliferation of mutant RAS specific T-cells is being analyzed. OS rate at 1 and 2 yrs were 89.5% (95% CI 75.7, 100.0) and 68.4 (95% CI 47.5, 89.3), respectively. Median OS was 33.1 months (95% CI 16.8, 40.1). Conclusions: TG01/GM-CSF generated early immune responses in 84% of patients with R0/R1 resected pancreatic cancer. The regimen was generally well tolerated although some late, manageable allergic reactions were seen. OS was encouraging in view of published reports. Clinical trial information: NCT02261714.
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Palmer et al. reported a phase I/II trial in which a mixture of seven RAS peptides, TG01, induced RAS mutant-specific T-cell responses that could be enhanced by co-administration of GM-CSF in patients with resected RAS-mutant adenocarcinoma of the pancreas.
“In 2017, Palmer et al. reported the results of a phase I/II trial (NCT02261714) conducted by Targovax ASA, which demonstrated that a mixture of seven RAS peptides, called TG01 (256), could induce RAS mutant-specific T-cell responses that could be enhanced by co-administration of GM-CSF in patients with resected RAS-mutant adenocarcinoma of the pancreas.600”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [600]
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- Authors
- Palmer, D. H., Dueland, S., Valle, J. W., & Aksnes, A.-K.
- Affiliations
- University of Liverpool (GB)
- Oslo University Hospital (NO)
- The Christie NHS Foundation Trust (GB)
- Targovax (Norway) (NO)
- Venue
- Journal of Clinical Oncology
- Published
- 2017-05-20
- Volume
- 35
- Issue
- 15_suppl
- Pages
- 4119-4119
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2889639085
- Cited by
- 12
- References
- 0
- Citations by year
- 2023: 1 · 2020: 3 · 2019: 4 · 2018: 4
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- GM-CSF, gemcitabine, adjuvant therapy, pancreatic ductal adenocarcinoma, KRAS mutation, delayed-type hypersensitivity, T cell proliferation, overall survival, safety, resected pancreatic cancer, R1 resection margin, anaphylaxis, immunotherapy toxicity, T cell response
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