669P - TG01/GM-CSF and adjuvant gemcitabine in patients with resected RAS-mutant adenocarcinoma of the pancreas.

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cytotoxic agents
Pancreatic Cancer
Gastrointestinal Cancers
Therapy
Biological therapy
Presenter Svein Dueland
Citation Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369
Authors S. Dueland1, J.W. Valle2, K. Bell3, O. Faluyi4, H. Staiger2, T.J. Gjertsen5, A. Møller5, A. Aksnes5, D. Palmer6
  • 1Department Of Clinical Cancer Research, Oslo University Hospital and Norwegian Radium Hospital, 0310 - Oslo/NO
  • 2Clinical Oncology, The Christie NHS Foundation Trust, Manchester/GB
  • 3Department Of Clinical Cancer Research, Oslo University Hospital and Norwegian Radium Hospital, Oslo/NO
  • 4Department Of Molecular And Clinical Cancer Medicine, University of Liverpool, L69 3GA - Liverpool/GB
  • 5Clinical, Targovax ASA, Oslo/NO
  • 6Department Of Molecular And Clinical Cancer Medicine, University of Liverpool, Liverpool/GB

Abstract

Background

The study evaluated the immune response, safety and clinical efficacy of the TG01/GM-CSF vaccine, an antigen-specific cancer immunotherapy consisting of 7 RAS peptides targeted to KRAS mutated pancreatic adenocarcinoma (PAC). The efficacy of adjuvant chemotherapy in resected disease is limited 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.

Methods

Patients (pts) were eligible after R0 or R1 PAC 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-CSF was 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 and T-cell proliferation. OS and disease free survival (DFS) was assessed from surgery; ∼8 weeks before first TG01 injection.

Results

To date, 19 pts (68% R1) have been followed for 2 1/2 yrs. Median CA19-9 was 15 (5, 240) U/ml at baseline. 8 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 were no treatment related deaths. TG01 induce an immune response in 17/19 patients by week 11, which demonstrate that TG01 vaccination activate TG01 specific T-cells. OS rate at 2 yrs was 68.4 (95% CI 47.5, 89.3). OS rate at 2 1/2 yrs will be presented. Median OS was 33.1 months (95% CI 16.8, 40.1). Median DFS was 13.9 months (95% CI 5.4-21.0).

Conclusions

The regimen was generally well tolerated although some late, manageable allergic reactions were seen. OS and DFS was encouraging in view of published reports. TG01/GM-CSF generated early immune responses in 89% of patients with R0/R1 resected pancreatic cancer. 13 pts have been recruited in a modified dose cohort with 2 yrs data in 2Q 2018.

Clinical trial identification

NCT02261714.

Legal entity responsible for the study

Targovax ASA

Funding

Targovax ASA

Disclosure

T.J. Gjertsen, A-S. Møller: Share options in Targovax ASA. A-K. Aksnes: Stocks and share options in Targovax ASA. D. Palmer: Honoraria: Celgene, Nucana, Bayer, BMS. Consulting and advisory role: Celgene, Nucana, Bayer, BMS Research funding: Nucana, Bayer. All other authors have declared no conflicts of interest.