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.
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.
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).
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
Legal entity responsible for the study
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.