BACKGROUND: We aimed to assess the efficacy and safety of sequential or 
simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in 
patients with locally advanced or metastatic pancreatic cancer.
METHODS: TeloVac was a three-group, open-label, randomised phase 3 trial. We 
recruited patients from 51 UK hospitals. Eligible patients were treatment naive, 
aged older than 18 years, with locally advanced or metastatic pancreatic ductal 
adenocarcinoma, and Eastern Cooperative Oncology Group performance status of 
0-2. Patients were randomly assigned (1:1:1) to receive either chemotherapy 
alone, chemotherapy with sequential GV1001 (sequential chemoimmunotherapy), or 
chemotherapy with concurrent GV1001 (concurrent chemoimmunotherapy). Treatments 
were allocated with equal probability by means of computer-generated random 
permuted blocks of sizes 3 and 6 in equal proportion. Chemotherapy included six 
cycles of gemcitabine (1000 mg/m(2), 30 min intravenous infusion, at days 1, 8, 
and 15) and capecitabine (830 mg/m(2) orally twice daily for 21 days, repeated 
every 28 days). Sequential chemoimmunotherapy included two cycles of combination 
chemotherapy, then an intradermal lower abdominal injection of 
granulocyte-macrophage colony-stimulating factor (GM-CSF; 75 μg) and GV1001 
(0·56 mg; days 1, 3, and 5, once on weeks 2-4, and six monthly thereafter). 
Concurrent chemoimmunotherapy included giving GV1001 from the start of 
chemotherapy with GM-CSF as an adjuvant. The primary endpoint was overall 
survival; analysis was by intention to treat. This study is registered as an 
International Standard Randomised Controlled Trial, number ISRCTN4382138.
FINDINGS: The first patient was randomly assigned to treatment on March 29, 
2007, and the trial was terminated on March 27, 2011. Of 1572 patients screened, 
1062 were randomly assigned to treatment (358 patients were allocated to the 
chemotherapy group, 350 to the sequential chemoimmunotherapy group, and 354 to 
the concurrent chemoimmunotherapy group). We recorded 772 deaths; the 290 
patients still alive were followed up for a median of 6·0 months (IQR 2·4-12·2). 
Median overall survival was not significantly different in the chemotherapy 
group than in the sequential chemoimmunotherapy group (7·9 months [95% CI 
7·1-8·8] vs 6·9 months [6·4-7·6]; hazard ratio [HR] 1·19, 98·25% CI 0·97-1·48, 
p=0·05), or in the concurrent chemoimmunotherapy group (8·4 months [95% CI 
7·3-9·7], HR 1·05, 98·25% CI 0·85-1·29, p=0·64; overall log-rank of χ(2)2df=4·3; 
p=0·11). The commonest grade 3-4 toxic effects were neutropenia (68 [19%] 
patients in the chemotherapy group, 58 [17%] patients in the sequential 
chemoimmunotherapy group, and 79 [22%] patients in the concurrent 
chemoimmunotherapy group; fatigue (27 [8%] in the chemotherapy group, 35 [10%] 
in the sequential chemoimmunotherapy group, and 44 [12%] in the concurrent 
chemoimmunotherapy group); and pain (34 [9%] patients in the chemotherapy group, 
39 [11%] in the sequential chemoimmunotherapy group, and 41 [12%] in the 
concurrent chemoimmunotherapy group).
INTERPRETATION: Adding GV1001 vaccination to chemotherapy did not improve 
overall survival. New strategies to enhance the immune response effect of 
telomerase vaccination during chemotherapy are required for clinical efficacy.
FUNDING: Cancer Research UK and KAEL-GemVax.