• Vaccinations
• Gastrointestinal Cancers Clinical Trials

• Oncology
• Vaccinations
• Gastrointestinal Cancers
• Oncology Clinical Trials

Sequential or concurrent treatment with the vaccine GV100 with chemotherapy does not result in a survival advantage in patients with advanced pancreatic cancer. Gary W. Middleton, MD, University of Birmingham, Birmingham, United Kingdom, presented data from the fourth interim analysis of the Gemcitabine and Capecitabine With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer study [TeloVac; NCT00425360; Middleton GW et al. J Clin Oncol 2013 (suppl; abstr LBA4004)].

Reactivation of the telomerase enzyme is a common mechanism by which cancer cells prevent their senescence and ∼80% of pancreatic cancers overexpress telomerase. The GV1001 vaccine targets the hTERT subunit of telomerase that is expressed on the surface of pancreatic cancer cells. In addition, gemcitabine (GEM) has been demonstrated to have immune priming effects that are dependent on the dosing schedule [Nowak AK et al. Cancer Res 2003]. The hypothesis of the TeloVac study was that the addition of GV1001 to the current standard of care for advanced pancreatic cancer would provide an overall survival (OS) advantage.

In the multicenter, Phase 3 TeloVac trial, 1062 patients with advanced pancreatic cancer and an ECOG PS of 0 to 2 were randomized 1:1:1 to receive GEM plus capecitabine (CAP); GEM plus CAP followed by GV1001 followed by additional chemotherapy if disease had not progressed by Week 8; and concurrent administration of GEM, CAP, and GV1001.

The median follow-up was 6.11 months and 72.7% of patients died during the study. The primary endpoint was OS. Overall response rate (ORR), time to progression (TTP), and adverse events were secondary endpoints. Prof. Middleton commented that the TeloVac trial was closed following the fourth interim analysis due to declaration of futility.

Administration of GV1001 did not provide a significant benefit when given concurrently or sequentially following GEM and CAP therapy. OS in the sequential GV1001 arm was statistically nonsignificantly inferior at 6.94 months with a 12-month survival rate of 25.3% (HR, 1.19; 95% CI, 0.97 to 1.48; p=0.0466), compared with 7.89 months and 33.7% in the GEM plus CAP arm and 8.36 months and 32.3% in the concurrent arm (HR, 1.05; 95% CI, 0.85 to 1.29; p=0.6378). The ORR was 17.6% in the GEM plus CAP arm (referent), 8.6% in the GEM plus CAP with sequential GV1001 arm (p=0.001), and 15.5% in the concurrent GEM, CAP, and GV1001 arm (p=0.536).

Sequential GV1001 therapy also resulted in a significant inferiority in TTP compared with the other two arms (HR, 1.50; 95% CI, 1.26 to 1.78; p<0.001). The frequency of hematologic and nonhematologic adverse events was similar among each of the treatment arms.

Although GV1001 was well tolerated, it did not appear to provide a benefit in regard to OS, TTP, or ORR. Prof. Middleton pointed out that in the GV1001 sequential arm, progression rates began to increase as soon as patients discontinued chemotherapy for GV1001 treatment, although this did not translate into a significant difference. Immunological analyses, including for predictive biomarkers, are currently ongoing.

• © 2013 MD Conference Express®