Phase II clinical trial of mutant Ras peptide vaccine in combination with GM-CSF and IL-2 in advanced cancer patients

3067 Background: Mutant ras oncogenes produce novel proteins that are processed and displayed through HLA molecules on tumor cells. Therefore, mutant ras is an attractive target for vaccine therapy. We have shown in a previous phase I trial that vaccination with mutant ras peptides produced specific immune responses (IR). Here we tested in a phase II trial the use of specific mutant ras peptides in combination with GM-CSF and IL-2 in advanced cancer patients carrying the ras mutation in their tumors. Methods: We treated 17 patients with advanced cancers (14 CRC, 1 NSCLC and 2 pancreatic) with 5000μg of the corresponding mutant ras peptide given SQ along with GM-CSF and IL-2. GM-CSF was given SQ on days -1,0,1,2 followed by ten days of low dose SQ IL-2. Vaccines were repeated every 5 weeks for a maximum of 15 cycles or until disease progression. Results: 11 patients who received 3 or more vaccinations were tested for immune response by measuring IFN-γ mRNA copies in PBMCs pre and post vaccination. 6/11 patients generated specific IR to the corresponding mutant ras vaccine. The median overall survival and the median progression-free survival for all patients were 25.8 and 13.1 months respectively. However, in the 6 patients with positive IR, it was 39.9 and 17.9 months compared to 18.5 and 15.6 months in the 5 patients who showed no IR. No grade IV toxicity occurred. Most adverse events were Grade I-II toxicities and resolved spontaneously. Grade III toxicities led to IL-2 dose reduction in 3/17 patients (18%). Conclusions: The study showed that vaccination of advanced cancer patients with mutant ras peptides in combination with GM-CSF and IL-2 is safe and can induce specific immune responses. Furthermore, those patients who generated IR showed better clinical outcome, as reflected by PFS and OS. So we believe that this vaccine may form a potentially promising approach in combination with other therapeutic modalities in advanced solid tumors. No significant financial relationships to disclose.