Telomerase-based GX301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase II trial.

Debate is around the optimal immunization regimen for cancer vaccines since too intense vaccination schedules may exhaust reactive lymphocytes. GX301 is a telomerase-based cancer vaccine whose safety and immunological effects were tested in a phase I trial applying an eight administrations schedule. Main objective of this study was to comparatively analyse safety and immunological response to three GX301 regimens in metastatic castration-resistant prostate cancer patients with response/disease stability after docetaxel chemotherapy. This was a multicentre, randomized, parallel-group, open-label trial registered with EudraCT (2014-000095-26) and ClinicalTrials.gov (NCT02293707, 2014). Ninety-eight patients were randomized to receive either eight (regimen 1), four (regimen 2) or two (regimen 3) vaccine administrations. Sixty-three patients were assessable for the primary immunological end-point. Vaccine-specific immune responses were evaluated by intracellular staining for IFN, elispot and cytotoxic assay at 90 and 180 days from baseline. No major side effects were recorded. A 54% overall immune responder rate was observed with 95% of patients showing at least one vaccine-specific immune response. Rate of immunological responders and number of immunizations were proportionally related, suggesting superiority of regimens 1 and 2 over regimen 3. Overall survival did not differ among regimens in both immunological responders and non-responders and was inversely associated (P = 0.002) with increase in the number of circulating CD8 + T regulatory cells at 180 days. These data indicate that GX301 cancer vaccine is safe and immunogenic in metastatic castration-resistant prostate cancer patients. Schedules with high number of administrations should be preferred in future studies due to their better immunological outcome.

Postgraduate Courses in Pharmaceutical Medicine in Italy.

Italy has a significant tradition of excellence in the area of clinical trials (CTRs): important achievements in the clinical development of rifampicin and adriamycin, the two most famous drugs discovered in the research laboratories of two Italian pharmaceutical companies, paved the way to the establishment of a culture of clinical development, mainly in the areas of antimicrobials and oncology. Despite the fact that now the Italian market of pharmaceuticals is largely dominated by multinational companies with headquarters outside Italy, the contribution of Italian studies to the clinical development of new drugs is still significant. Indeed, it largely exceeds the percentage of Italian inhabitants versus the ones living in the remaining EU countries, as Italy has about 12% of EU population, but has a 17% share of the EU CTRs. Education in Pharmaceutical Medicine is now a must for all professionals interested to work either in pharma companies or in contract research organizations: several Italian universities are offering high quality courses, and in the last 10 years, more than 1,200 professionals received a postgraduate education in pharmaceutical medicine. This result places Italy on top of countries concerned about the professional education of people involved in drug development and will represent an asset for a larger involvement of Italian clinical sites in the global process of clinical research.

A multi-peptide, dual-adjuvant telomerase vaccine (GX301) is highly immunogenic in patients with prostate and renal cancer.

BACKGROUND: Anti-tumor vaccination is a new frontier in cancer treatment applicable to immunogenic neoplasms such as prostate and renal cancers. GX301 is a vaccine constituted by four telomerase peptides and two adjuvants, Montanide ISA-51 and Imiquimod. OBJECTIVE: The aim of this study was to analyze safety and tolerability of GX301 in an open-label, phase I/II trial. Immunological and clinical responses were also evaluated as secondary endpoints. EXPERIMENTAL DESIGN: GX301 was administered by intradermally injecting 500 µg of each peptide (dissolved in Montanide ISA-51) in the skin of the abdomen. Imiquimod was applied as a cream at the injection sites. The protocol included 8 administrations at days 1, 3, 5, 7, 14, 21, 35, 63. Eligible patients were affected with stage IV prostate or renal cancer resistant to conventional treatments. Patients were clinically and immunologically monitored up to 6 months from the first immunization. RESULTS: No grade 3-4 adverse events were observed. Evidence of vaccine-specific immunological responses was detected in 100 % of patients. Disease stabilization occurred in 4 patients. Prolonged progression-free survival and overall survival were observed in patients showing a full pattern of vaccine-specific immunological responses. CONCLUSION: GX301 demonstrated to be safe and highly immunogenic. Further studies are needed to determine its clinical efficacy.