A Randomized Phase Ii Study Of The Csf-470 Therapeutic Vaccine Plus Bcg Plus Rhgm-Csf Versus Ifn-Alpha 2b In Cutaneous Melanoma Patients Stages Iib, Iic And Iii

Adjuvant treatment of high-risk cutaneous melanoma (CM) patients (pts) is still an unsolved issue, since the cost-benefit ratio of high-dose IFN-α2b is under discussion. The CSF-470 therapeutic vaccine, a mini-allograft of four lethally-irradiated allogeneic CM cell lines, with BCG and rhGM-CSF as adjuvants, is currently being tested in post-surgical adjuvancy vs medium-dose IFN-2b in stage IIB-III CM pts (phase II/III trial CASVAC-0401, NCT01729663).We present here the results of the phase II part of the study. A total of 31 pts (stage IIC = 2; stage III: 29) were enrolled: 20 pts were randomized to receive CSF-470 vaccine and 11 pts to IFN-α2b. Pts assigned to the vaccine arm received i.d. 1.6×10 7 CSF-470 irradiated cells plus 10 6 cfu BCG and 100μg rhGM-CSF (first day); 100 μg rhGM-CSF/day/3days were injected consecutively i.d. at the vaccination site. During the two-year treatment, pts in the vaccine arm received a total of 13 vaccinations. Pts assigned to the IFN-α2b arm received 10 MU/day/5 days a week for 4 weeks; then 5 MU 3/week for 23 months. Imaging studies were performed to follow the clinical evolution of the disease. Analysis of blood chemistry and differential white blood cell counts were performed to monitor systemic toxicity. Immune monitoring was performed at baseline and at 6, 12 and 24 months from protocol start. Also, pts were evaluated by Quality of Life Questionnaires (QOL) along the study. After including 20 pts who received a total of 176 vaccinations, we conclude that: CSF-470 vaccine was well tolerated; the main toxicity was a grade 2 reaction at the injection site; 3/20 pts presented grade 3 allergic reactions that were easily handled with anti-histamines and corticosteroids. Pts in the IFN-α2b arm presented grade 2-3 hematologic toxicity; 9 pts developed adverse events that forced treatment discontinuation provisionally or permanently. With a mean follow-up of 28 months and a maximum follow-up of 67 months, a significant benefit in the distant metastasis-free survival (DMFS) for CSF-470 was observed: 14/20 pts (70%) immunized with CSF-470 vaccine and only 4/11 pts (36.4%) in the IFN-α2b arm remain without distant metastases (p = 0.032). No significant differences in OS were yet observed. QOL was significantly superior for CSF-470 vaccine as compared to IFN-α2b treatment (p th and 12 th vaccine as compared to progressing pts. These results demonstrate a clear superiority of CSF-470 vaccine plus BCG plus GM-CSF vs IFN-α2b in the adjuvant setting in pts with high-risk CM. Citation Format: Jose Mordoh, Maria Betina Pampena, Mariana Aris, Paula Blanco, Alicia I. Bravo, Juan Manuel O9Connor, Julio Kaplan, Franco Ramello, Estrella M. Levy, Maria M. Barrio. A randomized phase II study of the CSF-470 therapeutic vaccine plus BCG plus rhGM-CSF versus IFN-α2b in cutaneous melanoma patients stages IIB, IIC and III. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT118. doi:10.1158/1538-7445.AM2015-CT118