AUTHOR=Mordoh José , Pampena María Betina , Aris Mariana , Blanco Paula Alejandra , Lombardo Mónica , von Euw Erika María , Mac Keon Soledad , Yépez Crow Michelle , Bravo Alicia Inés , O’Connor Juan Manuel , Orlando Ana Gabriela , Ramello Franco , Levy Estrella Mariel , Barrio María Marcela 

TITLE=Phase II Study of Adjuvant Immunotherapy with the CSF-470 Vaccine Plus Bacillus Calmette–Guerin Plus Recombinant Human Granulocyte Macrophage-Colony Stimulating Factor vs Medium-Dose Interferon Alpha 2B in Stages IIB, IIC, and III Cutaneous Melanoma Patients: A Single Institution, Randomized Study

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00625

DOI=10.3389/fimmu.2017.00625

ISSN=1664-3224

ABSTRACT=<p>The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette–Guerin (BCG) and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) is being tested against medium-dose IFN-α2b in stages IIB–III cutaneous melanoma (CM) patients (pts) after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (<uri xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</uri>: NCT01729663). Thirty-one pts were randomized to the CSF-470 vaccine (<italic>n</italic> = 20) or to the IFN-α2b arm (<italic>n</italic> = 11). During the 2-year treatment, immunized pts should receive 13 vaccinations. On day 1 of each visit, 1.6 × 10<sup>7</sup> irradiated CSF-470 cells plus 10<sup>6</sup> colony-forming units BCG plus 100 µg rhGM-CSF were administered intradermally, followed on days 2–4 by 100 µg rhGM-CSF. IFN-α2b pts should receive 10 million units (MU)/day/5 days a week for 4 weeks; then 5 MU thrice weekly for 23 months. Toxicity and quality of life (QOL) were evaluated at each visit. With a mean and a maximum follow-up of 39.4 and 83 months, respectively, a significant benefit in the distant metastasis-free survival (DMFS) for CSF-470 was observed (<italic>p</italic> = 0.022). Immune monitoring showed an increase in antitumoral cellular and humoral response in vaccinated pts. CSF-470 was well tolerated; 20/20 pts presented grades 1–2 dermic reactions at the vaccination site; 3/20 pts presented grade 3 allergic reactions. Other adverse events (AEs) were grade 1. Pts in the IFN-α2b arm presented grades 2–3 hematological (7/11), hepatic (2/11), and cardiac (1/11) toxicity; AEs in 9/11 pts forced treatment interruptions. QOL was significantly superior in the vaccine arm (<italic>p</italic> &lt; 0.0001). Our results suggest that CSF-470 vaccine plus BCG plus GM-CSF can significantly prolong, with lower toxicity, the DMFS of high-risk CM pts with respect to medium-dose IFN-α2b. The continuation of a Phase III part of the CASVAC-0401 study is encouraged.</p>