In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e19008-e19008
Kurzfassung:
e19008 Background: Patients with metastatic melanoma have a poor outcome. We hypothesize that combination immunotherapy can synergistically activate host immunity to generate an effective treatment option for high risk, resected stage III, recurrent, refractory or stage IV melanoma patients. Methods: We completed a phase II clinical trial of HyperAcute-Melanoma vaccine (HAM, NLG12036, NewLink Genetics) combined with pegylated interferon (Sylatron, Merck). Trial design was a 12-week regimen with the initial 4 weekly treatments consisting of HAM alone (intradermally) followed by 8 additional treatments of HAM + Sylatron (subcutaneously, 6 µg/kg). Trial endpoints include clinical response, overall safety and correlative findings for observed anti-tumor effect. Results: N=25, median age 60, 68% male with 21 patients completing the trial, 4 stopped due to progressive disease (PD). HAM-related common side effects include erythema and induration at the injection site, without significant grade 3 or 4 toxicities associated with the vaccine. By RECIST criteria, of 16 stage IV patients, there were 2 complete responders (CR), 2 with stable disease (SD) and 3 with no evidence of disease (NED) after resection. For stage III patients, 3/9 remain NED, 1 patient with slowly progressive disease remaining alive for over 30 months. The median overall survival is 29 months, with 50% of the patients surviving for 2 years and 12/25 (48%) still alive. The anti-αGal Ab values increased after vaccination in 24/25 patients by up to 100-fold (median 15, range 3-127). All evaluable patients (21/21) seroconverted, developing autoimmune antibodies. Anti-tyrosinase Ab’s developed in 7/23 correlating with 1 CR and 1 patient NED. Vitiligo developed in 4/25 patients, correlating with 2 CR and 2 NED. Conclusions: Combinatorial immunotherapy with HAM plus Sylatron shows clinical efficacy with tumor regression and concomitant immune activation. Optimization of dosing schedules and addition of other potentially synergistic agents should be explored to further enhance the benefit of this immunotherapeutic approach.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.e19008
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2012
ZDB Id:
2005181-5
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