In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 2507-2507
Kurzfassung:
2507 Background: Autologous monocyte-derived DC electroporated with synthetic mRNA encoding CD40 ligand, a constitutively active TLR4, and CD70 (TriMix-DC) have superior T-cell stimulatory capacity. In a pilot clinical trial, ID administration of TriMixDC-MEL (a mixture of TriMix-DC co-electroporated with mRNA encoding a fusion of DC.LAMP and 1 of 4 melanoma associated antigens) was immunogenic but resulted in limited anti-tumor activity in patients (pts) with advanced melanoma. Ipilimumab (IPI) is a CTLA-4 blocking mAb with established activity in pts with advanced melanoma. Methods: TriMixDC-MEL by the IV and ID-route was investigated as a single-agent or in combination with IPI (10 mg/kg q3wks x4, allowing for maintenance with IPI-alone q12wks in pts PFS at 〉 24 wks). Ratio of ID/IV administered DC: Cohort-1: 20.10 6 /4.10 6 DC [2pts], -2: 12.10 6 /12.10 6 DC [3pts], -3: 4.10 6 /20.10 6 [6pts], and -4: 0/24.10 6 DC [4pts]; DC were administered 4x q2w, and a 5 th administration on w16. in cohort-5, DC (4.10 6 -ID/20.10 6 -IV) were first administered alone and 2w thereafter in combination with IPI for a total of 4 administrations [6pts]. Results: Local skin reactions (gr1-2) were observed in all pts receiving DC ID, flu-like symptoms ( 〈 gr2) were observed in 12/21 pts, post IV-infusion chills (gr2) in 7/21 pts. Cytokines release (including a 〉 2-fold rise in the serum levels of IL-1RA, IL-6, IL-8, IL-17, G-CSF, IFN-g, MIP-1a, MIP-1b, TNF-a) was documented during chills. Best objective tumor response: 2x PR + 2x CR (by RECIST) out of 15 pts (27%) treated with DC-only (ongoing after 10+, 14+, 19+, and 20+ mths) and 3 PR out of 6 pts (all stage IV-M1c) treated with DC+IPI (ongoing after 5+, 5+, 6+ mths). Conclusions: ID/IV-administration of TriMixDC-MEL as a single-agent cellular immunotherapy or combined with IPI is associated with distinct but manageable side-effects and has clinical activity against pretreated advanced melanoma. Activity compares favorably with TriMixDC-MEL by ID-administration-only. Combined ID/IV administration of TriMixDC-MEL with IPI is currently under further evaluation in a phase II trial.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.2507
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2012
ZDB Id:
2005181-5
