A phase I trial of intra-lymph-node administration of a novel immunotherapeutic regimen (MKC1106-MT) in patients with advanced melanoma.

8535 Background: MKC1106-MT is an immunotherapeutic consisting of recombinant plasmid pMEL-TYR containing Melan-A (MEL) and tyrosinase (TYR) antigen fragments and 2 peptide (E-MEL; E-TYR) analogs corresponding to an HLA-A*0201-restricted epitopes from each. Methods: Patients received a prime-boost with a fixed priming of the plasmid (2,400 μ g/dose) via ultrasound guided injections into inguinal or axillary nodes on days 1, 4, 15 and 18 followed by peptide on days 29 and 32; cycles were repeated every 43 days. Either 100 mg/dose or 300 mg/dose of each peptide were given. Patients were HLA*0201+, and had stage IIIB/C or IV melanoma positive for MEL and TYR. Clinical evaluations occurred at baseline and the end of each cycle. Patients without disease progression received up to 8 cycles of treatment. Immune responses using PBMCs were measured days 29 and 39 of each cycle by MHC tetramer and IFN gamma ELISPOT for MEL and TYR epitopes. Results: 18 pts were enrolled: 7 in the low dose and 11 in the high dose peptide cohort. Therapy was well tolerated, with no DLTs. No differences in safety or immune responses were seen between the 2 cohorts. The most frequent treatment-related AEs were: fatigue (grade 1-2), chills (grade 1-2) and brief pain at injected sites (grade 1-2). At 1 year, 4 pts, all with nodal metastases showed ORs (1 CR, 2 PRs and 1 SD by RECIST) and all exhibited high baseline levels of MEL T cells. Among two biopsies of regressing lesions one had a dense infiltration of CD8+ T cells with ∼1% TILs being specific for the MEL epitope targeted by MKC1106-MT. Conclusions: Repeated intra-lymph node administration of MKC1106-MT is feasible, safe, induces objective tumor regression and correlates with baseline immunity to MEL. % tetramer MEL+/total CD8+ at baseline (median; range) No OR OR Detectable 4/14 pts ( 0.25; 0.2-0.31) 4/4 pts (0.2; 0.11-0.23) Low/None detectable 10/14 pts (0.06; 0-0.08) 0/4 pts Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Mannkind Mannkind Mannkind