A Phase II Randomized Study of CDX-1401, a Dendritic Cell Targeting NY-ESO-1 Vaccine, in Patients with Malignant Melanoma Pre-Treated with Recombinant CDX-301, a Recombinant Human Flt3 Ligand.

9589 Background: Patients (pts) with high-risk melanoma have a 20-60% recurrence rate with 5-year OS between 45% and 70%. The adjuvant setting is an opportunity to test prevention vaccines that may have efficacy against disease recurrence. We evaluated CDX301, a recombinant human Flt3 ligand (Flt3L), plus vaccination with CDX1401, a fusion protein consisting of human monoclonal IgG1 antibody targeting the dendritic cell (DC) receptor DEC-205 linked to the NY-ESO-1 tumor antigen, in a phase II, open-label, multicenter, randomized study of subjects with resected melanoma, to determine whether immune responses to NY-ESO-1 elicited by vaccination with CDX1401 + poly-ICLC are substantially increased by prior expansion of circulating DC with Flt3L therapy. Methods: 60 pts with resected melanoma were randomized to two cohorts: Cohort 1 received CDX301 pretreatment (25 ug/kg SC x 10 days) in 2 of 4 monthly cycles of vaccination with CDX1401 (1mg IC) + poly-ICLC (2mg SC, days 1 and 2). Cohort 2 received 4 monthly cycles of vaccine with CDX1401 and poly-ICLC without prior CDX301. We also assessed immunogenicity to other melanoma-associated antigens and memory viral responses, character of PBMC subsets, and safety, tolerability and clinical efficacy of the regimens. Results: Both treatments were well tolerated with grade 1-2 AEs of chills, injection site erythema and pain, fever and myalgias most common. Disease recurred in 8 of 60 pts. Two of the 8 pts progressed prior to completing 4 cycles of treatment. Preliminary analyses show substantial (between ~15- to ~200-fold) increases of PBMC innate immune cells (DC, monocytes and NK cells) in subjects from cohort 1 vs cohort 2. Further, there was development of higher anti-NY-ESO-1 antibody titers in cohort 1 vs cohort 2. Comparative immune cell gene expression profiling of PBMC are consistent with these differences. Finally, significant NY-ESO-1 specific immune T cell responses were observed and differences between cohorts are being analyzed. Data from all 60 patients will be presented. Conclusions: DC mobilization with Flt3L is safe and may enhance responses to DC targeted vaccines. Clinical trial information: NCT02129075.