A Phase I/IIa Clinical Trial of an Autologous Tumor/Dendritic Cell Fusion (Dendritoma) Vaccine with Low Dose Interleukin-2 in Stage IV Melanoma

Julia M Greene MD, BSc1, Erika J Schneble Md1, Xianzhong Yu2, Thomas E Wagner PhD2, George E Peoples3. 1San Antonio Military Medical Center, 2Perseus PCI, 3Cancer Insight

BACKGROUND: Stage IV melanoma has a high mortality rate. Traditional systemic therapies have shown limited benefit; however, several immunotherapies including cytokine therapies and checkpoint inhibitors have shown promise. Unfortunately, these immunotherapies are effective in only a small number of patients (pts), are non-specific and often toxic. We investigated a non-toxic and active specific form of immunotherapy, our dendritoma vaccine (DV), in late stage melanoma pts in a phase I/IIa trial.

METHODS: Autologous tumor and dendritic cells are fused, and sorted to create a DV for each stage IV melanoma pt. In the phase I, 10 pts were vaccinated every 3mos with doses of 0.5-1.0×106 DV. IL-2 was initiated on day 1 after vaccination, and increased from 3-9MIU/m2/day as tolerated for 5 days. In the phase IIa, 15 pts were vaccinated with doses from 0.25-1.0×106 DV every 6 wks up to 6 inoculations. IL-2 (3MIU/m2/day) was given on days 1, 3, and 5 after vaccination.

RESULTS: In the combined phase I/IIa trials (n=25), there were no grade 3-5 toxicities. There was a 24% pCR, and a 32% overall survival (OS) rate at 5 yrs. The median OS was 16.1mos compared to a historical 8.5mos. An increase in OS (75% vs 23.8%, p=0.065) was seen in pts with stage IV resected disease (n=4) versus all others and in pts receiving >3 vs <3 inoculations (45.5% vs 21.4%, p=0.07). Comparing phase I and IIa, there were no differences in pt characteristics (all p>0.1) yet median OS of phase I pts was 8.7mos vs 21.5mos for phase II pts. There was a higher dose of IL-2 and higher DV dose (710,983 vs 402,540 dendritomas (p=0.0006)) in the phase I but more frequent dosing and higher mean number of inoculations (3 vs 2.3 p=0.27) in the phase IIa.

CONCLUSIONS: The dendritoma vaccine potentially provides a clinical benefit without toxicity. There was an apparent dose response for inoculation number but not dose of the DV. Patients with resected stage IV disease benefited most. We have initiated a phase IIb trial in stage III/IV (resected) melanoma pts in the adjuvant setting to prevent recurrence.

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