A phase I/IIa clinical trial in stage IV melanoma of an autologous tumor-dendritic cell fusion (dendritoma) vaccine with low dose interleukin-2

Stage IV melanoma has high mortality, largely unaffected by traditional therapies. Immunotherapy including cytokine therapies and checkpoint inhibitors improves outcomes, but has significant toxicities. In this phase I/IIa trial, we investigated safety and efficacy of a dendritoma vaccine, an active, specific immunotherapy, in stage IV melanoma patients. Autologous tumor lysate and dendritic cells were fused creating dendritoma vaccines for each patient. Phase I patients were vaccinated every 3 months with IL-2 given for 5 days after initial inoculation. Phase IIa patients were vaccinated every 6 weeks with IL-2 given on days 1, 3 and 5 after initial inoculation. Toxicity and clinical outcomes were assessed. Twenty-five patients were enrolled and inoculated. All dendritoma and IL-2 toxicities were < grade 3. Median overall survival (OS) was 16.1 months with projected 5-year survival = 29 %. Significant OS improvement for patients receiving a parts per thousand yen3 versus < 3 inoculations (43.1 vs. 16.7 %, p = 0.02) was observed. Patients with no evidence of disease (NED) showed improved OS (80 vs. 14 %, p = 0.005). No clinicopathologic differences were present between phase I (n = 10) and IIa (n = 15) patients; phase IIa patients received more frequent dosing and higher mean number of inoculations. Phase IIa median OS was significantly higher (23.8 vs. 8.7 months, p = 0.004). The dendritoma vaccine has minimal toxicity profile with potential clinical benefit. There was OS advantage for NED stage IV patients, those receiving higher number of doses and increased frequency. Based on these results, we initiated a phase IIb trial utilizing improved dendritoma technology in the adjuvant setting for NED stage III/IV melanoma patients.