Pilot Trial of the hu14.18-IL2 Immunocytokine in Patients with Completely Resectable Recurrent Stage III or Stage IV Melanoma
Phase I testing of the hu14.18-IL2 immunocytokine (IC) in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m(2)/day. Preclinical data in IC-treated tumor-bearing mice with low tumor burden documented striking antitumor effects. Patients with completely resectable recurrent stage III or stage IV melanoma were scheduled to receive 3 courses of IC at 6 mg/m(2)/day i.v. on days 1, 2 and 3 of each 28-day course. Patients were randomized to complete surgical resection either following neoadjuvant (Group A) or prior to adjuvant (Group B) IC course 1. Primary objectives were to: (1) evaluate histological evidence of anti-tumor activity and (2) evaluate recurrence-free survival (RFS) and OS. Twenty melanoma patients were randomized to Group A (11 patients) or B (9 patients). Two Group B patients did not receive IC due to persistent disease following surgery. Six of 18 IC-treated patients remained free of recurrence, with a median RFS of 5.7 months (95% confidence interval (CI) 1.8-not reached). The 24-month RFS rate was 38.9% (95% CI 17.5-60.0%). The median follow-up of surviving patients was 50.0 months (range: 31.8-70.4). The 24-month OS rate was 65.0% (95% CI 40.3-81.5%). Toxicities were similar to those previously reported. Exploratory tumor-infiltrating lymphocyte (TIL) analyses suggest prognostic value of TILs from Group A patients. Prolonged tumor-free survival was seen in some melanoma patients at high risk for recurrence who were treated with IC.
Albertini, M., Yang, R., Ranheim, E., Hank, J., Zuleger, C., Weber, S., Neuman, H., Hartig, G., Weigel, T., Mahvi, D., Henry, M., Quale, R., McFarland, T., Gan, J., Carmichael, L., Kim, K., Loibner, H., Gillies, S., & Sondel, P. (2018). Pilot Trial of the hu14.18-IL2 Immunocytokine in Patients with Completely Resectable Recurrent Stage III or Stage IV Melanoma. Cancer Immunology, Immunotherapy, 67 (10), 1647-1658. https://doi.org/10.1007/s00262-018-2223-z