A phase I study of intratumoral injection of ipilimumab and interleukin-2 in patients with unresectable stage III-IV melanoma.

3018 Background: Intratumoral (IT) IL-2 is highly effective and well tolerated, but does not generate systemic immunity or response in untreated lesions. Intravenous (IV) ipilimumab (Ipi) lowers the threshold for T cell activation leading to a durable clinical response in a minority of melanoma patients, but is associated with potentially severe toxicities. Since IV Ipi doesn’t have tissue distribution, circulating anti-tumor T cells activated by this drug may differ greatly from tumor-infiltrating lymphocytes (TILs) activated by IT Ipi in terms of quantity and quality. Therefore, we hypothesized that a combination of IT IL-2 and IT Ipi would effectively hyperactivate and expand TILs to engender systemic immunity with minimal toxicity. Methods: This was a phase I dose escalation study for Ipi with fixed dose IL-2 in patients with unresectable stage III/IV melanoma and at least one injectable lesion. A single lesion (0.5-2.0 cm) in each patient was treated with IL-2 (3 mIU) IT TIW x 2 weeks, then BIW x 6 w...