A phase I study of intratumoral ipilimumab and interleukin-2 in patients with advanced melanoma

Abhijit Ray, Matthew A. Williams, Stephanie M. Meek, Randy C. Bowen, Kenneth F. Grossmann, Robert H.I. Andtbacka, Tawnya L. Bowles, John R. Hyngstrom, Sancy A. Leachman, Douglas Grossman, Glen M. Bowen, Sheri L. Holmen, Matthew W. VanBrocklin, Gita Suneja, Hung T. Khong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Purpose: Intratumoral interleukin-2 (IL-2) is effective but does not generate systemic immunity. Intravenous ipilimumab produces durable clinical response in a minority of patients, with potentially severe toxicities. Circulating anti-tumor T cells activated by ipilimumab may differ greatly from tumor-infiltrating lymphocytes activated by intratumoral ipilimumab in phenotypes and functionality. The objective of this study was to primarily assess the safety of intratumoral ipilimumab/IL-2 combination and to obtain data on clinical efficacy. Results: There was no dose limiting toxicity. While local response of injected lesions was observed in 67% patients (95% CI, 40%-93%), an abscopal response was seen in 89% (95% CI, 68%-100%). The overall response rate and clinical benefit rate by immune-related response criteria (irRC) was 40% (95% CI, 10%-70%) and 50% (95% CI, 19%-81%), respectively. Enhanced systemic immune response was observed in most patients and correlated with clinical responses. Experimental Design: Twelve patients with unresectable stages III/IV melanoma were enrolled. A standard 3+3 design was employed to assess highest tolerable intratumoral dose of ipilimumab and IL-2 based on toxicity during the first three weeks. Escalated doses of ipilimumab was injected into only one lesion weekly for eight weeks in cohorts of three patients. A fixed dose of IL-2 was injected three times a week into the same lesion for two weeks, followed by two times a week for six weeks. Conclusions: Intratumoral injection with the combination of ipilimumab/IL-2 is well tolerated and generates responses in both injected and non-injected lesions in the majority of patients.

Original languageEnglish (US)
Pages (from-to)64390-64399
Number of pages10
Issue number39
StatePublished - 2016


  • Abscopal effect
  • Immunotherapy
  • Interleukin-2
  • Intratumoral
  • Ipilimumab

ASJC Scopus subject areas

  • Oncology


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