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Phase II trial of hu14.18-IL2 for patients with metastatic melanoma

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Abstract

Phase I testing of the hu14.18-IL2 immunocytokine in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m2/day. In this phase II study, 14 patients with measurable metastatic melanoma were scheduled to receive hu14.18-IL2 at 6 mg/m2/day as 4-h intravenous infusions on Days 1, 2, and 3 of each 28 day cycle. Patients with stable disease (SD) or regression following cycle 2 could receive two additional treatment cycles. The primary objective was to evaluate antitumor activity and response duration. Secondary objectives evaluated adverse events and immunologic activation. All patients received two cycles of treatment. One patient had a partial response (PR) [1 PR of 14 patients = response rate of 7.1 %; confidence interval, 0.2–33.9 %], and 4 patients had SD and received cycles 3 and 4. The PR and SD responses lasted 3–4 months. All toxicities were reversible and those resulting in dose reduction included grade 3 hypotension (2 patients) and grade 2 renal insufficiency with oliguria (1 patient). Patients had a peripheral blood lymphocytosis on Day 8 and increased C-reactive protein. While one PR in 14 patients met protocol criteria to proceed to stage 2 and enter 16 additional patients, we suspended stage 2 due to limited availability of hu14.18-IL2 at that time and the brief duration of PR and SD. We conclude that subsequent testing of hu14.18-IL2 should involve melanoma patients with minimal residual disease based on compelling preclinical data and the confirmed immune activation with some antitumor activity in this study.

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Acknowledgments

We thank Barrett P. Wagner for technical assistance and Laddie Johnson for assistance with manuscript preparation. We also thank the nurses on the UW CTRC for outstanding nursing care and for clinical trial support. This material was supported by National Institutes of Health Grants CA032685, CA87025, and grants from the Midwest Athletes for Childhood Cancer Fund, the Crawdaddy Foundation; CTRC grant (GM067386); grant P30 CA014520 from the National Cancer Institute; the Gretchen and Andrew Dawes Melanoma Research Fund; Ann’s Hope Foundation; the Jay Van Sloan Memorial from the Steve Leuthold Family; and the Tim Eagle Memorial.

Conflict of interest

The authors have the following financial or other conflicts of interests to disclose related to this publication: The commercial rights to hu14.18-IL2 IC are now held by Apeiron-Biologics AG of Vienna Austria. They were licensed from Merck Serono of Darmstadt Germany. A separate (subsequent and ongoing) trial of hu14.18-IL2 in patients with melanoma, chaired by Dr. Mark Albertini and involving this clinical team, received partial per patient research support for components of the clinical study from Merck Serono. No direct support from Merck Serono was received regarding the study reported on here. Dr. Gillies has a patent related to hu14.18-IL2 that he has licensed to Merck Serono.

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Authors and Affiliations

  1. University of Wisconsin Carbone Cancer Center, Madison, WI, USA

    Mark R. Albertini, Jacquelyn A. Hank, Jordan Kostlevy, Jennifer Haldeman, Heidi Schalch, Jacek Gan, KyungMann Kim, Jens Eickhoff & Paul M. Sondel

  2. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Mark R. Albertini

  3. Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Jacquelyn A. Hank, Jacek Gan & Paul M. Sondel

  4. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Brian Gadbaw & Paul M. Sondel

  5. Department of Biostatistics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    KyungMann Kim & Jens Eickhoff

  6. Provenance Biopharmaceuticals Inc., Waltham, MA, USA

    Stephen D. Gillies

  7. Medical Service, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA

    Mark R. Albertini

  8. K6-530 Clinical Science Center, 600 Highland Avenue, Madison, WI, 53792, USA

    Mark R. Albertini

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  1. Mark R. Albertini
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Correspondence to Mark R. Albertini.

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Albertini, M.R., Hank, J.A., Gadbaw, B. et al. Phase II trial of hu14.18-IL2 for patients with metastatic melanoma. Cancer Immunol Immunother 61, 2261–2271 (2012). https://doi.org/10.1007/s00262-012-1286-5

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  • DOI: https://doi.org/10.1007/s00262-012-1286-5

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