Treatment of metastatic uveal melanoma with adoptive transfer of tumor infiltrating lymphocytes: a single-center phase 2 study

Background—Uveal melanoma is a rare tumor with no established treatments once metastases develop. Although a variety of immune based therapies have demonstrated efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T cell therapy has shown salvage responses in multiple refractory solid tumors. Thus, we sought to determine if adoptive transfer of autologous tumor infiltrating lymphocytes (TIL) could mediate regression of metastatic uveal melanoma. Methods—In this ongoing single-center, two-stage phase 2, single-arm trial, patients with histologically confirmed metastatic ocular melanoma (aged ≥ 16 years) were enrolled. Key eligibility criteria were an ECOG performance status of 0 or 1, progressive metastatic disease, and adequate hematological, renal, and hepatic function. Metastasectomy operations were performed to procure tumor tissue to generate autologous TIL cultures, which then underwent large scale ex vivo expansion. Patients were treated with lymphodepleting conditioning chemotherapy followed by intravenous infusion of autologous TIL and high-dose interleukin-2. The primary end-point was objective tumor response in evaluable patients per protocol using Response to Evaluation Criteria Correspondence: Udai S. Kammula, M.D., Surgery Branch, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Building 10-Hatfield CRC, Rm 3-5930, Bethesda, MD, 20892-1201, Tel: 301-435-8606, Fax: 301-435-5167, udai_kammula@nih.gov. Conflicts of Interest: None AUTHOR CONTRIBUTIONS: USK conceived and designed the study. SSC, RPTS, JCY, RMS, CAK, SLG, JRW, DND, DZ, BCP, ACS, AKS, LX, THP, MR, DEW, MAT, SAR, and USK collected and assembled the data. All authors analyzed and interpreted the data, wrote the manuscript, and approved the final version of the manuscript. DECLARATION OF INTERESTS: CAK reports personal fees from Cell Design Labs and Obsidian Therapeutics unrelated to the submitted work. The other authors declared no conflicts of interest. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author manuscript Lancet Oncol. Author manuscript; available in PMC 2018 June 01. Published in final edited form as: Lancet Oncol. 2017 June ; 18(6): 792–802. doi:10.1016/S1470-2045(17)30251-6. A uhor M anscript