Original Articles: Clinical researchPhase Ib/II trial testing combined radiofrequency ablation and ipilimumab in uveal melanoma (SECIRA-UM)Rozeman, Elisa A.a; Prevoo, Warnerb; Meier, Mark A.J.b; Sikorska, Karolinac; Van, Trieu M.d; van de Wiel, Bart A.e; van der Wal, Jacqueline E.e; Mallo, Henk A.a; Grijpink-Ongering, Lindsay G.c; Broeks, Annegienf; Lalezari, Ferryb; Reeves, Jasong; Warren, Sarahg; van Thienen, Johannes V.a; van Tinteren, Harmc; Haanen, John B.A.G.a; Kapiteijn, Ellenh; Blank, Christian U.aAuthor Information Departments of aMedical Oncology bRadiology, The Netherlands Cancer Institute (NKI), Amsterdam cDepartment of Biometrics dDivision of Molecular Oncology and Immunology eDepartment of Pathology fCore Facility Molecular Pathology and Biobanking, NKI, Amsterdam, The Netherlands gNanoString Technologies, Seattle, Washington, USA hDepartment of Medical Oncology, LUMC, Leiden, The Netherlands Received 3 October 2019 Accepted 7 November 2019 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Present affiliation: Warner Prevoo, Department of Radiology, OLVG, Amsterdam, the Netherlands Present affiliation: Mark A.J. Meier, Department of Radiology, ISALA, Zwolle, the Netherlands Correspondence to Christian U. Blank, Division of Molecular Oncology and Immunology, Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands, Tel: +31 20 5129111; fax: +31 20 5122572; e-mail: firstname.lastname@example.org Melanoma Research: June 2020 - Volume 30 - Issue 3 - p 252-260 doi: 10.1097/CMR.0000000000000653 Buy SDC Metrics Abstract Approximately, 50% of patients with uveal melanoma develop distant metastasis for which no standard therapy is established. In contrast to cutaneous melanoma, the anti-CTLA-4 antibody ipilimumab showed no clinical activity in uveal melanoma. Liver directed therapies improve local control, but fail to show overall survival (OS) benefit. Preclinical experiments demonstrated that radiofrequency ablation (RFA) induced durable responses in combination with anti-CTLA-4. The aim of this phase Ib/II study was to assess safety and efficacy of RFA plus ipilimumab in uveal melanoma. Patients underwent RFA of one liver lesion and subsequently received four courses ipilimumab 0.3, 3 or 10 mg/kg every 3 weeks in a 3 + 3 design. Primary endpoints were safety in terms of dose limiting toxicities per cohort to define the recommended phase II dose (RP2D) in the phase Ib part and confirmed the objective response rate and disease control rate (DCR) of non-RFA lesions in the phase II part. Secondary endpoints were progression-free survival (PFS) and OS. Ipilimumab 10 mg/kg + RFA was initially defined as the RP2D. However, after 19 patients, the study was amended to adjust the RP2D to ipilimumab 3 mg/kg + RFA, because 47% of patients treated with 10 mg/kg had developed grade 3 colitis. In the 3 mg/kg cohort, also 19 patients have been treated. Immunotherapy-related grade ≥3 adverse events were observed in 53% of patients in the 10 mg/kg cohort versus 32% in the 3 mg/kg cohort. No confirmed objective responses were observed; the confirmed DCR was 5% in the 10 mg/kg cohort and 11% in the 3 mg/kg cohort. Median PFS was 3 months and comparable for both cohorts, median OS was 14.2 months for the 10 mg/kg cohort versus 9.7 months for the 3 mg/kg cohort. Combining RFA with ipilimumab 3 mg/kg was well tolerated, but showed very limited clinical activity in uveal melanoma. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.