An Open-Label, Randomized, Multi-Center Study Comparing the Sequence of High Dose Aldesleukin (Interleukin-2) and Ipilimumab (Yervoy) in Patients with Metastatic Melanoma.

Combination immunotherapy with sequential administration may enhance metastatic melanoma (MM) patients with long-term disease control. High Dose Aldesleukin/Recombinant Interleukin-2 (HD rIL-2) and ipilimumab (IPI) offer complementary mechanisms against MM. This phase IV study assessed the sequenced use of HD rIL-2 and IPI in MM patients. Eligible Stage IV MM patients were randomized to treatment with either two courses of HD rIL-2(600,000 IU/kg) followed by four doses of IPI 3 mg/kg or vice-versa. The primary objective was to compare one-year overall survival (OS) with historical control (46%, Hodi et al., NEJM 2010). Secondary objectives were 1-year progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) profile. Evaluable Population (EP) included patients who received at least 50% of planned treatment with each drug. Thirteen and 16 patients were randomized to receive HD rIL-2 first, and IPI first, respectively. One-year OS rate was 75% for intention to treat population. Eighteen patients were included in EP, 8 in HD rIL-2, 10 in IPI first arm. In EP, 1-year OS, PFS and ORR rates were 87%, 68%, and 50%, respectively. The frequency of AEs was similar in both arms with 13 patients experiencing Grade 3 or higher AEs, 3 resulting in the end of study participation. There was one HD rIL-2-related death, from cerebral hemorrhage due to thrombocytopenia. In this study with small sample size, HD rIL-2 and IPI were safe to administer sequentially in MM patients and showed more than additive effects. 1-year OS was superior to that of IPI alone from historical studies.

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© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

Déclaration de conflit d'intérêts

MH, DRM, RH, BT, LFl, LFe have no conflicts of interest to disclose. WHS reports grants and personal fees from Bristol-Myers Squibb, during the conduct of the study; grants and personal fees from Merck, grants and personal fees from Novartis, personal fees from Regeneron, grants from Genentech, outside the submitted work. LDC’s institution (University of Arizona) received payments from Prometheus Laboratories to support the conduct of this study. LDC receives research funding, paid to the institution (University of Washington), from Eli Lilly, AADi, BluePrint Medicine, Iterion, Gradalis, Philogen, Advenchen Laboratories, and CBA Pharma. LDC has received honoraria or has served on advisory boards for Daaichi Sankyo, BluePrint Medicines, and Regeneron. GAD reports position at the advisory board for Clinigen and institutional research support from Bristol-Myers Squibb and Clinigen. SH reports position at advisory board for Cardinal Health, Bristol-Myers Squibb, Immunomedics, Pfizer, and Speakers bureau at Bristol-Myers Squibb. MM reports other interests from Exicure, Blueprints Medicine, Immunocore, Amgen, Trieza, Array Biopharma, Biontech, and Novartis, outside the submitted work. GD reports fees from Novartis, Merck & Co, and Bristol-Myers Squibb. NG is employed by study sponsor Prometheus Labs, Clinigen, Inc. SPP reports institutional clinical trial support from Bristol Myers Squibb, InxMed, Novartis, Provectus, and Reata; advisory board participation for Cardinal Health and Castle Biosciences; data safety monitoring board activities for Immunocore, and personal fees from Merck outside the submitted work.