Phase II trial of hu14.18-IL2 (EMD 273063) for patients with metastatic melanoma

Abstract

9039 Background: The hu14.18-IL2 immunocytokine consists of a humanized anti-GD2 monoclonal antibody linked to IL2. It has potent preclinical activity against melanoma (MEL) and neuroblastoma (NBL), particularly in the setting of minimal residual disease (MRD). Recent Phase I trials of hu14.18-IL2 in patients (pts) with MEL or NBL showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m2/d for MEL. Five MEL pts with non-evaluable disease showed long disease free survival (range: 6- > 106 months). A recently completed phase II study (separate ASCO abstract) for NBL showed antitumor activity in pts with MRD. Methods: All pts had measurable metastatic MEL. Hu14.18-IL2 was given at 6 mg/m2/d as a 4h i.v. infusion on d 1, 2, and 3 of each 28d treatment cycle. Pts with stable disease (SD) or regression following cycle 2 were eligible to receive 2 additional cycles of therapy. The primary study objective was to evaluate clinical anti-tumor activity and duration of response, and secondary objectives included evaluating adverse events and immunologic activation of this treatment. Fourteen pts were planned for the 1st stage of this 30-pt 2-stage study. Results: 14 pts received 2 cycles of treatment, and 5 of them received cycles 3 & 4. One pt had a confirmed partial response (PR), 4 pts had stable disease (SD), and 9 pts had progressive disease [1 PR of 14 pts = response rate (RR) of 7.1%; confidence interval 0.2%-33.9%]. The PR and SD responses lasted 1–4 months. Toxicities resulting in dose reduction included grade 3 hypotension (2 pts) and grade 2 renal with oliguria (1 pt); all toxicities were reversible. Pts had a peripheral blood lymphocytosis on d 8 and increased C-reactive protein. Conclusions: Hu14.18-IL2 at 6 mg/m2/d met protocol criteria to initiate stage 2 of pt accrual (ie: treat 16 additional pts). Due to limited availability of hu14.18-IL2, we suspended stage 2. Instead our ongoing testing of hu14.18-IL2 is focused on (a) testing in pts with MRD setting (recurrent stage III or stage IV MEL with CR after surgical resection) and (b) combining hu14.18-IL2 in with anti-integrin therapy based on striking preclinical anti-tumor effects. The goal is to see if efficacy is greater in the MRD setting, as seen in mice and in pts with NBL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration EMD Pharmaceuticals, Inc., Lexigen-EMD EMD Pharmaceuticals, Lexigen-EMD, Merck KGaA EMD Pharmaceuticals