MesomiR 1: A Phase I study of TargomiRs in patients with refractory malignant pleural mesothelioma (MPM) and lung cancer (NSCLC)

Abstract

Background: Recently we demonstrated that members of the miR-15/16 family of microRNAs are implicated as tumor suppressors in MPM. The MesomiR 1 study is a first in man ongoing phase I study testing treatment with miR-15 /16 mimics packaged in EDV TM nanocells targeted with EGFR antibodies (TargomiRs). Methods: Dose escalation phase I study where patients are allowed to continue experimental therapy beyond the phase I period, if TargomiRs are well tolerated. Fifty per cent of the MTD established for EDV TM nanocells = 5 billion nanocells loaded with 1.5 µg miR 15/16 mimics (TargomiRs), was chosen as the first dose level. The study uses a standard 3-6 patient dose escalation cohort design examining weekly/twice weekly schedules with 3 planned dose levels in 6 cohorts. Based on prior experience with EDV TM nanocells, starting dose is modified for individual patients with elevated (> 5pg/mL) baseline IL-6 levels. All patients receive premedication with dexamethasone, promethazine and paracetamol and are monitored for a minimum period 3 hours after the TargomiR infusion. If treatment is well tolerated it can be repeated on 8 weeks cycles followed by repeat imaging. Quality of Life questionnaires are completed on a weekly basis. Results: The study commenced in Sep 2014 and is open in 3 centres. Five MPM patients enrolled to date received 5 billion TargomiRs and experienced a short (<20 minutes) period of shivering/rigor 80-90 minutes after the start of the infusion with 2 describing a burning/painful sensation in the diseased chest area. 4/5 patients have completed the initial period of 8 weekly infusions. Blood examination shortly after infusion revealed a steep but transitory rise in inflammatory cytokines, neutrophilia and lymphopenia, accompanied by (temporary) elevation of liver enzymes. 3/5 patients demonstrated improvement of quality of life parameters during the therapy period. Tumour imaging is pending and 1 patient is scheduled to continue therapy beyond 8 weeks. Conclusions: The MesomiR 1 study is ongoing. TargomiR infusions in the first 5 patients were well tolerated and associated with transient cytokine-mediated reactions. reference Reid G et al., Annals of Oncology 24: 3128-3135, 2013.