MPM is in desperate need of new therapies.
MesomiR 1 is the first-in-man phase I study
testing the intravenous administration of TargomiRs. TargomiRs
are nanocells (EDVTM) targeted with EGFR antibodies and
packaged with miR-15/16- derived
microRNA mimics.
We report findings in patients with refractory MPM.
Methods: 3-6 patient dose escalation cohort design
with weekly/twice weekly TargomiR infusions for 8 weeks.
The 1st dose level was set at 50% of the previous maximal tolerated dose
for EDVs (= 5 billion TargomiRs packaged with 1.5 ug
miR-15/16 mimics). CT (for modified RECIST), FDG-PET and pulmonary function
assessments were scheduled 8 weekly.
Results: 22 patients are enrolled: 17 male, 5 female
receiving different doses and schedules
from 1 billion (once a week) to 5 billion
(twice a week). Currently more than 240 weeks of TargomiR
treatment is being analysed.
Immediate toxicity includes transient inflammatory symptoms such as shivering/
rigor, temperature elevation and pain at tumour noted 60-90 min after TargomiR infusion.
These are accompanied by neutrophilia, lymphopenia, hypophosphatemia,
and sometimes elevation of liver enzymes. Transient
(asymptomatic) ECG (ST-T) changes were noted in 4 patients,
thought to be associated with the inflammatory syndrome.
Response: One near-complete response, 11 patients with stable disease at 8 weeks,
with 2 patients on treatment > 40 weeks.
Conclusion: Weekly infusions of 5 billion TargomiRs are
well tolerated. Transient inflammatory symptoms
after infusion in the clinic are the main toxicities accompanied by
a dynamic pattern of changes in haematologic
and non-haematologic blood parameters after TargomiR infusion.
Documentation of objective response and
stable disease after 8 weeks of TargomiR treatment
point to single agent activity of TargomiRs.
The study is ongoing aiming to accrue 7 more patients.
(NCT02369198/ ANZCTR-ACTRN12614001248651).