Poster Presentation Joint 2016 COSA and ANZBCTG Annual Scientific Meeting

Phase I trial of a nanocell packaged microRNA  therapy in malignant pleural mesothelioma (MPM) (#252)

Nick Pavlakis 1 , Steven Kao 2 , Michael Boyer 2 , Stephen Clarke 1 , Anthony Linton 3 , Himanshu Brahmbhatt 4 , Jennifer Mcdiarmid 4 , Yennie Huynh 5 , Felicity Leslie 5 , Helen Foster 4 , Scott Pattison 4 , Glen Reid 5 , Nico van Zanwijk 5
  1. Royal North Shore Hospital, St Leonards, NSW, Australia
  2. Chris O'Brien LIfehouse, Sydney, NSW, Australia
  3. Concord Repatriation General Hospital, Sydney, NSW, Australia
  4. EnGeneIC, Sydney, NSW, Australia
  5. Asbestos Disease Research Institute (ADRI), Sydney, NSW

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).