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Background
MGN1703 is a synthetic DNA-based TLR-9 agonist which has shown a good safety profile
and a benefit compared to placebo in maintenance therapy of patients with metastatic
colorectal carcinoma.
Methods
In addition to the phase 1 and 2 trials with cancer patients a single dose crossover
placebo-controlled phase 1 trial, MGN1703-C04, was performed to assess safety, pharmacokinetics
(PK) and pharmacodynamics in healthy volunteers (HV).
Results
Standard PK parameters like mean Tmax (14 h), AUC0-t (5001 ng h/mL) and shape of the curve in the MGN1703-C04 trial were similar to single dose
data obtained from cancer patients, with mean Tmax of 10 h and AUC0-t of 5336 ng h/mL. Notably, multiple doses resulted in similar levels without accumulation of MGN1703.
In MGN1703-C04 elevated IP-10 levels were detected in the serum of HV peaking at 24–48 h after dosing with MGN1703. The elevation of IP-10 is in keeping with data from cancer
patients, which additionally showed activation of innate immune cells after dosing
with MGN1703, e.g. up-regulation of CD169 on blood monocytes.
Conclusions
The data show similarities between HV and cancer patients with respect to PK and –
following-up downstream – the immunomodulatory profile, supporting the twice weekly
application scheme of ongoing cancer studies. Further data will allow evaluation of
possible association with clinical parameters.
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