30P - Safety, pharmacokinetics and pharmacodynamics from a clinical trial with healthy volunteers using the immunotherapeutic TLR-9 agonist MGN1703

Date 20 November 2015
Event ESMO Symposium on Immuno-Oncology 2015
Session Welcome reception and general Poster viewing
Topics Cancer Immunology and Immunotherapy
Presenter Alfredo Zurlo
Citation Annals of Oncology (2015) 26 (suppl_8): 5-14. 10.1093/annonc/mdv514
Authors A. Zurlo1, M. Schmidt2, A. Dax2, K. Kapp2, D. Oswald2, M. Schroff2, B. Wittig3
  • 1., Mologen AG, 14195 - Berlin/DE
  • 2., Mologen AG, Berlin/DE
  • 3Foundation Institute Molecular Biology And Bioinformatics, Freie Universitaet Berlin, 14195 - Berlin/DE

Abstract

Aim

The synthetic DNA-based immunomodulator MGN1703 is a potent TLR-9 agonist, activating the innate and adaptive immune system. MGN1703 has already shown a good safety profile and efficacy compared to placebo in patients receiving maintenance therapy for metastatic colorectal carcinoma (mCRC) in a randomised trial (MGN1703-C02, IMPACT).

Methods

A single dose crossover, placebo-controlled phase 1 trial (MGN1703-C04) to assess cardiac and general safety, pharmacokinetics (PK) and pharmacodynamics (PD) was conducted in healthy volunteers (HV). Fourteen HV were randomized to 2 groups and 13 subjects completed the study receiving a single subcutaneous (sc) dose of 60 mg MGN1703 during one treatment period and a single sc dose of placebo during the other.

Results

Seven of 13 HV experienced 21 adverse events (AE) after receiving MGN1703 (6 with 16 AE possibly or probably related); 6 of 14 HV experienced 11 AE after receiving placebo (3 with 5 AE possibly or probably related). All AE were mild or moderate in severity. No SAE was reported and no subject discontinued the study due to an AE. Changes in ECG numerical data were small and similar in both MGN1703 and placebo groups. The changes observed were not clinically significant and consistent with spontaneous variability and circadian change. Coagulation test results were within normal levels from screening throughout the study. There were no laboratory abnormalities reported as AE. The PK analysis of MGN1703 determined a mean Cmax of 189 ng/mL, a mean AUC0-t of 5001 ng•hr/mL, a median Tmax of 14 hours and a median t1/2 of 12.7 hours, confirming single dose data from cancer patients. All healthy volunteers had an increase in IP-10 concentration in serum app. 24 hours after injection of MGN1703. This is in line with expected time frame of immune activation subsequent to MGN1703 administration and with data from cancer patients.

Conclusions

The data confirm the good safety profile of MGN1703 and the PK/PD data from cancer patients. This supports the twice weekly application scheme of immunotherapy studies with MGN1703, e.g. the ongoing phase 3 IMPALA trial in mCRC patients.

Clinical trial identification

NCT01982747

Disclosure

A. Zurlo and M. Schroff: Are board members of Mologen AG. M. Schmidt, A. Dax and K. Kapp: Are employees of Mologen AG. B. Wittig: Is an advisor and shareholder of Mologen AG.