In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 3643-3643
Abstract:
3643 Background: Standard induction chemotherapy for mCRC is often discontinued in patients responding to the treatment. MGN1703, a synthetic DNA-based immunomodulator, acts as TLR-9 agonist. This trial has been conducted to assess clinical efficacy, safety, and immunogenicity of MGN1703 as maintenance therapy vs placebo. Methods: The IMPACT trial is an international, multicenter, randomized (2:1) double-blind placebo-controlled phase 2 trial in mCRC patients with disease control (CR, PR, SD) after 4.5 to 6 months of 1st-line induction chemotherapy with FOLFOX/XELOX or FOLFIRI +/- bevacizumab. Results: 59 patients have been randomized (43 MGN1703, 16 placebo). Median PFS from start of maintenance was not different with 2.8 vs 2.7 months, however the HR was 0.56 (CI 95%: 0.29-1.08; p=0.069) in favor of MGN1703, due to a small favorable subgroup with long-term PFS (20% vs 0% at 9 months; p=0.006). Total PFS from beginning of induction chemotherapy including maintenance was significantly improved: HR 0.49 (CI 95%: 0.25-0.94), p=0.029. After a median follow-up of 13 months 66% of patients are still alive (67% vs 62%), therefore survival data are still preliminary (HR 0.79; CI 95%: 0.3-2.1) and will be mature at the meeting. Activation of cellular immune function as indicated by significant increase of CD14 + CD169 + monocytes was observed in all but one of the MGN1703 treated patients, while absent in all placebo patients. Treatment was well tolerated: 46.5% vs 31.3% of patients (MGN1703 vs placebo) had any drug-related adverse events (AE) and 20.9% vs 18.8% had AE with grade 3 or 4 (including hypertension, ileus, sepsis, sensory polyneuropathy, nausea/vomiting for MGN1703 and pain, popular exanthema for placebo). Conclusions: MGN1703 maintenance seems to prolong PFS in a subgroup of patients with disease control after induction chemotherapy vs placebo, and is associated with relative mild toxicity. This in an early signal in a selected and very limited patient population which supports further investigation. Predictive biomarkers are under evaluation to identify a potential subgroup which might have benefit from this TLR-9 MGN1703 maintenance. Clinical trial information: NCT01208194.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.3643
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
