O-0012 - Updated Results of the Randomized Phase 2 Impact Trial: Maintenance with TLR-9 Agonist Mgn1703 Vs Placebo in Patients with Metastatic Colorectal Carcinoma (MCRC)

Abstract

Background: The PRIME study reported significantly improved progression-free survival (PFS) and overall survival (OS) with panitumumab + FOLFOX vs FOLFOX in patients with WT RAS (exons 2, 3 and 4 of KRAS and NRAS) mCRC in a prospective-retrospective analysis (unpublished data). The PEAK study, presented here, was an estimation study of the treatment effect of FOLFOX6 + panitumumab or bevacizumab in 1st-line wild-type (WT) KRAS mCRC. Methods: This prospective-retrospective analysis was designed to assess the effect of FOLFOX6 + panitumumab or bevacizumab on PFS (primary endpoint) and OS in WT RAS (exons 2, 3 and 4 of KRAS and NRAS) mCRC in the PEAK study. WT KRAS exon 2 tumors were required for study entry. Transgenomic SURVEYOR/WAVE™ analysis and bidirectional Sanger sequencing were conducted independently in banked specimens to detect mutations in KRAS exon 3 (codons 59/61), exon 4 (codons 117/ 146); NRAS exon 2 (codons 12/13), exon 3 (codons 59/61), exon 4 (codons 117/146); BRAF exon 15 (codon 600). Results: Of the 285 WT KRAS (exon 2) mCRC patients randomized, 278 received treatment. The RAS ascertainment rate is currently 75%. For patients with WT RAS, treatment HRs (pmab:bev) were 0.63 (95% CI, 0.43-0.94; p = 0.02) for PFS and 0.55 (95% CI, 0.30-1.01; p = 0.06) for OS (Table). Worst grade 3-5 adverse event rates were consistent with the primary analysis. Conclusion: PFS and OS HRs favored panitumumab + FOLFOX6 relative to bevacizumab + FOLFOX6 in this 1st-line estimation study in WT RAS mCRC, suggesting that activating RAS mutations appear to be predictive for panitumumab treatment effect. Safety profiles for both arms were consistent with previously reported studies.