| General information |
| Database: | DB00979 |
| Objective: | Thisphase I expansion study assessed safety, pharmacodynamic effects, and antitumor activity of RO4987655, a pure MEK inhibitor, in selected patients with advanced solid tumor |
| Authors: | Zimmer L, et al |
| Title: | Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RASRAF mutations. |
| Journal: | Clin Cancer Res. |
| Year: | 2014 |
| PMID: | 24947927 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | RO4987655
|
| Target: | MEK
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors with RASRAF mutations |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I expansion and pharmacodynamic study |
| Key Patients Feature: | pts with melanoma, non small cell lung cancer (non small cell lung cancer), and colorectal cancer |
| Biomarker: | ERK phosphorylation and Ki67 expression;BRAF and KRAS testing |
| Biomark Analysis: | Detailed mutational profiling confirmed RAS/RAF screening and identified additional aberrations (NRAS/nonBRAF melanomas; PIK3CA/KRAS colorectal cancer) without therapeutic implications. |
| Control Group Info: | single arm |
| Treatment Info: | oral RO4987655 administered continuously at recommended doses of 8.5 mg twice daily until progressive disease (PD). |
| Primary End Point: | safety, pharmacodynamic effects, and antitumor activity |
| Secondary End Point: | NA |
| Patients Number: | 95 |
| Trial Results |
| DLT_MTD: | Doselimiting toxicities (DLT) were blurred vision (n = 1) and elevated creatine phosphokinase (CPK; n = 3), all of which were reversible without treatment. The MTD of RO4987655 was 8.5 mg twice daily. |
| Objective Response Rate: | 23.6% in patients with BRAF V600mutant melanoma |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Doselimiting toxicities (DLT) were blurred vision (n = 1) and elevated creatine phosphokinase (CPK; n = 3), all of which were reversible without treatment. The MTD of RO4987655 was 8.5 mg twice daily. |
| Conclusions: | Safety profile of RO4987655 was comparable with other MEK inhibitors. Singleagent activity was observed in all entities except colorectal cancer. Evidence of target modulation and early biologic activity was shown among all indications independent of mutational status |