| General information |
| Database: | DB00141 |
| Objective: | a phase I study of MK2206 was conducted to investigate its safety, maximumtolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics (PDs), and preliminary antitumor efficacy. |
| Authors: | Yap TA, et al |
| Title: | Firstinman clinical trial of the oral panAKT inhibitor MK2206 in patients with advanced solid tumors. |
| Journal: | J Clin Oncol |
| Year: | 2011 |
| PMID: | 22025163 |
| Trial Design |
| Clinical Trial Id: | NCT00670488. |
| Agent: | MK2206
|
| Target: | AKT1 protein kinase
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I Safety, Pharmacokinetic, and Pharmacodynamic Study |
| Key Patients Feature: | Patients with advanced solid tumors |
| Biomarker: | phosphatase and tensin homolog (PTEN) loss |
| Biomark Analysis: | Phosphorylated serine 473 AKT, phosphorylated threonine 246 prolinerich AKT substrate 40, insulin cpeptide, cancer antigen 199 levels |
| Control Group Info: | single arm |
| Treatment Info: | Pts received MK2206 on alternate days. Paired tumor biopsies were mandated at the MTD for biomarker studies. PD studies incorporated tumor and hair follicle analyses, and putative predictive biomarker studies included tumor somatic mutation analyses and immunohistochemistry for phosphatase and tensin homolog (PTEN) loss. |
| Primary End Point: | MTD, safety, PK, PD and preliminary activity |
| Secondary End Point: | NA |
| Patients Number: | 33 |
| Trial Results |
| DLT_MTD: | Doselimiting toxicities included skin rash and stomatitis, establishing the MTD at 60 mg. Drugrelated toxicities included skin rash (51.5%), nausea (36.4%), pruritus (24.2%), hyperglycemia (21.2%), and diarrhea (21.2%). |
| Objective Response Rate: | NA |
| 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): | NA |
| Conclusions: | MK2206 was well tolerated, with evidence of AKT signaling blockade. Rational combination trials are ongoing to maximize clinical benefit with this therapeutic strategy. |