| General information |
| Database: | DB00142 |
| Objective: | Inhibition of AKT with MK2206 has demonstrated synergism with anticancer agents. Thisphase 1 study assessed the MTD, DLTs, PK, and efficacy of MK2206 in combination with cytotoxic and targeted therapies. |
| Authors: | Molife LR, et al |
| Title: | Phase 1 trial of the oral AKT inhibitor MK2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. |
| Journal: | J Hematol Oncol. |
| Year: | 2014 |
| PMID: | 24387695 |
| Trial Design |
| Clinical Trial Id: | NCT00848718. |
| Agent: | MK2206
|
| Target: | AKT1 protein kinase
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | MK2206+ carboplatin/paclitaxel, docetaxel, or erlotinib |
| Study Type: | a phase I trial |
| Key Patients Feature: | Advanced solid tumor patients |
| Biomarker: | Circulating nucleic acids were analyzed for PIK3CA (exons 9 and 20), KRAS (exons 2 and 3), and BRAF (exons 11 and 15) mutations. |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received oral MK2206 45 or 60 mg (QOD) with either carboplatin (AUC 6.0) and paclitaxel 200 mg/m2 (arm 1), docetaxel 75 mg/m2 (arm 2), or erlotinib 100 or 150 mg daily (arm 3); alternative schedules of MK2206 135200 mg QW or 90250 mg Q3W were also tested. |
| Primary End Point: | MDT, DLT, PK, PD, PR, SD, and Aes |
| Secondary End Point: | NA |
| Patients Number: | 72 |
| Trial Results |
| DLT_MTD: | MTD of MK2206 (N = 72) was 45 mg QOD or 200 mg Q3W (arm 1); MAD was 200 mg Q3W (arm 2) and 135 mg QW (arm 3). DLTs included skin rash (arms 1, 3), febrile neutropenia (QOD, arms 1, 2), tinnitus (Q3W, arm 2), and stomatitis (QOD, arm 3). |
| Objective Response Rate: | NA |
| Disease Control Rate: | Two patients with squamous cell carcinoma of the head and neck (arm 1; Q3W) demonstrated a complete and partial response (PR); additional PRs were observed in patients (1 each) with melanoma, endometrial, neuroendocrine prostate, non small cell lung cancer, and cervical cancers. Six patients had stable disease more than and equal to 6 months. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | MTD of MK2206 (N = 72) was 45 mg QOD or 200 mg Q3W (arm 1); MAD was 200 mg Q3W (arm 2) and 135 mg QW (arm 3). DLTs included skin rash (arms 1, 3), febrile neutropenia (QOD, arms 1, 2), tinnitus (Q3W, arm 2), and stomatitis (QOD, arm 3). |
| Conclusions: | MK2206 plus carboplatin and paclitaxel, docetaxel, or erlotinib was welltolerated, with early evidence of antitumor activity. |