Entry Detail
| General information | |
| Database: | DB00179 |
| Objective: | Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors. |
| Authors: | R. Kefford, et al |
| Title: | Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors. |
| Journal: | J Clin Oncol |
| Year: | 2010 ASCO Annual Meeting |
| PMID: | http://meeting.ascopubs.org/cgi/content/abstract/28/15_suppl/8503 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | GSK2118436 |
| Target: | BRaf protooncogene serine/threonineprotein kinase |
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma and other solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a firsttime in human, dose escalationphase I/II study |
| Key Patients Feature: | patients with metastatic melanoma and other solid tumors. 61 pts(52 mut BRAF melanoma) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Pts were treated with oral GSK2118436 once to three times daily. Once safety was established in cohorts of 3 to 4 pts, cohorts were expanded to determine the optimal dose based on efficacy and tolerability. |
| Primary End Point: | the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy |
| Secondary End Point: | NA |
| Patients Number: | 61 |
| Trial Results | |
| DLT_MTD: | MTD has not yet been determined. 1 pt reported doselimiting toxicity of syncope (200 mg BID) and resumed reduced dosing. |
| Objective Response Rate: | NA |
| Disease Control Rate: | In pts with mut BRAF melanoma: exposurerelated decrease in FDGPET metabolic uptake was noted with 11/14 (79%) pts showing a decrease from baseline (range 5 to 100%). In pts with mut BRAF melanoma (without brain mets) 18/ 30 (60%) pts have a > 20% tumor decrease by RECIST at first restaging (89 wks). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | AEs included skin changes (23 pts, 1 gr 3), low grade cutaneous SCC (2 pts), headache (12 pts, 1 gr 3), nausea (11 gr 1), fatigue (9 gr 1), and vomiting (8 pts, 4 gr 2) |
| Conclusions: | MTD has not yet been reached. Clinical activity with minimal toxicity was observed at multiple dose levels in mut BRAF tumors. |