| General information |
| Database: | DB00194 |
| Objective: | Gq/11 mutations are early oncogenic events in UM resulting in MAPK pathway activation. They demonstrated decreased viability in UM cell lines harboring Gq/11 mut with sel, a small molecule inhibitor of MEK1/2 |
| Authors: | Richard D. Carvajal, et al |
| Title: | Phase II study of selumetinib (sel) versus temozolomide (TMZ) in gnaq/Gna11 (Gq/11) mutant (mut) uveal melanoma (UM). |
| Journal: | J Clin Oncol |
| Year: | 2013 |
| PMID: | https://www.researchgate.net/publication/295572565_Phase_II_study_of_selumetinib_sel_versus_temozolomide_TMZ_in_gnaqGna11_Gq11_mutant_mut_uveal_melanoma_UM ev=auth_pub |
| Trial Design |
| Clinical Trial Id: | NCT01143402 |
| Agent: | selumetinib
|
| Target: | Dual specificity mitogenactivated protein kinase kinase
|
| Cancer Type: | melanoma |
| Cancer Subtype: | gnaq/Gna11 (Gq/11) mutant (mut) uveal melanoma (UM) |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a I6 center randomizedphase II study |
| Key Patients Feature: | patients (pts) with metastatic UM with a Q209 Gq/11 mut who have not received prior TMZ/DTIC |
| Biomarker: | a Q209 Gq/11 mutation |
| Biomark Analysis: | NA |
| Control Group Info: | temozolomide (TMZ) |
| Treatment Info: | hydsulfate sel 75 mg BID vs TMZ 150 mg/m2 daily for 5 days in 28day cycles (or DTIC 1000 mg/m2 q21 days) |
| Primary End Point: | progression free survival (PFS). |
| Secondary End Point: | overall survival (OS) and response rate (RR). |
| Patients Number: | 80 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Sel:RR 11%. TMZ:RR 0%.TMZ¡úSel:RR 0% |
| Disease Control Rate: | At interim analysis (9/25/12), 55 pts were evaluable with 45 progression events and 16 deaths. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Sel (n=27): median PFS 16 wks (95% CI 830.9), TMZ (n=28): median PFS 4 wks (95% CI 3.715), TMZ¡úSel (n=25): median PFS 8.1 wks (95% CI 715). |
| Median OS A vs. C: | Sel(n=27):median OS 11.8 months (95% CI 4.8not reached).TMZ:median OS 4.7 months (95% CI 4.314.3). |
| Adverse Event(agent arm): | 11/39 (28%) pts on sel experienced grade (gr) 3 toxicity (tox) manageable with dose modification (5 CPK elevation, 3 LFT elevation, 1 rash, 1 lymphopenia, 1 edema). |
| Conclusions: | Sel is the first drug to ever show improved clinical activity in UM relative to TMZ. Sustained target inhibition is observed with sel. Final results will be presented. |