Entry Detail
| General information | |
| Database: | DB00077 |
| Objective: | A histologyindependentphase 2 "basket" study of vemurafenib in BRAF V600 mutationpositive nonmelanoma cancers(including lung cancer). |
| Authors: | Hyman DM et al |
| Title: | Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. |
| Journal: | N Engl J Med |
| Year: | 2015 |
| PMID: | 26287849 |
| Trial Design | |
| Clinical Trial Id: | NCT01524978 |
| Agent: | vemurafenib |
| Target: | BRaf protooncogene serine/threonineprotein kinase |
| Cancer Type: | melanoma |
| Cancer Subtype: | BRAF V600mutant nonmelanoma cancers |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | vemurafenib+ cetuximab |
| Study Type: | a histologyindependentphase II "basket" study |
| Key Patients Feature: | A total of 122 patients with BRAF V600 mutationpositive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab, 20 patients with non small cell lung cancer |
| Biomarker: | BRAFmutant |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | single arm |
| Treatment Info: | A standard 3+3 doseescalation design (three to six patients per cohort and up to three dose levels tested) was used to establish the recommended (maximum tolerated) combination dose. An additional cohort of patients with colorectal cancer received vemurafenib and cetuximab at the recommended combination dose (960 mg of vemurafenib administered orally twice daily and an intravenous loading dose of 400 mg of cetuximab per square meter of bodysurface area, followed by a weekly intravenous dose of 250 mg per square meter), and the safety and efficacy were assessed. All other patients received vemurafenib alone at an oral dose of 960 mg twice daily. |
| Primary End Point: | the response rate; |
| Secondary End Point: | progression free and overall survival. |
| Patients Number: | 20 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 42% (95% confidence interval [CI], 20 to 67) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.3 months (95% CI, 3.5 to 10.8) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Safety was similar to that in prior studies of vemurafenib for melanoma |
| Conclusions: | BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non small cell lung cancer and in ErdheimChester disease and Langerhans'cell histiocytosis. The histologic context is an important determinant of response in BRAF V600mutated cancers. |