| General information |
| Database: | DB00192 |
| Objective: | Vemurafenib induces transient objective responses in half of BRAF V600E mutant melanoma patients and a median PFS of 5.3 months. PTEN loss and PI3K activation are common in BRAF mutant metastatic melanoma, and PI3K activation has been implicated as a cause acquired resistance to BRAF inhibitors. Thisphase I study tested the safety of combining the BRAF inhibitor, vemurafenib, with the PI3K inhibitor, BKM120, in patients with metastatic BRAF mutant melanoma. |
| Authors: | Algazi A.P, et al |
| Title: | a phase I trial of BKM120 combined with vemurafenib in BRAFV600E/k mutant advanced melanoma |
| Journal: | Journal of Clinical Oncology |
| Year: | 2014 |
| PMID: | http://meeting.ascopubs.org/cgi/content/abstract/32/15_suppl/9101 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | vemurafenib(BRAF inhibitor)+BKM120(PI3K inhibitor)
|
| Target: | BRAF and PI3K
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced BRAF(V600E/K) mut(+) melanoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | vemurafenib(BRAF inhibitor)+BKM120(PI3K inhibitor) |
| Study Type: | a phase I trial |
| Key Patients Feature: | patients with metastatic BRAF mutant melanoma. |
| Biomarker: | BRAF mutant |
| Biomark Analysis: | NA |
| Control Group Info: | single arm;Four BRAF inhibitor na ve patients+four BRAF inhibitor refractory patients |
| Treatment Info: | Vemurafenibna ve patients receive a single dose of oral BKM120 (d 7) then vemurafenib twice daily with BKM120 daily (starting on c1d1). Patients with prior progression on vemurafenib received both vemurafenib and BKM120 starting on c1d1 after a vemurafenib washout of at least 14 days. Serial biopsies prior to treatment, on cycle 1 day 15, and at progression were obtained for pharmacodynamics analysis in patients with visible or palpable tumors. 3 + 3 dose escalation was planned starting at vemurafenib 720 mg PO twice daily with BKM120 60 mg daily. |
| Primary End Point: | the safety, DLT, efficacy and Aes |
| Secondary End Point: | NA |
| Patients Number: | 8 |
| Trial Results |
| DLT_MTD: | Four BRAF inhibitor na ve patients and four BRAF inhibitor refractory patients were treated on study with vemurafenib 720 mg PO bid and BKM120 60 mg PO daily. Two BRAF inhibitor na ve patient experienced DLTs (myalgias, DRESS syndrome). One vemurafenib na ve patient was inevaluable due to noncompliance and had minimal exposure to study drug. Two of four BRAF inhibitor refractory patients experienced DLTs (myalgias, febrile neutropenia). One BRAF inhibitorresistant patient had a mixed response to treatment with a 35.9% reduction in target lesions and two new small subcutaneous lesions. |
| 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): | myalgias, febrile neutropenia, DRESS syndrome |
| Conclusions: | Combination therapy with vemurafenib and BKM120 in BRAFV600EK mutant melanoma was not tolerated in either BRAF inhibitor na?ve or BRAF inhibitor resistant patients. |