“Array BioPharma’s (NASDAQ: ARRY) wholly-owned MEK inhibitor, binimetinib, and BRAF inhibitor, encorafenib, were showcased at the 2015 annual meeting of the American Society of Clinical Oncology (ASCO). At the meeting, preliminary data for the combination of binimetinib and encorafenib from a Phase 1b/2 dose escalation and expansion study in patients with BRAF-mutant melanoma who are BRAF inhibitor treatment naive were shared during an oral presentation. Results from the study indicate that binimetinib and encorafenib may be safely combined and show encouraging clinical activity consistent with MEK/BRAF inhibitor expectations in patients with BRAF-mutant melanoma who are BRAF inhibitor treatment naive. In addition, a differentiated safety profile relative to other MEK/BRAF inhibitor combinations is emerging in the dose range currently being used in the Phase 3 COLUMBUS trial. Array expects updated BRAF melanoma data from the ongoing Phase 2 combination trial (LOGIC-2) of binimetinib and encorafenib followed by the addition of a third targeted agent identified based on genetic testing at the time of progression will be submitted to a scientific conference later this year. LOGIC-2 utilizes the same dose of binimetinib and encorafenib currently being studied in the COLUMBUS trial.”
“In recent years, the FDA has approved new drugs for the treatment of advanced melanoma, which has presented new ways to treat the disease, according to a presentation at the American Academy of Dermatology annual meeting.
“ ‘In the last four years there have been four new drugs that have been FDA-approved for melanoma and what’s even more exciting is that they really speak to two new ways to treating melanoma,’ Allan C. Halpern, MD, MSc, chief of dermatology service at Memorial Sloan-Kettering Cancer Center, told Healio.com.
“The most recent FDA approval, in January, was the combination of a BRAF inhibitor and a MEK inhibitor for treating advanced melanoma.”
“As reported in The Lancet Oncology by Larkin et al, interim results of a safety study designed to reflect the spectrum of patients encountered in routine practice suggest that vemurafenib (Zelboraf) has a safety profile in patients with BRAF V600–mutated metastatic melanoma similar to that observed in the more select patient population included in registration trials. The study included patients with limited treatment options and sizable proportions with brain metastases, elevated lactate dehydrogenase (LDH), poor performance status, and age ≥ 75 years.”
Editor’s Note: The important takeaway from this story is that the drug vemurafenib can be used safely and effectively in some melanoma patients with poor prognoses, who may not fit the profile of patients typically enrolled in clinical trials to test the drug. To learn more about clinical trials and “targeted therapies” like vemurafenib, visit our Melanoma Basics.
“Half of melanoma patients with the BRAF mutation have a positive response to treatment with BRAF inhibitors, but nearly all of those patients develop resistance to the drugs and experience disease progression.
“Now, a new preclinical study published online ahead of print in the Journal of Clinical Investigation from Penn Medicine researchers found that in many cases the root of the resistance may lie in a never-before-seen autophagy mechanism induced by the BRAF inhibitors vermurafenib and dabrafenib. Autophagy is a process by which cancer cells recycle essential building blocks to fuel further growth. Block this pathway with the antimalarial drug hydroxycholoroquine [sic] (HCQ), the authors found, and the BRAF inhibitors will be able to do their job better…
“Based on these promising preclinical results, Dr. Amaravadi and his team have already launched a clinical trial for patients with advanced BRAF mutant melanoma to see how well-tolerated HCQ is with the BRAF inhibitor vemurafenib. ‘So far,’ he said, ‘we are seeing a benefit to patients and low toxicity.’ “