Exelixis, Inc. (NASDAQ:EXEL) today announced final results from BRIM7, an ongoing phase 1b clinical trial conducted by Roche and Genentech, Exelixis' collaborator and a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), of the BRAF inhibitor (BRAFi) vemurafenib in combination with the MEK inhibitor cobimetinib in patients with locally advanced/unresectable or metastatic melanoma carrying a BRAFV600 mutation. Antoni Ribas, M.D., Ph.D., a professor in the department of medicine at Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, presented the data during a plenary session today at the 10th European Association of Dermato-Oncology (EADO) Congress. The meeting is taking place from May 7-10, 2014, in Vilnius, Lithuania.
"Building on the previous data from the BRIM7 trial, these final results provide encouraging signs of clinical activity in BRAFi-naïve patients with the combination of cobimetinib and vemurafenib," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "We are pleased with the progress Roche has made in investigating cobimetinib, an Exelixis-discovered compound, in this patient population. People with this disease still urgently need improved treatment options, and we look forward to the top-line data from coBRIM, the ongoing phase 3 pivotal trial, anticipated later this year."
The phase 1b dose escalation study was designed to evaluate the safety and tolerability of cobimetinib in combination with vemurafenib. The dose escalation stage of the trial comprised 10 dosing cohorts of 3-6 patients and evaluated three different dosing schedules of cobimetinib in combination with twice daily administration of vemurafenib. After the maximum tolerated dose (MTD) was defined, two dose cohorts were expanded and additional patients with BRAF-mutated melanoma who were either BRAFi-naïve or vemurafenib-progressing patients were accrued.
As of October 1st, 2013, 129 patients had been treated, comprising 66 patients who had previously progressed while receiving vemurafenib and 63 patients who were BRAFi-naïve. Of the 63 BRAFi-naïve patients, 43 (68%) were previously untreated and 20 (32%) had been treated with agents other than a BRAFi. The majority of the patients had Stage IV, M1c melanoma at the time of enrollment (vemurafenib-progressors 82%, BRAFi-naïve 70%). The median duration of follow-up in vemurafenib-progressor and BRAFi-naïve patients was 6.3 and 12.7 months, respectively.
The final results of the exploratory secondary endpoints of BRIM7 showed anti-tumor activity for the combination of cobimetinib and vemurafenib. In BRAFi-naïve patients>
The most common adverse events (AEs) regardless of attribution to study treatment in the 129 patients treated to date were non-acneiform rash, diarrhea, fatigue, photosensitivity/sunburn, liver laboratory abnormalities and nausea. The most common (all Grade; ≥ Grade 3) AEs in BRAFi-naïve patients were non-acneiform rash (87%; 14%) diarrhea (83%; 8%), fatigue (70%; 10%) photosensitivity/sunburn (67%; 3%), liver laboratory abnormality (67%, 19%) and nausea (57%; 3%). The most common (all Grade; ≥ Grade 3) AEs in vemurafenib-progressor patients were diarrhea (47%; 3%), nausea (33%; 3%), non-acneiform rash (33%; 2%), fatigue (27%; 2%) and liver laboratory abnormality (33%; 6%). Most adverse events were mild to moderate in severity. Permanent discontinuation of vemurafenib, cobimetinib or the combination due to AEs was infrequent, and occurred in 5% (vemurafenib), 2% (cobimetinib) and 2% (combination) of the vemurafenib progressing patients and 6% (vemurafenib), 5% (cobimetinib) and 3% (combination) of the BRAFi-naïve patients.