Exelixis, Inc. (NASDAQ:EXEL) announced the presentation of new data from clinical trials of cobimetinib in combination with other therapies to treat forms of advanced melanoma. Data from phase 1b trials of cobimetinib in combination with atezolizumab, and with atezolizumab and vemurafenib, respectively, form the basis for two Genentech-sponsored phase 3 pivotal trials anticipated to start in 2017. Additionally, data from a pooled analysis of the combination of cobimetinib and vemurafenib demonstrate the potential for the combination to deliver lasting clinical benefit.
The data are being presented at the Society for Melanoma Research 2016 Congress, which is being held November 6-9 in Boston. Cobimetinib, a selective MEK inhibitor discovered by Exelixis and now the subject of a worldwide collaboration agreement with Genentech, a member of the Roche Group, is the subject of seven abstracts at the meeting.
“Since its initial regulatory approval last year, cobimetinib has continued to generate encouraging data with the potential to broaden its utility as a key component of combination regimens to treat serious forms of cancer,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. “If confirmed in the pivotal trials planned to initiate next year, the cobimetinib/atezolizumab and triple-combination regimens described in data at this year’s Society for Melanoma Research Congresscould become important new therapeutic options for clinicians treating multiple forms of advanced melanoma.”
Pivotal Trial in BRAF Wild-Type Melanoma Planned Following Encouraging Phase 1b Data
In a plenary session at the SMR 2016 Congress today, Jeffrey R. Infante, M.D., Director of the Drug Development Program and Principal Investigator at Sarah Cannon Research Institute, Nashville, Tennessee will present results from the metastatic melanoma cohort of a phase 1b dose escalation trial of cobimetinib and atezolizumab, an anti-PDL1 antibody developed by Genentech, in patients with solid tumors. The primary objective of the trial is to determine the safety and clinical activity of the combination, and key eligibility criteria include ECOG Performance Status of 0 or 1, measurable disease per RECIST, and no prior anti-PD-1/PDL1 therapy.
As of the July 12, 2016 data cut-off, 22 patients with metastatic melanoma were evaluable for safety and efficacy, including 20 patients with non-ocular melanoma (10 each with BRAF wild type and BRAF V600-mutation positive disease) and two patients with ocular melanoma. Among the 20 non-ocular melanoma patients, the objective response rate (ORR) was 45 percent, with 9 partial responses, including 5 in BRAF wild-type patients. Median duration of response was 14.9 months (12.9, upper limit not yet reached) across 9 responders, and was not yet reached for the BRAF wild-type subgroup. Median progression-free survival (PFS) was 12 months across all non-ocular melanoma patients (15.7 months in BRAF wild-type and 11.9 months in BRAF mutation-positive patients). With a median follow-up of 18.9 months, median overall survival (OS) for the cohort had not been reached.
All patients in the cohort were evaluable for safety. In this phase 1b study, investigators reported the combination of cobimetinib and atezolizumab was generally well tolerated. Treatment-related Grade 3-4 adverse events (AEs) occurred in 59 percent of patients, and no treatment-related grade 5 AEs were reported.
Based on these results, Genentech plans to initiate a phase 3 pivotal trial of cobimetinib plus atezolizumab versus a PD-1 inhibitor in patients with previously untreated BRAF wild-type advanced melanoma next year.
Updated Results for Triple Combination of Cobimetinib, Vemurafenib and Atezolizumab Set Stage for TRILOGY Pivotal Trial
Also in a plenary session today, Ryan Sullivan, M.D., Instructor in Medicine at Harvard Medical School and Member of the Cancer Immunology and Melanoma Programs atDana-Farber Cancer Institute will present results from the phase 1b trial of cobimetinib, vemurafenib and atezolizumab in patients with BRAF V600 mutation-positive metastatic melanoma. The primary objective of the trial is evaluation of the safety and tolerability of the triple combination, with secondary endpoints including PFS, OS, ORR, best overall response, and duration of response, among others.
Patients in the trial receive the triple combination of cobimetinib, vemurafenib and atezolizumab following a 28-day run-in cycle of cobimetinib plus vemurafenib. As of theJune 15, 2016 data cut-off, 30 patients with previously untreated BRAF V600 mutation-positive advanced melanoma who received at least one dose of atezolizumab were evaluable for safety and efficacy. Responses were seen in 24 of 29 patients (83 percent) evaluable for efficacy, including three complete responses and 21 partial responses. Median duration of response and median PFS were not estimable due to limited follow-up time; the majority of patients continued to respond at time of data cut-off (median follow-up of 5.6 months).
Investigators reported the triple combination of cobimetinib, vemurafenib and atezolizumab was generally well tolerated in this investigational study. Median safety follow-up was 3.9 months (range 0.7-16.8 months). Grade 3-4 AEs were seen in 40 percent of patients that received the triple combination, and all AEs resolved after appropriate intervention. No unexpected AEs, grade 5 AEs or atezolizumab-related serious AEs occurred.
In early 2017, Genentech and Roche plan to initiate TRILOGY (NCT02908672), a pivotal placebo-controlled phase 3 trial evaluating the combination of cobimetinib, vemurafenib and atezolizumab compared to cobimetinib, vemurafenib and placebo. TRILOGY will enroll an estimated 500 patients with previously untreated BRAF V600 mutation-positive metastatic melanoma. The primary endpoint of TRILOGY is PFS as determined by the investigator, and secondary endpoints include PFS by independent review committee, OS, ORR, duration of response, safety and pharmacokinetics.
Efficacy of Long-Term Cobimetinib and Vemurafenib Detailed in Poster Session
Also at the SMR 2016 Congress, Prof. Grant McArthur, Co-chair of the Melanoma and Skin Service at Peter MacCallum Cancer Centre (Melbourne, Victoria, Australia) and colleagues presented a poster demonstrating the continuing benefit across all patient subgroups of the combination therapy of cobimetinib and vemurafenib versus vemurafenib monotherapy as assessed in the coBRIM phase 3 pivotal trial that formed the basis for the combination’s regulatory approval to treat BRAF V600-mutation positive advanced melanoma. The percentage of patients alive at three years was 37.4 percent for cobimetinib and vemurafenib, as compared to 31.1 percent for patients treated with vemurafenib plus placebo. Median overall survival was 22.5 months for the combination versus 17.4 months for vemurafenib alone. The safety profile was similar to what was reported previously, and discontinuation rates due to AEs were below 20 percent. (Original Source)
Shares of Exelixis are currently trading at $12.27, up $0.36 or 3.02%. EXEL has a 1-year high of $15.58 and a 1-year low of $3.55. The stock’s 50-day moving average is $13.08 and its 200-day moving average is $9.13.
On the ratings front, Exelixis has been the subject of a number of recent research reports. In a report issued on November 4, Cowen analyst Eric Schmidt reiterated a Buy rating on EXEL. Separately, on November 3, Deutsche Bank’s Andrew Peters initiated coverage with a Buy rating on the stock and has a price target of $17.
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Eric Schmidt and Andrew Peters have a yearly average return of 12.4% and a loss of 22.0% respectively. Schmidt has a success rate of 41% and is ranked #176 out of 4162 analysts, while Peters has a success rate of 35% and is ranked #3928.
Overall, 6 research analysts have given a Buy rating to the stock. When considering if perhaps the stock is under or overvalued, the average price target is $16.50 which is 38.5% above where the stock closed last Friday.
Exelixis, Inc. is a biopharmaceutical company, which engages in the developing and commercializing small molecule therapies for the treatment of cancer. Its brands include COMETRIQ and cobimetinib. The company focuses on their proprietary resources and development and commercialization of cabozantinib.