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Two Array-Invented MEK Inhibitors Showcased At ASCO
Six Phase 3 / Pivotal Trials with Array's MEK Inhibitors Advancing
BOULDER, Colo., June 2, 2014 /PRNewswire/ -- Two Array BioPharma-invented MEK inhibitors, binimetinib (MEK162) and selumetinib, were showcased at the 50th annual meeting of the American Society of Clinical Oncology (ASCO). At the meeting, preliminary data for the combination of binimetinib and CDK4/6 inhibitor LEE011 (discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals) from a Phase 1b/2 dose-escalation study conducted by Novartis in NRAS-mutant melanoma indicates the combination demonstrated an acceptable safety profile for most patients with promising preliminary antitumor activity. Additionally, preliminary data for selumetinib showed favorable clinical activity in pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs).
Array BioPharma Inc. (NASDAQ: ARRY) licensed worldwide rights to develop and commercialize binimetinib to Novartis in 2010 and licensed worldwide rights to develop and commercialize selumetinib to AstraZeneca PLC in 2003.
Three Phase 3 trials with binimetinib in patients with advanced cancer continue to enroll: NRAS-mutant melanoma (NEMO / NCT01763164), low-grade serous ovarian cancer (MILO / NCT01849874) and BRAF-mutant melanoma (COLUMBUS / NCT01909453). NRAS-mutant melanoma represents the first potential indication for binimetinib, with a projected regulatory filing from the NRAS-mutant melanoma study estimated to be in 2015. Three pivotal trials continue to advance with selumetinib in advanced cancer patients: second-line KRAS-mutant advanced or metastatic NSCLC (SELECT-1 / NCT01933932), differentiated thyroid cancer (ASTRA / NCT01843062) and metastatic uveal melanoma (SUMIT / NCT01974752). In addition, AstraZeneca announced that it is considering a new Phase 3 investment in first-line KRAS-mutant NSCLC. Uveal melanoma represents the first potential indication for selumetinib, with a projected regulatory filing in 2015.
Binimetinib and Novartis compound LEE011 in NRAS-mutant melanoma
The Phase 1b/2 study with binimetinib and Novartis CDK4/6 inhibitor LEE011 showed promising preliminary antitumor activity in NRAS-mutant melanoma patients. As of March 21, 2014, 22 patients were enrolled. Of 21 evaluable patients, seven achieved a partial response (33%, 3 confirmed, 4 unconfirmed) and 11 had stable disease (52%). Several patients experienced early tumor shrinkage with major symptomatic improvement; 12 patients remain on treatment (55%, duration 2 to 8 months). Common treatment-related adverse events included elevated creatine phosphokinase (CPK) and creatinine; skin, hematologic and gastrointestinal events; edema; and fatigue.
"NRAS-mutant melanoma has poor prognosis with no approved targeted therapies," said Kevin B. Kim, M.D., Associate Professor, Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center. "Simultaneous inhibition of MEK and CDK4/6 could suppress the activation of two major signaling pathways associated with NRAS mutations and may provide the benefits of additive efficacy over single-agent therapy."
Melanoma is the fifth most common cancer among men and the seventh most common cancer among women in the United States, with 76,000 new cases and over 9,700 deaths from the disease projected in 2014. Novel therapies that target the RAS/RAF/MEK/ERK pathway have a strong scientific rationale for activity in this disease, as melanoma is often characterized by activating mutations in BRAF (approximately 50% of patients) and NRAS (15% to 20% of patients). There are presently no approved therapies specifically targeting NRAS-mutant melanoma.
Selumetinib in NF1
A Phase 1 study with selumetinib showed early encouraging clinical activity in pediatric patients with NF1 and PNs. Eleven of 18 patients (61%) achieved a partial response, defined as a greater than or equal to 20% improvement. Common treatment-related adverse events included acneiform rash, asymptomatic CPK elevation, nausea, vomiting, diarrhea, abdominal pain and fatigue. All toxicities were reversible.
Binimetinib and Novartis compound BYL719 in RAS- or BRAF-mutant solid tumors
The Phase 1b study with binimetinib and Novartis PI3K inhibitor, BYL719, in patients with RAS- and BRAF-mutant solid tumors (over 10 tumor types) was presented, with encouraging preliminary antitumor activity in patients with KRAS-mutant ovarian cancer. Three out of four (75%) ovarian cancer patients achieved a partial response. In the overall study population, the most common dose-limiting toxicities and treatment‘related adverse events included gastrointestinal events and rashes.
About MEK, Selumetinib and Binimetinib
About Array BioPharma
SOURCE Array BioPharma