Clinical Trials

Date: 2016-04-01

Type of information: Halting of the trial

phase: 3

Announcement: halting of the trial

Company: Array BioPharma (USA) Novartis (Switzerland)

Product: binimetinib (MEK162)

Action mechanism:

• kinase inhibitor. MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which signals cancer cell proliferation and survival. MEK has been shown to be activated in several tumor types such as non-small cell lung cancer, melanoma, thyroid cancer, ovarian cancer, and, in particular, tumors with BRAF and NRAS mutations. Binimetinib (MEK162) is a small molecule MEK inhibitor that targets a key position in this pathway. This small molecule selective inhibitor of the kinases MEK1 and MEK2 has been licensed to Novartis in 2010.

Disease: recurrent low-grade serous ovarian cancer (LGSOC)

Therapeutic area: Cancer - Oncology - Rare diseases

Country:

Trial details:

Latest news:

• • On April 1, 2016, Array BioPharma announced  its decision to discontinue the MILO study, a Phase 3 trial of binimetinib for the treatment of patients with low-grade serous ovarian cancer. The decision to stop the study was made after a planned interim analysis showed that the Hazard Ratio for Progression Free Survival (PFS) crossed the predefined futility boundary. Top-line results from the study had been expected in 2017. Array will work with investigators to appropriately conclude the MILO study in a manner consistent with the best interest of each patient, while more detailed results will be shared with the scientific community in the future. All other ongoing studies of binimetinib, including the Phase 3 COLUMBUS (BRAF-mutant melanoma) and NEMO (NRAS-mutant melanoma) trials, are unaffected.
• •  On August 12, 2014, Array BioPharma reported results for full year of its fiscal year ending June 30, 2014 and provided pipeline updates. Array is planning for potential return of binimetinib. In 2010, Array entered into an agreement with Novartis under which Novartis received worldwide rights to the. In April 2014, Novartis and GSK announced a definitive agreement which included Novartis acquiring GSK's MEK inhibitor, Mekinist®. The transaction is subject to approval by GSK shareholders and closing conditions, including anti-trust approvals. If Novartis' binimetinib development and commercialization rights are returned to Array, Novartis must provide support for ongoing clinical studies as specified in our agreement. Three Phase 3 trials with binimetinib in advanced cancer patients 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 Novartis projected regulatory filing estimated in 2015. Array reported previously that Novartis has indicated it will continue to honor its obligations under the Array-Novartis agreement relating to binimetinib, including obligations relating to support for ongoing clinical trials.
• Binimetinib was featured at the 2014 American Society for Clinical Oncologists (ASCO) annual meeting in June. 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) was presented. The data from this Phase 1b/2 dose-escalation study conducted by Novartis in NRAS-mutant melanoma demonstrated an acceptable safety profile for most patients with promising preliminary antitumor activity. Additional patients are being enrolled in the trial and the dosing schedule for the combination is being optimized. 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.
• In addition, a 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 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.
• • On May 6, 2013, Array BioPharma has announced that it will initiate a global Phase 3 clinical trial in patients with recurrent low-grade serous ovarian cancer (LGSOC) during the summer of 2013. The study, called MILO (MEK Inhibitor in Low Grade Serous Ovarian Cancer), will evaluate the efficacy and safety of MEK162 compared to standard chemotherapy treatments and is designed for worldwide regulatory submissions, including with the FDA and the EMA. The multinational, randomized Phase 3 trial will evaluate MEK162 against physician's choice of standard chemotherapy treatments in 300 patients with recurrent or persistent LGSOC following at least one prior platinum-based chemotherapy regimen and no more than three lines of prior chemotherapy regimens. The primary endpoint is progression-free survival, and the key secondary endpoint is overall survival.
• Array invented MEK162 and licensed worldwide rights to develop and commercialize the drug to Novartis in April 2010. The MILO study follows a recent announcement by Novartis detailing plans to initiate Phase 3 trials of MEK162 in both NRAS- and BRAF-mutant melanoma and will be covered as part of the Novartis/Array co-development agreement under which costs are capped annually and in total for Array. There are 10 active or completed oncology clinical trials of MEK162 with plans to initiate at least six trials in 2013, including three Phase 3 trials, one each planned in LGSOC, NRAS-mutant melanoma and BRAF-mutant melanoma.

Is general: Yes