Shares of Array Biopharma Inc. (NASDAQ:ARRY) climbed 81 percent to close at $6.61 on Monday after the Boulder, Colo.-based company announced that the first part of its phase III COLUMBUS trial in BRAF-mutant melanoma met its primary endpoint, a good sign for the company's prospects of engaging with the growing market opportunity represented by MEK /BRAF inhibitors.

The statistically significant median progression-free survival benefit for patients treated with a combination of two Array drugs, the MEK inhibitor binimetinib and the BRAF inhibitor encorafenib, is 14.9 months vs. 7.3 months for Roche AG's Zelboraf (vemurafenib) alone. Global regulatory submissions for the new combination, to be handled by Array and its overseas partner Pierre Fabre SA, are planned for 2017.

"The data look impressive to us, indicating a potential best-in-class profile for ARRY's combination with potentially better tolerability and significantly longer median progression free survival as compared to approved combinations by Novartis and Roche," Leerink analyst Michael Schmidt wrote. "While the study just missed a secondary endpoint (comparison vs. encorafenib monotherapy), we think the approval probability is high, given the well established mechanism of MEK and BRAF inhibitor combinations."

On Sept. 1, Array announced FDA acceptance of a new drug application for binimetinib alone for the treatment of patients with advanced NRAS-mutant melanoma. The agency plans to hold an Oncologic Drugs Advisory Committee meeting ahead of the June 30 PDUFA date set for review of that application. An approval would lay the groundwork for treatment of the 15 percent to 20 percent of melanoma patients who have the NRAS mutation. (See BioWorld Today, Dec. 17, 2015.)

But with activating BRAF mutations present in about 50 percent of patients with metastatic melanoma, Array and others have sought to broaden their reach through combination therapies. Quarterly sales of other MEK/BRAF inhibitor combinations — such as Novartis AG's combination of Tafinlar (dabrafenib) and Mekinist (trametinib) and Roche AG's combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) — are on the rise, Array pointed out during a conference call held Monday to discuss the new top-line data.

"With global sales exhibiting quarter on quarter growth, these products are approaching $1 billion annual sales run rate including approximately $400 million in the U.S. alone," said Array's CEO Ron Squarer.

Array regained control of both binimetinib and encorafenib almost a year ago as part of Novartis AG's purchase of Glaxosmithkline plc's oncology business, an event which opened the door for Paris-based Pierre Fabre to license European, Asian and Latin American rights to both oral small-molecule candidates. It was unclear if Monday's top-line data report triggered any of the $425 million in milestone payments Pierre Fabre pledged to Array in that deal. Novartis remained on the hook for reimbursement of many of the costs related to trials for the candidates, including COLUMBUS, lightning Array's financial load. (See BioWorld Today, Nov. 17, 2015.)

In COLUMBUS, an acronym for "Combined LGX818 Used with MEK162 in BRAF Mutant Unresectable Skin Cancer," the company designed a two-part, international, randomized, open-label phase III trial to evaluate the efficacy and safety of the combination of encorafenib plus binimetinib to vemurafenib and encorafenib monotherapy. It was set up to enroll 921 patients with locally advanced, unresectable or metastatic melanoma with BRAF V600 mutation. Prior immunotherapy treatment was allowed.

In part 1 of the study – the part for which top-line results were reported Monday – 577 patients were randomized 1:1:1 to receive the combination of 450-mg encorafenib plus 45-mg binimetinib, 300-mg encorafenib alone, or 960-mg vemurafenib alone.

The primary endpoint was a PFS comparison of the binimetinib plus encorafenib combination vs. Zelboraf alone, determined based on tumor assessment by a blinded independent review committee. Secondary endpoints include a comparison of the PFS of encorafenib monotherapy to that of the combination and a comparison of overall survival for the combination to that of vemurafenib alone.

An analysis of a secondary endpoint comparing the PFS of patients treated with the combination to those treated with encorafenib alone showed a median of 14.9 months vs. 9.6 months with HR (0.75), [95 percent CI 0.56-1.00], p=0.051, which did not reach statistical significance.

Binimetinib was generally well-tolerated and the adverse events reported were consistent with prior binimetinib results in NRAS mutant melanoma patients.

The grade 3 and grade 4 adverse events reported in greater or equal to 5 percent of patients receiving binimetinib included increased creatine phosphokinase and hypertension.

Data from part 2 of the COLUMBUS trial are anticipated in mid-2017.