Array BioPharma Inc.'s Phase III trial planned for this summer in recurrent low-grade serous ovarian cancer (LGSOC) with its Novartis AG-partnered MEK inhibitor is one of a handful of late-stage studies expected to roll out this year.

"We're looking at five pivotal trials, all starting this year, across our two MEKs," said Ron Squarer, Array's CEO. "There could be more, based on data that's emerging at [the American Society of Clinical Oncology (ASCO) meeting] this year."

Called MILO (MEK Inhibitor in Low Grade Serous Ovarian Cancer), the ovarian cancer trial will test the efficacy and safety of MEK162 compared to standard chemotherapy treatments.

Specifically, the multinational, randomized trial will evaluate MEK162 against the physician's choice of standard chemo treatments in 300 patients with recurrent or persistent LGSOC, following at least one prior platinum-based chemo regimen and no more than three lines of prior chemo rounds. Progression-free survival is the primary endpoint, and the key secondary endpoint is overall survival.

Michael Needle, chief medical officer of Array, told BioWorld Today that diagnosing is fairly straightforward with LGSOC, with its "relatively mature-looking cells, as opposed to the wildly anaplastic, ugly malignant cells. The good news is that, overall, it has a relatively good prognosis. Although it doesn't typically respond to therapy, the time to progression tends to be lengthy, so younger women live longer. Once it relapses, it has a much shorter course."

Squarer called LGSOC "just an awful unmet need. After failing chemotherapy, and certainly after a relapse, there's very little you can do for a patient."

Array's payout is limited under the deal terms. "The money they spend and the money we spend gets pooled, and then we have a cap on how much we contribute," Squarer told BioWorld Today. "So, we pay a percentage, and then it's capped. Last year, we made a payment of just over $9 million, and the cap is in the same order of magnitude, same rough neighborhood as that."

Word of the MILO study follows Basel, Switzerland-based Novartis' disclosure that it will soon commence Phase III experiments with MEK162 in NRAS-mutant and BRAF-mutant melanoma.

Andrew Robbins, vice president of commercial operations for Array, noted that Novartis is scheduled to commence the NRAS melanoma trial "momentarily," and its data would be filed as a registration study, so that the ovarian trial's results would be part of a supplemental new drug application, if all goes well.

NRAS mutations represent about 20 percent of melanomas, and BRAF 40 percent, with longer duration of treatment for patients.

Novartis is "calling October 2014 as the data availability date," CEO Squarer said. "You could see MEK162 available for sale, in theory, as early as 2015. Certainly, it will be out there by 2016, based on this timeline." Use in other indications, then, would be added on, if the plan proceeds as hoped. "You get the proof for something, and then the product use grows with data," Squarer said.

Only the 'Beginning of the Story'

MEK162 is designed to inhibit MEK, a key protein in the Ras/Raf/MEK/ERK pathway that signals cancer cell proliferation and survival. The drug was licensed by Novartis in 2010, when the big pharma firm agreed to provide $45 million up front plus $422 million in potential milestone payments. (See BioWorld Today, April 21, 2010.)

Bracing for a big year, Boulder, Colo.-based Array raised $66 million late in 2012, agreeing to sell 18 million shares priced at $3.65 apiece, marking a 10 percent discount to the previous day's closing price of $4.06. The company should have enough to last into 2014, estimated Jefferies analyst Eun Yang in a research report. (See BioWorld Today, Nov. 12, 2012.)

Squarer, though, cited "a lot of moving parts to our cash situation." The company had "just about $90 million of cash on hand at the end of last quarter, and we haven't given guidance exactly how long that will last." The firm has nine partner-funded programs, eight at the Phase II stage, associated with more than $3 billion in potential milestone earnings. Array also is looking to partner geographically its programs in multiple myeloma and myelodysplastic syndromes. "Deals have been an important part of the story, and will be in the future," Squarer said.

With the multiple Phase III trials ahead, which include work by partner AstraZeneca plc, of London, with selumetinib in non-small-cell lung cancer (NSCLC), "progress in partnered programs will likely drive valuation upside from current levels," Yun wrote. The relationship with AstraZeneca goes all the way back to 2003. (See BioWorld Today, Dec. 19, 2003.)

At last year's ASCO meeting, researchers from the Dana-Farber Cancer Institute presented the results of a double-blind randomized Phase II trial that showed selumetinib plus chemo improved the overall response rate in NSCLC and more than doubled progression-free survival compared to chemo alone as second-line treatment. (See BioWorld Today, June 5, 2012.)

Wells Fargo analyst Matthew Andrews, initiating coverage in December 2012 with an "outperform" rating, wrote that "2013 is likely to be a key year for Array," thanks largely to the starts of the Phase III studies, "potentially helping [the company] gain broader investor visibility and credit, as it evolves to a strategically focused hematology/oncology" firm.

In oncology, Squarer said, "you either want to be first or you want to be best. [Novartis and AstraZeneca] really have chosen to develop the drugs differently, from the point of view of the tumor populations they've targeted, as well as the combinations of development strategies."

Whereas AstraZeneca tends to prefer single-agent biologics or those in combination with cytotoxic agents, Novartis "has a long history of looking for target combinations," he said. In melanoma, for example, the NRAS approach is single-agent, while the BRAF push adds the Raf inhibitor LGX818, Squarer said.

The five upcoming trials represent "not the end of the story," he added. "It's really the beginning."

AstraZeneca, Squarer said, "is running almost 50 trials, and Novartis is running certainly over a dozen company-sponsored trials, and we expect them to announce more trials on an ongoing basis." ASCO is expected to bring data in uveal melanoma that could spark more Phase III explorations. Array has an asthma program in the wings as well.

Array's stock (NASDAQ:ARRY) closed Tuesday at $5.24, down 56 cents.