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Roche-Exelixis Study Fails as Mixed Year Continues For Cancer Drug Combos

Xconomy San Francisco — 

This year is a big one for cancer drug combinations, and the results, so far, have been mixed. Some combinations have shown they may change how certain cancers are treated. Others are falling flat in clinical testing. The latest to come up short is a regimen of Roche/Genentech and Exelixis cancer drugs that failed a big study in colorectal cancer this morning.

The Swiss drugmaker said its immunotherapy atezolizumab (Tecentriq) and Exelixis’s cancer drug cobimetinib (Cotellic) didn’t help extend the lives of colorectal cancer patients compared to Bayer’s regorafenib (Stivarga). The study, IMblaze370, enrolled 363 people with advanced colorectal cancer who had failed at least two rounds of chemotherapy. They got either atezolizumab-cobimetinib, atezolizumab alone, or regorafenib.

Roche and its South San Francisco-based Genentech unit appeared to blame the failure on the fact that 95 percent of the patients in the trial had microsatellite stable tumors. Colorectal cancer patients with such tumors haven’t responded to standalone treatment with checkpoint inhibitors like atezolizumab, and those on atezolizumab alone in IMblaze370 also didn’t see a benefit, the company said. The failure isn’t necessarily a surprise: Last month, Roche halted a mid-stage trial, Modul, testing the same combination in newly diagnosed patients after four study volunteers died. “While the failure in this difficult to treat population is disappointing, expectations had already been tempered,” wrote Jefferies analyst Ian Hilliker.

Checkpoint inhibitors are leading a wave of immunotherapies that are approved for several cancers. What has made them so enticing is just how long responses can last when they work—years, in some cases. The problem is they only work on a small fraction of patients, and it isn’t yet totally clear why. Combinations are seen as the key to expanding the reach of these drugs, and they’ve led to a slew of deals and alliances (Just this morning, for instance, Eli Lilly bought ARMO Biosciences for $1.6 billion to get its hand on an immunotherapy combination prospect). More than 1,000 trials are underway to find the right mix of drugs—including 21 Phase 3 trials of immunotherapies producing data in 2018.

So far, the results have produced highs and lows. Here’s a snapshot: A combination of Merck’s immunotherapy pembrolizumab (Keytruda) and chemotherapy helped cut the risk of death in half for patients with advanced lung cancer. Yet a highly anticipated drug combination, involving pembrolizumab and a drug from Incyte (NASDAQ: INCY) known as an IDO inhibitor, failed a Phase 3 study in skin cancer. Billions have been invested in IDO inhibitors over the past few years, and several companies dialed back their IDO trials after the Merck/Incyte study failed.  Details of more key studies will arise next month at the American Society of Clinical Oncology’s yearly meeting.

Shares of Exelixis, meanwhile, dipped about 9 percent. The company sells two drugs. One is cabozantinib, for kidney and thyroid cancers. The other is cobimetinib, what’s known as a MEK inhibitor and approved for skin cancer patients whose tumors have a specific genetic mutation. IMblaze370 marked a chance for Exelixis to expand cobimetinib’s reach into colorectal cancer as well. Array Biopharma (NASDAQ: ARRY) has been testing a rival MEK inhibitor in tandem with other treatments in a Phase 3 colorectal cancer study called BEACON.

Colorectal cancer is the third most common form of cancer and cancer related deaths in the U.S. An estimated 97,000 people will be diagnosed with the disease this year, according to the American Cancer Society.

Roche and Exelixis are still studying the atezolizumab-cobimetinib combination in two skin cancer studies.