Results, Setbacks

Roche’s big PhIII Tecentriq/Cotellic combo study for colon cancer fails, damaging Exelixis shares

The Tecentriq team at Roche/Genentech has run into another nasty setback. Their PD-L1 drug, combined with Cotellic, failed to make a significant difference on overall survival among colorectal cancer patients in the Phase III study. And the failure will have the biggest impact on Roche’s partner Exelixis, which had a lot riding on the IMblaze370 trial.

The key lesson for investigators: The vast majority of the patients in the study had microsatellite stable tumors, and they’re flagging the outcome here as fresh evidence that checkpoints in general won’t have much chance of success. They had been banking on early trial results indicating that adding a MEK inhibitor — Cotellic — could make a big difference. But that theory has gone down in flames.

Michael Morrissey

A number of analysts had earlier given this study — which used regorafenib (Stivarga) for the control arm — a good shot at success. There were no data in the release, which will likely be released at a later conference.

Exelixis’ shares had dropped by about 13% on afternoon trading.

The Phase III failure comes a month after the development partners were forced to halt enrollment of patients in the Phase II MODUL study after monitors tracked a string of deaths in a cohort of patients in the trial. One of those deaths was triggered by cardiogenic shock, which was linked to the combo.

Tecentriq has stumbled badly before in clinical trials. But as the third big PD-1/L1 to hit the market, it’s also had some notable successes. Most recently the FDA offered a quick decision on a triple combo using Tecentriq with Avastin and chemo for frontline lung cancer, where Merck has dominated with Keytruda as Bristol-Myers scrambled to be competitive.

In Q1 Merck hit $1.46 billion in Keytruda revenue, up 151% as the pharma giant continued to outpace Bristol-Myers on lung cancer. Bristol-Myers’ Opdivo, which got out to an early lead, scored $1.51 billion, leaving them vulnerable to dropping back to the number two spot. Roche, meanwhile, reported Q1 revenue of only $139 million for Tecentriq.

Roche, of course, will move along with 50 other studies for Tecentriq, but Exelixis will be forced to work through the stinging failure with significantly less to offer investors in terms of fresh catalysts to look to.

“We will continue to work with Genentech on the evaluation of cobimetinib’s potential in other tumor types, including in melanoma, in which there are two ongoing phase 3 pivotal trials,” said Exelixis CEO Michael Morrissey in a statement. “Separately, Exelixis remains focused on and committed to maximizing the potential of the cabozantinib franchise through our commercial activities and ongoing clinical development program evaluating the compound alone, or in combination with immune checkpoint inhibitors, across numerous tumor types.”


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