Eli Lilly crashes out of KRAS race as toxicity sees it ditch phase 1 effort

Eli Lilly has quietly dropped its KRAS effort in cancer, leaving the door open for its rivals.

Late last year, the U.S. Big Pharma started a phase 1 of its KRAS inhibitor LY3499446 in patients with “advanced solid tumors” with the KRAS G12C mutation. KRAS inhibition became the most talked about cancer target last year, with Amgen causing waves with some impressive data in certain tumors (though not in all).

But nine months after starting that test, it looks as if Lilly is walking away from this potential marker, with its KRAS G12C inhibitor now “removed” from its pipeline, according to its latest R&D update posted today. A spokesperson for Lilly told FierceBiotech the reason was safety: "We observed unexpected toxicity in the clinic that precluded further development of LY3499446 and are winding down the trial."

If it is indeed now dead in the water, this lessens the potential competition for Amgen, which said in its financials this week that its KRAS drug AMG 510 (now known as sotorasib) is still on track to deliver data from a potentially pivotal phase 2 monotherapy study in patients with advanced non-small cell lung cancer in the coming months, despite ongoing pandemic disruptions to trials.

It also bodes well for Mirati, Trovagene (now Cardiff Oncology) and Boehringer Ingelheim, all of which have their own efforts in KRAS, with Mirati and Amgen leading the pack. Johnson & Johnson also has a KRAS drug in trials, but recently stopped recruiting.

The drug had been put under the guise of Loxo Oncology at Lilly, the new cancer R&D unit created last year after its buyout of Loxo.