Dive Insight:

After initial successes last decade, drugmakers have had difficulty developing new ways of training the immune system to attack cancers, and have relied instead on chemo and other types of medicines to broaden immunotherapy’s reach. While Bristol Myers Squibb won approval of a new immunotherapy earlier this month, other once high-profile drugs from companies like Incyte and Nektar Therapeutics have fallen short.

Expectations are high that immunotherapies aimed at TIGIT might be different. Over the past several years, Roche, Merck & Co., GlaxoSmithKline, Bristol Myers and Gilead have each either developed or acquired such drugs. Propelled by promising, early results from Roche and Merck, TIGIT inhibitors are now some of the most closely watched research programs in cancer drug development.

Roche, in particular, is counting heavily on tiragolumab’s success. The company has launched nine pivotal trials, four of which are expected to produce results in 2022. Earlier this year, CEO Bill Anderson said the company was betting tiragolumab combinations would help Roche “reclaim a leadership position” in immunotherapy, an area in which it trails Merck.

The trial results disclosed Wednesday are therefore a disappointment for Roche and a warning for other TIGIT drug developers. They’re the first Phase 3 study results for a TIGIT-blocking drug, and the first failure.

There are important caveats, however. For instance, Roche’s drug was tested in extensive-stage small cell lung cancer, an aggressive form of the disease that immunotherapies have had difficulty treating. Though a regimen of Tecentriq and chemotherapy improved survival and was approved for small-cell lung cancer in 2019, other drugs from Bristol Myers and Merck failed and were pulled from the market. Immunotherapy’s greatest success has come in non-small cell lung cancer, a much more common tumor type.

Roche also did not limit enrollment in it trials based on PD-L1 levels, a protein that’s associated with response to immunotherapy treatment. In an earlier test in non small cell lung cancer, tiragolumab was most effective in patients with high levels of PD-L1. Treatment didn’t add much, if any, benefit in those whose tumors expressed less of the protein.

Taken together, those factors made the study a “relatively high risk” trial with “low expectations,” wrote Chris Howerton, an analyst at Jefferies, in a note to clients. Howerton said he remains confident in the company’s ongoing Phase 3 study in non-small cell lung cancer, which is expected to produce results in the second quarter.