BioPharma, Pharma

Closely watched Roche drug fails a second pivotal test in lung cancer

Roche reported that its drug tiragolumab failed to achieve one of two main goals of a Phase 3 study in non-small cell lung cancer. The antibody is designed to block TIGIT, a checkpoint protein that has been a hot target for pharmaceutical companies looking for a way to broaden the reach of cancer immunotherapy.


An experimental Roche drug that’s part of a closely watched class of new cancer immunotherapies has failed one of two main goals in a pivotal test in lung cancer. The disappointing results come less than two months after the drug, tiragolumab, failed a separate Phase 3 test in an aggressive form of lung cancer that has spread.

The Roche drug is an antibody designed to bind to and block TIGIT, a so-called checkpoint protein that keeps immune cells from attacking cancer cells. Blocking it is hoped to offer a new way to kickstart the immune system into action against cancer, and several big pharma companies have struck deals to join the TIGIT chase. But Roche’s latest failure with tiragolumab raises questions about the drug and the TIGIT target.

Roche has been testing tiragolumab in combination with Tecentriq, the company’s already approved blockbuster cancer immunotherapy. Tecentriq is also a checkpoint inhibitor but it addresses PD-L1, a protein that’s found in abundance on the surface of some cancer cells. The drug’s approved indications include non-small cell lung cancer and small cell lung cancer. By combining tiragolumab and Tecentriq to block two checkpoint proteins, Roche aims to overcome the ability of cancers to suppress the immune system and offer a way to restore the immune response.

The preliminary data announced Wednesday are from a Phase 3 study testing tiragolumab as a treatment for advanced non-small cell lung cancer that has spread and cannot be removed surgically. The study enrolled 534 patients randomly assigned to receive tiragolumab plus Tecentriq, or a placebo and Tecentriq.

According to Roche, the combination of checkpoint inhibitors did not help patients live longer without the cancer worsening, one of two main goals of the Phase 3 study. Roche said that with this first analysis, it’s too early to determine whether the drug met the study’s second main goal of improving overall survival of patients. Nevertheless, the company noted numerical improvements on both measures.

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“While these results are not what we hoped for in our first analysis, we look forward to seeing mature overall survival for this study to determine next steps,” Levi Garraway, Roche’s chief medical officer and head of global product development said in a prepared statement. “We continue to believe that TIGIT may have a role in cancer treatment and we will share additional results from our tiragolumab program as they emerge.”

Despite the disappointing early results, Roche said that the study will continue until the next planned analysis. So far, the drug has been well tolerated by patients and no new safety signals were reported. Roche plans to present further analysis of the data at an upcoming medical meeting.

Tiragolumab’s clinical trial failure in March was in a Phase 3 study testing the anti-TIGIT drug in combination with Tecentriq as a first-line treatment for extensive-stage small cell lung cancer. Roche reported at the time that the drug did not meet the goal of progression-free survival, one of two main goals of the Phase 3 study. At an earlier interim analysis, tiragolumab had failed to meet the other main goal of overall survival.

The potential for TIGIT inhibitors to broaden the reach of cancer immunotherapy has drawn the interest of several pharmaceutical companies. Nearly a year ago, Bristol Myers Squibb paid $200 million up front for global rights to Agenus’s TIGIT-blocking drug, AGEN1777. Soon after, GlaxoSmithKline joined the TIGIT chase, paying $625 million to kick off an alliance with iTeos Therapeutics and its early-stage TIGIT-targeting drug EOS-448. Gilead Sciences is in the TIGIT hunt via an alliance with Arcus Biosciences. Last fall, Gilead paid Arcus $725 million as it exercised options on three of its partner’s clinical-stage programs, including two TIGIT-blocking antibodies.

The clinical trial failures of Roche’s anti-TIGIT drug are having an effect on how investors view the rest of the drug class. Shares of Iteos fell more than 30% on Wednesday; Arcus’s stock price sank more than 29%.

[Updated 5/12/2022. The following two paragraphs added with analyst comments.] William Blair analyst Matt Phipps sees the failures of tiragolumab as dimming the prospects of success for others in the TIGIT field. In a Thursday research note, he wrote that it’s difficult to read much into the numerical improvements Roche reported for the co-primary endpoints of the study without more details about how those endpoints were powered. As for Roche’s hope to salvage a better result from a readout of overall survival (OS) data, Phipps noted that those outcomes have occurred when comparing an immunotherapy to chemotherapy or kinase inhibitors—there is no precedent for such results when comparing two immunotherapies.

“Ultimately, while there remains a possibility that an improvement in OS may be observed in the trial, we believe the odds of this outcome are now slim following this interim analysis, throwing water on the idea of TIGIT being the next validated checkpoint target,” Phipps said.

Photo: Giuseppe Aresu/Bloomberg, via Getty Images