Roche's lung cancer gamble flames out as TIGIT digits come up short in phase 3

Roche’s gamble on anti-TIGIT drug tiragolumab in small cell lung cancer (SCLC) has flamed out. Having advanced tiragolumab in SCLC based on little more than a hunch, Roche has now revealed the drug failed to hit its co-primary survival endpoints in a phase 3 clinical trial.

Unusually, Roche moved tiragolumab into a phase 3 clinical trial in patients with extensive-stage SCLC on the strength of the efficacy seen in another indication. Roche had no randomized controlled data in SCLC, but the effect of giving tiragolumab and a checkpoint inhibitor to patients with non-small cell lung cancer (NSCLC) persuaded it to take “a calculated risk” and add the indication to its late-phase program.

The risky bet has failed. Adding tiragolumab to checkpoint inhibitor Tecentriq and chemotherapy failed to improve progression-free survival in the study of 490 people undergoing first-line treatment for SCLC, causing the trial to miss one of its co-primary endpoints. An interim analysis of data on overall survival, the other co-primary endpoint, found the planned final analysis was unlikely to hit statistical significance.  

Twin failures on the co-primary endpoints end Roche’s dream of using tiragolumab to enhance the effect of Tecentriq in SCLC. Analysts were braced for the setback given the lack of evidence on tiragolumab in SCLC.

“We sense there was widespread uncertainty going into the readout as the study was relatively high risk, but we do see a modest negative stock move today on a hit to sentiment,” analysts at Jefferies wrote in a note to investors. Roche shares fell when the market opened in Switzerland before quickly rallying back up toward the previous close of around 373 Swiss francs ($402). 

The bigger question is whether the data have read-throughs for the rest of the tiragolumab program and the broader, multicompany effort to target TIGIT. The SCLC study was free from red flags, with Roche reporting no new safety signals arose from the addition of tiragolumab to Tecentriq and chemotherapy, but that still leaves the question of whether the efficacy miss is a pointer to failures in other indications. 

Roche Pharmaceuticals CEO Bill Anderson shared his views on that question last month. “I think if that result comes in first and it was negative, I don’t think it undermines our confidence in the total program,” Anderson told analysts on a quarterly results conference call. The Jefferies analysts took a similar view after the SCLC failure, saying they “still have confidence” in the upcoming NSCLC data drop.