Roche posts 'impressive' TIGIT combo lung cancer data, but trial deaths weigh down shares

New follow-up data for Roche’s Tecentriq-tiragolumab combination therapy in certain lung cancer patients have analysts sighing in relief that the anti-TIGIT element appears to be pulling its weight, but two deaths in the combination arm hit the company's shares Friday morning.

TIGIT, or T-cell immunoreceptor with immunoglobulin and ITIM domain, is a promising new target for cancer immunotherapy and is upregulated by immune cells including activated T cells, natural killer cells and regulatory T cells.

Roche has already posted some early data from a phase 2 trial, known as CITYSCAPE, at the American Society of Clinical Oncology (ASCO) cancer conference last year. Here, it showed its approved PD-L1 blocker, Tecentriq, combined with its experimental anti-TIGIT antibody tiragolumab shrank tumors in 31% of patients with metastatic lung cancer—twice as many patients as Tecentriq alone.

Now, we have much longer follow-up data from CITYSCAPE, which followed patients for a median of 2.5 years and “continued to show an improvement” in the intention-to-treat (ITT) population of 67 patients, driven by the PD-L1-high population.

In that ITT population, the combo therapy reduced the risk of disease worsening or death (i.e., progression-free survival) by 38% and improved overall response rates (ORR) at 38.8% compared with 20.6% for Tecentriq alone.

A predefined exploratory analysis in the PD-L1-high population showed a 71% reduction in the risk of disease worsening or death (median PFS was 16.6 vs. 4.1 months) and a clinically meaningful improvement in ORR (69% vs. 24.1%) with the combo compared with Tecentriq alone.

Roche also saw improved overall survival (OS), a secondary endpoint of the study but a golden data point in all cancer tests, seeing this in the ITT population, which was driven by the PD-L1-high population.

RELATED: ASCO: Roche's closely watched TIGIT combo shows 2 checkpoint inhibitors could be better than one

After 2.5 years, median OS was 23.2 vs. 14.5 months in the ITT population. The exploratory data in the PD-L1-high population showed a “clinically meaningful” OS improvement. The median was not reached for the tiragolumab regimen but “is projected to be greater than 30.3 months based on the lower confidence interval.”

Safety data weren't clean, however, as there were two grade 5 events—which in trial speak means deaths—specifically both from the combo arm of the trial. The two treatment-related deaths were the results of pyrexia—or fever—and infection, according to detailed data presented at the European Society for Medical Oncology Immuno-Oncology virtual congress. Shares were off nearly 1% in early premarket trading on this update, taking the shine off the data.

There have also been some concerns after ASCO 2020 that perhaps it was more that Tecentriq underperformed, rather than tiragolumab adding something special. But analysts at Jefferies said the updated follow-up data “should allay concerns the benefit initially reported was driven by underperformance of Tecentriq.”

A phase 3 trial program is already underway, with data set to start coming in from next year. The phase 2 follow-up data “should build confidence in ongoing tiragolumab phase 3 trials,” Jefferies added, highlighting the SKYSCRAPER-01 trial in PD-L1-high non-small cell lung cancer, with data expected later in 2022, “as a blockbuster opportunity.”

“These encouraging results suggest that combining anti-TIGIT and anti-PD-L1 cancer immunotherapies such as tiragolumab and Tecentriq could potentially represent a novel approach to address unmet needs in cancer,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of global product development.

“With tiragolumab, we have the largest and most advanced anti-TIGIT clinical program, and we look forward to the results of our phase 3 trials in lung cancer and other challenging tumor types.”

Roche is fighting with Merck—and, further back, Bristol Myers Squibb—to make TIGIT work big in cancer, with checkpoint inhibitor combos appearing to be the way to go for both pharmas.