Roche’s first TIGIT data points to benefit when added to Tecentriq

There had been high expectations for the first clinical data from Roche’s TIGIT-targeting antibody tiragolumab, developed as a companion drug to Tecentriq, and the results didn’t wholly disappoint.

The phase 2 CITYSCAPE trial showed that the combination of tiragolumab and PD-L1 inhibitor Tecentriq (atezolizumab) was able to improve the objective response rate and progression-free survival compared to Tecentriq alone as a first-line non-small-cell lung cancer (NSCLC) treatment.

The study provides a clear proof-of-concept for combining PD-1/PD-L1 inhibitors with anti-TIGIT drugs, which will be a boost to the growing number of companies developing drugs against the new immuno-oncology target such as Merck & Co/MSD, Bristol-Myers Squibb and Astellas.

Questions were raised about the results though, as Tecentriq failed to move the needle as a first-line NSCLC therapy on its own, with some observers arguing that the combination set a low hurdle to overcome.

Nevertheless, the top-line results suggest Tecentriq/tiragolumab could be an addition to the cancer immunotherapies available for this type of cancer.

Looking at the numbers released in an abstract ahead of the virtual ASCO congress due to start later this month, tiragolumab plus Tecentriq produced an ORR of 31.3% after 5.6 months’ follow-up, compared to 16.2% for Tecentriq on its own. PFS came in at 5.4 months and 3.6 months, respectively, in 135-patient trial.

There were also better results from a look at the subgroup of patients whose tumours expressed higher levels of the PD-L1 biomarker. In these subjects, the combination had an ORR of 55.2% compared to 17.2% for Tecentriq alone.

The combination as also well tolerated, said Roche, with similar rates of grade 3 or greater adverse events to Tecentriq monotherapy, which suggests tiragolumab wasn’t adding much to the side-effect burden.

Roche is hoping that tiragolumab could help unlock the first-line NSCLC treatment market for Tecentriq and help capture market share from Merck’s $12bn blockbuster Keytruda (pembrolizumab), which dominates the category.

Some analysts were, however, looking for a greater impact from the TIGIT/PD-L1 combination on response rates, suggesting that the combination might struggle to displace Keytruda plus chemo, a go-to therapy for first-line NSCLC regardless of PD-L1 status.

Overall, however, the picture is positive, with the data backing up TIGIT as a target and the safety of tiragolumab as a drug.

Roche is certainly investing in the programme, building its data set for the new drug with two phase 3 trials – SKYSCRAPER-01 and SKYSRCAPER-02 - as well as six earlier stage trials in other solid tumours and blood cancers.

SKYSCRAPER-01 is comparing tiragolumab/Tecentriq against Tecentriq monotherapy in previously-untreated, PD-L1-positive NSCLC, while SKYSCRAPER-02 is comparing triple therapy with tiragolumab/ Tecentriq and chemo to Tecentriq/chemo alone in extensive-stage small cell lung cancer (ES-SCLC).