On 30 March, Roche published a press release stating that the Phase III pivotal SKYSCRAPER-02 trial of its investigational immunotherapy tiragolumab, in combination with Roche’s FDA-approved programmed cell death protein (PD)-1 inhibitor, Tecentriq (atezolizumab) and carboplatin and etoposide chemotherapy, in 490 patients with extensive-stage small-cell lung cancer (ES-SCLC) had not met its co-primary endpoints of overall survival (OS) and progression-free survival (PFS). Despite this, Roche will continue to examine tiragolumab in the treatment of non-small cell cancer (NSCLC) in the Phase III pivotal trials SKYSCRAPER-01 and SKYSCRAPER-03.

SCLC constitutes around 10–15% of all lung cancers and is a subtype characterised by aggressive disease and a lack of therapeutic options, resulting in poor clinical outcomes for patients. The five-year survival rate for patients with localised SCLC is 27%, while for patients with regional or distant metastases, five-year survival rates recede to 16% and 3% respectively. As such, novel therapies are required to build upon the current standard of care for first-line treatment, Tecentriq and chemotherapy.

Tiragolumab is a monoclonal antibody that targets the inhibitory receptor T-cell immunoglobulin and ITIM domain (TIGIT), which is expressed on lymphocytes and suppresses the immune response to cancer. Because the TIGIT pathway is distinct but complementary to the PD-1 pathway, the combination of tiragolumab, Tecentriq and chemotherapy was hypothesised to restore the anti-cancer immune response. Despite a good safety profile, however, co-primary endpoints of OS and PFS were not met in the SKYSCRAPER-02 trial. The full data from this trial are to be presented at an upcoming medical meeting. In the meantime, Roche will turn its attention to tiragolumab in the treatment of NSCLC.

Novel data from the Phase II CITYSCAPE study shows the combination of Tecentriq + tiragolumab reduced the risk of death by 38% and improved overall response rates (ORR) by 18% (38.8% vs 20.6%) compared with Tecentriq alone. Based on positive results from this trial, tiragolumab was granted breakthrough therapy designation by the FDA for the first-line treatment of patients with metastatic NSCLC whose tumours have high PD-ligand 1 (PD-L1) expression and no EGFR or ALK genomic aberrations.

Given that tiragolumab is the only anti-TIGIT drug to be granted this designation, key opinion leaders believe this therapy is well-placed to penetrate the NSCLC market due its novel mechanism of action and combination with the well-established drug, Tecentriq. According to GlobalData’s patient-based NSCLC forecast, Tecentriq + tiragolumab sales in the US in the first-line setting are expected to reach $282m by 2029 if approved.