Roche Submits Clinical Application in China for Tiragolumab, a Novel Anti-TIGIT Monoclonal Antibody

On June 8, Roche’s clinical trial application for tiragolumab injection submitted in China was accepted by the Center for Drug Evaluation (CDE). Tiragolumab is a TIGIT monoclonal antibody.

TIGIT is expressed in various immune cells, including CD8+ T cells, CD4+ T cells, and NK cells, and serves as a specific negative regulator of the CD226 co-stimulatory receptor. CD155, which is highly expressed on the surface of tumor cells, is a high-affinity ligand for TIGIT. Upon binding to TIGIT on the surface of NK and T cells, it inhibits the cytotoxic activity of T cells against tumor cells.

TIGIT is one of the most promising and potential targets in cancer immunotherapy. Preliminary clinical results have shown that anti-TIGIT antibodies, either as monotherapy or in combination with anti-PD-1/PD-L1 antibody drugs, demonstrate a certain level of safety and antitumor efficacy, with combination therapy expected to exhibit synergistic enhancement effects. Currently, multiple clinical studies related to anti-TIGIT monoclonal antibody drugs are being conducted abroad, but no products have yet been approved.

Data from the Phase II CITYSCAPE study, presented orally by Roche at the ASCO 2020 conference, demonstrated that first-line treatment with tiragolumab in combination with Tecentriq significantly improved outcomes in patients with PD-L1-positive non-small cell lung cancer (NSCLC). At a median follow-up of 5.9 months, the tiragolumab plus Tecentriq arm showed a significantly higher objective response rate (ORR) compared to the placebo plus Tecentriq arm (31.3% vs. 16.2%), a significantly prolonged median progression-free survival (PFS) (5.4 vs. 3.6 months), and a 43% reduction in the risk of disease progression or death (HR=0.57; 95% CI: 0.37–0.90).

At a median follow-up of 10.9 months, the tiragolumab plus Tecentriq arm demonstrated a significantly improved objective response rate (ORR) compared with the placebo plus Tecentriq arm in the intent-to-treat (ITT) population (37% vs. 21%). In patients with high PD-L1 expression (TPS ≥50%), the ORR was significantly higher with tiragolumab plus Tecentriq (n=29) than with placebo plus Tecentriq (n=29) (66% vs. 24%). However, in patients with low PD-L1 expression (TPS 1%–49%), the ORR did not improve with tiragolumab plus Tecentriq (n=38) compared with placebo plus Tecentriq (n=39) (16% vs. 18%).

In terms of PFS, among the population with high PD-L1 expression, the tiragolumab + Tecentriq treatment group showed a significantly improved survival benefit compared to the placebo + Tecentriq group (immature vs. 4.11 months).

In terms of safety, the tiragolumab plus Tecentriq treatment group was well tolerated, with an overall safety profile similar to that of the placebo plus Tecentriq group. Immune-mediated adverse events were more common, mostly Grade 1/2, and manageable.

Currently, Roche’s Tecentriq has been approved in China for first-line treatment of extensive-stage small cell lung cancer, and a marketing application has been submitted for Tecentriq in combination with bevacizumab as first-line therapy for liver cancer.