Tiragolumab

Overview

Tiragolumab (MTIG7192A; RG6058; RO7092284) is an investigational, fully human IgG1κ monoclonal antibody developed to treat cancer. It has primarily been evaluated intravenously with the anti-PD-L1 antibody atezolizumab, sometimes alongside chemotherapy. Clinical activity has varied substantially by tumor type: phase III benefit was demonstrated in esophageal squamous-cell carcinoma, whereas phase III trials in non-small-cell and small-cell lung cancers did not meet their primary efficacy endpoints. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

Tiragolumab targets TIGIT, an inhibitory immune-checkpoint receptor expressed on activated T cells, natural-killer cells and regulatory T cells. It blocks TIGIT binding to CD155/PVR, potentially restoring antitumor immune activity and complementing PD-L1 blockade. Tiragolumab has an active Fc region; translational and preclinical evidence suggests that Fc-receptor engagement can activate tumor-associated myeloid cells, reduce suppressive regulatory-T-cell programs and promote a less exhausted, more memory-like CD8-positive T-cell state. (pubmed.ncbi.nlm.nih.gov)

Efficacy

• Esophageal squamous-cell carcinoma — positive phase III result: In the Asian SKYSCRAPER-08 trial (461 patients), tiragolumab plus atezolizumab and chemotherapy improved median progression-free survival to 6.2 months, versus 5.4 months with placebo plus chemotherapy (HR 0.56). Median overall survival was 15.7 versus 11.1 months (HR 0.70), and independently assessed response rates were 59.7% versus 45.5%. (pubmed.ncbi.nlm.nih.gov)
• PD-L1-high non-small-cell lung cancer — negative confirmatory trial: The phase II CITYSCAPE study initially reported an objective response rate of 31.3% versus 16.2% and median progression-free survival of 5.4 versus 3.6 months for tiragolumab plus atezolizumab versus atezolizumab alone. However, the 521-patient phase III SKYSCRAPER-01 trial did not demonstrate statistically significant improvements in progression-free survival (7.0 vs 5.6 months; HR 0.78) or overall survival (23.1 vs 16.9 months; HR 0.87). (pubmed.ncbi.nlm.nih.gov)
• Extensive-stage small-cell lung cancer — negative phase III result: In SKYSCRAPER-02, adding tiragolumab to atezolizumab and carboplatin–etoposide did not improve progression-free survival (5.4 vs 5.6 months) or overall survival (13.1 months in both groups). (pubmed.ncbi.nlm.nih.gov)
• Locally advanced rectal cancer — preliminary phase II evidence: In NEOTERIC, atezolizumab plus tiragolumab after chemoradiotherapy produced a pathological complete-response rate of 35.7%, compared with 22.2% for atezolizumab alone. The small study used historical controls for its primary statistical comparison, limiting conclusions about tiragolumab’s incremental contribution. (pubmed.ncbi.nlm.nih.gov)
• Early solid-tumor study: In GO30103, tiragolumab monotherapy produced no confirmed responses, while combination treatment with atezolizumab produced response rates of 46% (6/13) in an immunotherapy-naive NSCLC cohort and 28% (5/18) in an esophageal-cancer cohort. (pubmed.ncbi.nlm.nih.gov)

Safety

Tiragolumab-containing regimens have generally shown safety profiles consistent with their individual components, although severe and fatal events have occurred.

• In SKYSCRAPER-01, grade 3–4 adverse events occurred in 41.2% with tiragolumab–atezolizumab and 33.8% with atezolizumab alone; there were four and two treatment-related deaths, respectively. (pubmed.ncbi.nlm.nih.gov)
• In SKYSCRAPER-08, serious adverse events occurred in 41% versus 39%, while treatment-related deaths occurred in 3% versus 1%. Frequent grade 3–4 events included neutropenia, leukopenia and anemia, largely in the context of chemotherapy. (pubmed.ncbi.nlm.nih.gov)
• In SKYSCRAPER-02, grade 3–4 immune-mediated adverse events occurred in 7.9% versus 7.7%, without a new safety signal. (pubmed.ncbi.nlm.nih.gov)
• First-in-human testing found no dose-limiting toxicities; common treatment-related events included fatigue with monotherapy and pruritus with combination therapy. (pubmed.ncbi.nlm.nih.gov)

Further reading

• SKYSCRAPER-08 phase III esophageal-cancer trial
• SKYSCRAPER-01 phase III NSCLC trial
• SKYSCRAPER-02 phase III small-cell lung-cancer trial
• CITYSCAPE phase II NSCLC trial
• First-in-human GO30103 study
• Mechanistic study of tiragolumab and Fc-receptor activity

Last updated: Sep 2026