Top Line: Is dual immune checkpoint inhibition better than durvalumab after chemoradiation for stage III NSCLC?
The Study: Chemoradiation followed by maintenance durvalumab is the standard treatment for locally advanced, stage III NSCLC without an actionable EGFR mutation. In SKYSCRAPER-03, 413 patients with stage III NSCLC treated with chemoradiation were randomized to receive either standard durvalumab or tiragolumab plus atezolizumab. Tiragolumab is a monoclonal antibody that inhibits TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is an inhibitory immune checkpoint receptor expressed on T cells and NK cells. TIGIT and PD-1 are often coexpressed, so the idea is that dual immune checkpoint inhibition could improve antitumor immune response. However, this combination did not significantly improve the primary endpoint of PFS in the PD-L1+ population (19.4 v 16.6 months) or the overall population (14.2 v 13.8 months). Overall survival was also similar between arms. Adverse effects were similar between arms.
TBL: In SKYSCRAPER-03, adding the TIGIT inhibitor tiragolumab to atezolizumab did not improve treatment outcomes compared to durvalumab for patients with stage III NSCLC. | Wakelee, Ann Oncol 2026
The Study: Chemoradiation followed by maintenance durvalumab is the standard treatment for locally advanced, stage III NSCLC without an actionable EGFR mutation. In SKYSCRAPER-03, 413 patients with stage III NSCLC treated with chemoradiation were randomized to receive either standard durvalumab or tiragolumab plus atezolizumab. Tiragolumab is a monoclonal antibody that inhibits TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is an inhibitory immune checkpoint receptor expressed on T cells and NK cells. TIGIT and PD-1 are often coexpressed, so the idea is that dual immune checkpoint inhibition could improve antitumor immune response. However, this combination did not significantly improve the primary endpoint of PFS in the PD-L1+ population (19.4 v 16.6 months) or the overall population (14.2 v 13.8 months). Overall survival was also similar between arms. Adverse effects were similar between arms.
TBL: In SKYSCRAPER-03, adding the TIGIT inhibitor tiragolumab to atezolizumab did not improve treatment outcomes compared to durvalumab for patients with stage III NSCLC. | Wakelee, Ann Oncol 2026