In a significant setback for TIGIT-targeted immunotherapy, Roche announced disappointing results from its phase 2/3 SKYSCRAPER-06 trial evaluating tiragolumab in advanced non-small cell lung cancer (NSCLC). The study found that the combination of tiragolumab with Tecentriq (atezolizumab) and chemotherapy performed worse than the control arm of Keytruda (pembrolizumab) with chemotherapy in previously untreated patients with locally advanced unresectable or metastatic non-squamous NSCLC.
The trial revealed inferior outcomes in both progression-free survival (PFS) and overall survival metrics for the tiragolumab combination compared to the standard-of-care Keytruda regimen. Dr. Levi Garraway, Roche's chief medical officer, acknowledged the disappointing results while emphasizing their contribution to understanding the anti-TIGIT pathway in cancer treatment.
Impact on Tiragolumab Development Program
This latest setback follows a complex development history for tiragolumab. The drug previously missed primary endpoints in two phase 3 lung cancer trials - SKYSCRAPER-1 in NSCLC and SKYSCRAPER-2 in extensive-stage small-cell lung cancer (ES-SCLC). However, subsequent follow-up data from SKYSCRAPER-1 had shown promising trends in overall survival, and positive results in a phase 1b/2 liver cancer trial had temporarily restored optimism for the program.
Roche currently maintains half a dozen phase 3 trials investigating tiragolumab across multiple indications, including other NSCLC settings, esophageal cancer, and liver cancer. The company had been targeting initial regulatory submissions by 2025 but is now reviewing potential changes to the ongoing development program in light of these results.
Broader Implications for TIGIT Inhibitor Class
The SKYSCRAPER-06 results add to mounting challenges for the TIGIT inhibitor drug class. Other companies have faced similar obstacles, with MSD recently discontinuing a phase 3 trial of vibostolimab (combined with pembrolizumab) in high-risk melanoma due to high discontinuation rates. Novartis also recently divested its rights to the TIGIT antibody ociperlimab to BeiGene, despite a previous $300 million upfront investment.
TIGIT, like PD-1/PD-L1, functions as an immune checkpoint that inhibits T-cell anti-tumor responses. While tiragolumab has been at the forefront of TIGIT inhibitor development, these recent results raise questions about the optimal approach to targeting this pathway in cancer treatment.
