Roche Halts NSCLC Study After TIGIT Drug Falls Short Against Keytruda-Chemo

Roche announced on Thursday that it will discontinue the Phase II/III SKYSCRAPER-06 study due to disappointing results from its investigational anti-TIGIT antibody, tiragolumab. The drug failed to significantly improve survival rates in patients with non-small cell lung cancer (NSCLC).

The study, which included 524 participants with non-squamous NSCLC, aimed to evaluate the effectiveness of a combination of tiragolumab and Roche’s PD-L1 blocker, Tecentriq (atezolizumab), as a first-line treatment. The control group received Merck’s Keytruda (pembrolizumab) combined with chemotherapy.

During the primary analysis, the data showed that the tiragolumab regimen exhibited “reduced efficacy” in progression-free survival (PFS) compared to the Keytruda combination, with a hazard ratio of 1.27 favoring the Keytruda arm. Additionally, the overall survival (OS) data, which were not fully mature at the time, also leaned towards Merck’s Keytruda with a hazard ratio of 1.33.

In terms of safety, the SKYSCRAPER-06 study found no new safety concerns, with adverse events aligning with previously known data for both tiragolumab and Tecentriq.

Levi Garraway, Roche’s Chief Medical Officer, expressed disappointment in the results, stating, “it was our hope that this combination might yield improved outcomes” in metastatic non-squamous NSCLC. The company will work with investigators to terminate the study and plans to present the complete findings and analyses at an upcoming medical congress.

Tiragolumab is an investigational antibody targeting TIGIT, an immune receptor on certain cells that cancer exploits to diminish the body’s anti-cancer response. By targeting TIGIT, tiragolumab aims to amplify the immune response, complementing the action of PD-L1 blockers like Tecentriq.

Roche is also investigating tiragolumab in other cancers, including small cell lung cancer, cervical cancer, esophageal cancer, head and neck cancer, and various hematologic and solid tumors. In January 2024, Roche reported that a combination of tiragolumab, Tecentriq, and chemotherapy led to a significant improvement in PFS for patients with esophageal squamous cell carcinoma compared to chemotherapy alone. The combination also showed improved overall survival.

In light of the SKYSCRAPER-06 results, Roche will review and potentially adjust its other clinical development programs involving tiragolumab.

In a separate development, Roche received FDA approval in April 2024 for Alecensa (alectinib) as an adjuvant treatment for early-stage NSCLC positive for ALK mutations, making it the first ALK inhibitor approved for this indication.