Roche Halts TIGIT Trial After Keytruda's Initial Success

Roche's recent clinical trials have brought significant developments in the field of lung cancer treatments, impacting the company's pharmaceutical strategies and stock market performance. Notably, the Swiss drugmaker decided to halt a phase 2/3 lung cancer trial after its TIGIT drug candidate, tiragolumab, was outperformed by Merck & Co.'s Keytruda.

The pivotal data emerged from the SKYSCRAPER-06 study, wherein patients were randomly assigned either the combination of tiragolumab and Roche’s checkpoint inhibitor Tecentriq or Keytruda and chemotherapy. These participants had previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC).

The initial analysis of the survival data revealed that the Keytruda regimen had a superior performance. The progression-free survival (PFS) assessment yielded a hazard ratio of 1.27, indicating that patients in the control group (Keytruda) fared better than those receiving the investigational tiragolumab treatment. A hazard ratio above 1 underscores the control treatment's superior efficacy.

Furthermore, the overall survival (OS) data from SKYSCRAPER-06 did not offer any reprieve for Roche. The OS hazard ratio stood at 1.33, implying that patients on Keytruda had a longer lifespan compared to those administered tiragolumab. This stark contrast in survival outcomes prompted Roche to unblind and stop the study.

Despite the setback, Roche is not abandoning tiragolumab entirely. The company is continuing its investigation of the TIGIT prospect through other clinical trials. However, they acknowledged the need to reassess and potentially revise ongoing tiragolumab programs in light of the SKYSCRAPER-06 findings.

Roche's broader clinical development program for tiragolumab includes several NSCLC studies and trials targeting other lung, esophageal, and liver cancers. The company’s recent track record with tiragolumab reveals mixed results. For instance, SKYSCRAPER-01, another NSCLC trial, previously failed to show improvement in PFS with tiragolumab. However, there were suggestions of a positive impact on OS in leaked data, offering a glimmer of hope for future outcomes.

Roche also faced challenges with other tiragolumab studies. A small cell lung cancer trial reported failure, and the PFS miss in SKYSCRAPER-01 added to the concerns. An esophageal cancer trial did meet its primary endpoint, but the use of an outdated control therapy created uncertainties about the clinical significance of the results.

Looking ahead, if SKYSCRAPER-01 continues to show positive trends, Roche might secure a phase 3 OS win in NSCLC. However, this potential victory could be marred by questions regarding the comparator used in the study. SKYSCRAPER-01 is evaluating the addition of tiragolumab or placebo to Tecentriq, and given the failure to outperform Keytruda in SKYSCRAPER-06, any success in SKYSCRAPER-01 might come with reservations.

The immediate consequence of these clinical trial outcomes was evident in Roche's market performance. Shares in the company opened down by more than 2% in Switzerland, reflecting investor concerns over the recent trial results and their implications for Roche's cancer drug portfolio and future earnings.