Roche has reported promising Phase III results for its investigational cancer drug divarasib, which cut the risk of death by 44% compared with currently available KRAS G12C inhibitors in people with previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC).

 

The results from the Krascendo 1 study showed that patients receiving divarasib lived longer than those treated with the existing drugs sotorasib or adagrasib. Median overall survival with divarasib was approximately 18 months, compared with 12 months in the control group.

 

The findings mark a significant advance in the treatment of a lung cancer subtype for which more effective therapies remain urgently needed.

 

Divarasib also reduced the risk of disease progression or death by 42%, while its objective response rate was nearly double that of sotorasib or adagrasib. The survival and progression-free survival benefits were consistent across clinically relevant patient subgroups, regardless of PD-L1 expression or KEAP1 mutation status.

 

No new safety signals were identified. The most common treatment-related adverse events were predominantly low-grade and manageable, according to Roche.

 

“The phase III Krascendo 1 results demonstrate the potential for divarasib to become a new standard of care for people with previously treated KRAS G12C-mutated lung cancer,” said Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development. 

 

"The superior efficacy against the current standard of care demonstrated in this head-to-head trial reinforces divarasib's best-in-class profile. We are working closely with health authorities to bring this new treatment option to the people who need it.”

 

The KRAS G12C mutation is among the most common KRAS mutations, occurring in approximately one in eight people with NSCLC. Evidence suggests that patients with this mutation may have poorer outcomes than those whose cancer carries an unmutated KRAS gene.

 

Although first-generation KRAS G12C-targeted drugs have been approved, treatment options remain limited, particularly for patients whose disease returns or progresses after initial therapy.

 

“New life-extending treatments are greatly needed, as most patients with this type of cancer will eventually relapse after initial therapy, and there are limited effective treatments for recurrent disease,” said study lead author Ferdinandos Skoulidis, Professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. 

 

“The Krascendo 1 results highlight divarasib’s practice-changing potential, as the first KRAS inhibitor to meaningfully improve overall survival for people with previously treated KRAS G12C-mutated lung cancer, compared with current treatment options.”

 

Krascendo 1 is the only global head-to-head study to evaluate a next-generation KRAS G12C inhibitor against approved first-generation inhibitors, Roche said.

 

The trial met its primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful improvements in both overall survival and progression-free survival for divarasib compared with sotorasib or adagrasib.