Cabometyx Combo Doesn’t Meet Survival Endpoint in Advanced Liver Cancer Trial

After a phase 3 trial showed that Cabometyx/atezolizumab did not improve overall survival in patients with hepatocellular carcinoma, Exelixis officials have said they won’t be submitting an NDA for untreated patients with advanced liver cancer.

A final analysis of the second primary endpoint of overall survival from the phase 3 COSMIC-312 trial, which evaluated Exelixis’ Cabometyx (cabozantinib) in combination with Tecentriq (atezolizumab) versus Nexavar (sorafenib) in patients with previously untreated advanced hepatocellular carcinoma (HCC). The final analysis showed neither improvement nor detriment in overall survival.

Exelixis officials have said they don’t intend to submit a supplemental new drug application to the FDA.

In the United States, Cabometyx is approved for the treatment of patients with advanced renal cell carcinoma; patients with HCC who have been previously treated with Nexavar; for patients with advanced RCC as a first-line treatment in combination with Opdivo (nivolumab); and for adult and pediatric patients 12 years of age and older with advanced or metastatic thyroid cancer.

In June 2021, Exelixis had released initial data from this trial, which showed the combination improved progression-free survival, reducing the risk of progression or death by 37%. At the time, the endpoint of overall survival was not reached, and company researchers believed the probability for reaching statistical significance was low.

Still as late as November 2021, company executives were still planning on submitting an NDA based on the progression-free survival data.

Hepatocellular carcinoma is the most common type of liver cancer. It most often occurs in people with chronic liver disease. More than 900,000 new cases of liver cancer are diagnosed worldwide each year, and it is a leading cause of cancer death, accounting for more than 800,000 deaths annually, according to the World Health Organization.