Exelixis Shares Dive After Announcing News of Carcinoma Survival Data
A planned primary analysis of the ongoing Phase III COSMIC-312 trial found cabozantinib (CABOMETYX®) plus atezolizumab significantly improved progression-free survival (PFS) compared with sorafenib in patients with previously untreated advanced hepatocellular carcinoma (HCC). However, an improvement in overall survival (OS) had not reached statistical significance at the time of the analysis. The two companies studying the regimen for HCC, Exelixis and Ipsen, suggest the probability of reaching significance at the final analysis is low.
Given the news of the OS trial endpoint, shares in Exelixis were down 13% premarket on Monday.
According to Exelixis and Ipsen, the preliminary OS data suggest the final analysis will not likely show a statistically significant improvement in OS with the combination regimen at the final analysis, despite a trend favoring cabozantinib plus atezolizumab. Even though the companies anticipate this lack of difference between the comparator arms, the study will continue to the planned final analysis for OS, with results expected by early next year.
In the PFS intent-to-treat population of the Phase III COSMIC-312 trial, the use of cabozantinib and atezolizumab was associated with a significant reduction in the risk of disease progression or death by approximately 37% compared with sorafenib monotherapy (hazard ratio, 0.63; 99% CI: 0.44-0.91; p=0.0012).
Additionally, the safety of the combination regimen was consistent with each individual medicine’s known safety profiles. Likewise, the investigators identified no new safety signals. Exelixis said it plans to discuss the findings from the trial and next steps for regulatory filing with the U.S. Food and Drug Administration (FDA).
“While we are encouraged by the data supporting the potential for the combination of cabozantinib and atezolizumab to reduce the risk of disease progression or death, we are disappointed by the interim result of lack of significant improvement on overall survival versus the comparator arm,” according to a statement made by Exelixis’ President and Chief Executive Officer, Michael M. Morrissey, Ph.D.
Dr. Morrissey added that the company is continuing to evaluate the data as they mature to further “understand the potential impact of various contributing factors on the results, including patient demographics, subsequent anti-cancer therapy and the impact of COVID-19 on the trial.” He added that the company will present additional results at an upcoming medical meeting.
Exelixis and its partner Ipsen have been working on CABOMETYX for some time. Back in March, received European Commission Approval for CABOMETYX® (cabozantinib) combined with OPDIVO® (nivolumab) as an initial therapy for patients with advanced renal cell carcinoma. The European Commission approved the therapeutic combination based on data from the Phase III CheckMate-9ER trial. In this study, the therapies improved OS compared with sunitinib monotherapy.
In 2018, the two companies received a positive Committee for Medicinal Products for Human Use opinion for CABOMETYX monotherapy as an HCC treatment in adults previously treated with sorafenib. During that time, the two companies disclosed the terms of their collaboration agreement, which saw Exelixis eligible for a milestone payment totaling $40 million for ultimate approval of the therapy in the second-line treatment setting for HCC.