Alpine bails on phase 1 cancer asset after 2nd patient death reported in Keytruda combo study

After a second patient death, Alpine Immune Sciences is terminating enrollment for two trials assessing its cancer asset davoceticept, including the biotech’s combo study with Merck’s Keytruda for adults with advanced malignancies.

Both patients who died were participants in NEON-2, Alpine’s phase 1 dose-escalation and combo study of davoceticept, a conditional costimulator of CD28. The most recent patient death was attributed to cardiogenic shock, according to a company release, a condition in which the heart is unable to pump enough blood and oxygen to vital organs. The participant, who had metastatic colorectal cancer previously treated with colectomy and several prior chemotherapies, had received a single dose each of davoceticept and Keytruda.

The death follows a partial clinical hold slapped on the trial back in March after the first patient death was reported. The individual had also received a single dose each of davoceticept and Keytruda and died from cardiogenic shock.

Now, Alpine is cutting short its two studies involving the investigational CD28 costimulator and dual checkpoint inhibitor, including NEON-1, a phase 1 study evaluating davoceticept as a monotherapy.

“We have determined it is in the best interest of all patients to terminate enrollment in the davoceticept studies and we will continue to work with the FDA, Merck, the study safety monitoring committee and the study investigators to further understand this important safety issue,” Alpine CEO Mitchell Gold, M.D., said in an Oct. 24 release. “Davoceticept has shown encouraging signs of clinical activity and it is unfortunate we have not yet been able to identify a safe dose regimen for the combination with pembrolizumab.”

The Seattle biotech said it is conducting a comprehensive assessment of all participants in both NEON trials. 

In the meantime, Alpine will refocus resources toward ALPN-303, its investigational dual BAFF/APRIL B cell cytokine inhibitor designed to treat multiple autoantibody-related inflammatory diseases. The biotech will also continue advancing its AbbVie-partnered acazicolcept, or ALPN-101, for systemic lupus erythematosus.