Alpine Immune Sciences has voluntarily terminated enrollment in two clinical trials of its immuno-oncology asset, davoceticept, after a second patient death.
Seattle-based Alpine Immune Sciences voluntarily terminated enrollment in two clinical trials of its immuno-oncology asset, davoceticept, after a second patient death. The company now plans to focus its attention on ALPN-303 for autoantibody-related inflammatory diseases.
Davoceticept (ALPN-202) was being evaluated in the Phase I NEON-1 trial as a monotherapy and in the Phase I NEON-2 trial in combination with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) in advanced malignancies. NEON-2 was a dose escalation and expansion combination study.
In March, the FDA placed a partial clinical hold on NEON-2 after a patient death. A participant with choroidal melanoma who received a dose of the combination died of cardiogenic shock, a rare condition where the heart can’t pump enough blood and oxygen to the brain and vital organs.
Now a second patient, this one with metastatic colorectal cancer previously treated with colectomy and multiple previous systemic chemotherapies, died, Alpine reported Monday.
The patient was also enrolled in the NEON-2 trial and the cause of death was cardiogenic shock. The company is running a comprehensive evaluation of all NEON trial participants, according to the announcement.
Mitchell H. Gold, M.D., executive chairman and CEO of Alpine, said patient safety remains the company’s highest priority.
“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,” he stated.
Alpine inked the original trial collaboration and supply deal with Merck for NEON 1 and 2 in June 2021.
BioSpace has reached out to Alpine but had not received a response as of press time.
The company will now pivot its resources and energies toward ALPN-303, a potentially best-in-class dual BAFF/APRIL B cell cytokine inhibitor. It is being developed to treat multiple autoantibody-related inflammatory diseases.
The Phase I RUBY-1 trial of ALPN-303 in healthy volunteers as well as preclinical studies showed the drug significantly improved potency against BAFF. It was well tolerated when dosed intravenously or subcutaneously and also showed encouraging preliminary pharmacodynamic data.
Several studies are ongoing or planned, with data expected from the Phase II RUBY trial in systemic lupus erythematosus expecting data in 2026, according to Alpine’s website. Data is expected from the Phase Ib RUBY-3 open-label basket study in the second half of 2023.
ALPN-101 (acazicolcept), a dual CD28/ICOS inhibitor also being developed for lupus erythematosus, will be part of the development program as well. ALPN-101 is partnered with AbbVie.
