Axatilimab induces ‘robust responses’ in chronic GVHD
Click Here to Manage Email Alerts
A phase 2 trial of axatilimab for chronic graft-versus-host disease met its primary endpoint, according to the agent’s manufacturer.
At least half of patients treated at each of three dose levels responded to treatment, topline data showed.
Axatilimab (SNDX-6352; Incyte/Syndax Pharmaceuticals) is an investigational monoclonal antibody that targets colony stimulating factor-1 receptor, a cell surface protein thought to control the survival and function of monocytes and macrophages.
The phase 2 AGAVE-201 trial evaluated axatilimab for adults and children with chronic GVHD who received at least two prior lines of therapy.
The study included 241 patients treated at 121 sites in 16 countries.
Study participants received a median four prior systemic therapies. Most (74%) had received ruxolitinib (Jakafi, Incyte), 23% had received belumosudil (Rezurock, Kadmon/Sanofi) and 31% had received ibrutinib (Imbruvica; Janssen, Pharmacyclics).
At baseline, 54% of study participants had at least four organs involved and 45% had lung involvement.
Within 6 months of treatment, researchers reported response rates of 74% (95% CI, 63-83) among those treated at a dose of 0.3 mg/kg every 2 weeks, 67% (95% CI, 55-77) among those treated with a dose of 1 mg/kg every 2 weeks, and 50% (95% CI, 39-61) among those treated at a dose of 3 mg/kg every 4 weeks.
More than half (60%) of those who responded to the 0.3 mg/kg dose maintained their response for at least 1 year. Median duration of response had not been reached.
Researchers reported responses across key patient subgroups, including those previously treated with ruxolitinib, belumosudil or ibrutinib.
Adverse events that occurred among more than 20% of study participants included increased aspartate aminotransferase, blood creatine phosphokinase, lipase, blood lactate dehydrogenase, alanine aminotransferase and fatigue.
More than one-third (42.3%) of study participants experienced serious adverse events, and 15.5% experienced adverse events that led to treatment discontinuation.
In the group treated at the 0.3 mg/kg dose, 38% experienced serious adverse events, with fatigue being the only serious adverse event to occur among more than 20% of patients.
"Chronic GVHD is a very common complication [after] allogeneic hematopoietic stem cell transplant that can have profound effects on patient medical burden and quality of life,” Carrie L. Kitko, MD, medical director of the pediatric stem cell transplant program at Vanderbilt-Ingram Cancer Center, said in a Syndax Pharmaceuticals-issued press release. “More effective treatment options for this significant complication are desperately needed.
“I am highly encouraged by these data, which demonstrate robust responses in a heavily pretreated patient population,” Kitko added. “These findings further support that axatilimab has the potential to provide a clinically meaningful response for patients suffering from this morbid condition."
Complete data will be presented at a medical meeting.
Based on the study results, Incyte and Syndax anticipate submitting a biologics license application to FDA by the end of this year.
The FDA previously granted orphan drug designation to axatilimab for chronic GVHD.
Collapse
Press Release
Click Here to Manage Email Alerts