Axatilimab represents ‘highly effective’ therapeutic strategy for chronic GVHD
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Key takeaways:
- The study met its primary efficacy endpoint for overall response rate at all three dose levels.
- Median duration of response had not been reached for any dose level.
SAN DIEGO — Axatilimab conferred clinically meaningful and durable responses at three dose levels among individuals with chronic graft-versus-host disease, randomized study results showed.
Data from the phase 2 AGAVE-201 trial suggest superior efficacy and safety using the lowest dose evaluated, according to findings presented during the plenary scientific session at ASH Annual Meeting and Exposition.
“Axatilimab at 0.3 mg/kg every two weeks is highly effective and has a manageable safety profile [for] patients with recurrent or refractory chronic GVHD,” Daniel Wolff, MD, senior physician and head of the GvHD Competence Center at Regensburg University Hospital in Germany, said during a presentation. “Axatilimab’s unique mechanism of action may represent a new therapeutic strategy in chronic GVHD.”
Background
Chronic GVHD is a difficult-to-treat fibrotic disease that affects 30% to 50% of patients who undergo allogeneic hematopoietic stem cell transplant, according to Wolff.
“Despite recent approval of therapies to treat this condition, there remains an unmet need to develop more effective agents ... that can improve quality of life,” Wolff said.
Methods
The multicenter AGAVE-201 trial evaluated axatilimab (SNDX-6352; Incyte/Syndax Pharmaceuticals) — an investigational monoclonal antibody that targets the colony stimulating factor-1 receptor — for adults and children with chronic GVHD who received at least two previous lines of therapy.
The pivotal study examined three doses for patients with relapsed or refractory chronic GVHD who underwent previous allogenic hematopoietic stem cell transplant.
Researchers randomly assigned 241 study participants in a 1:1:1 ratio to IV axatilimab at doses of 0.3 mg/kg every 2 weeks, 1 mg/kg every 2 weeks or 3 mg/kg every 4 weeks.
Overall response rate during the first six cycles (24 weeks) of treatment served as the primary efficacy endpoint. Secondary endpoints included safety and the proportion of study participants who reported a statistically significant reduction of symptoms using the modified Lee Symptom Scale score.
Key findings
The study met its primary endpoint for all three doses, as more than half of patients in each group responded to therapy.
Researchers reported an ORR of 74% (95% CI, 63-83) among those assigned 0.3 mg/kg every 2 weeks, 67% (95% CI, 55-77) among those assigned 1 mg/kg every 2 weeks, and 50% (95% CI, 39-61) among those assigned 3 mg/kg every 4 weeks.
Median duration of response had not been reached for any dose group. As of the data cutoff date April 7, investigators reported ongoing responses to therapy for 60% of patients assigned 0.3 mg/kg every 2 weeks or 1 mg/kg every 2 weeks, with 55% of those assigned 3 mg/kg every 4 weeks having ongoing responses.
Clinical benefits measured by significant changes in symptom scores occurred among 55% in the 0.3 mg/kg every 2 weeks cohort, 54% in the 1 mg/kg every 2 weeks cohort, and 36% in the 3 mg/kg every 4 weeks cohort.
Adverse events prompted treatment discontinuation for 6% of patients assigned 0.3 mg/kg every 2 weeks, 22% of those assigned 1 mg/kg every 2 weeks, and 18% of those assigned 3 mg/kg every 4 weeks. Fatal adverse events occurred among 1.3% of patients assigned 0.3 mg/kg every 2 weeks, 8.6% of those assigned 1 mg/kg every 2 weeks, and 7.6% of those assigned 3 mg/kg every 4 weeks.
Clinical implications
The results in all three groups showed “rapid and durable responses” among a heavily pretreated patient population, including those who experienced further symptoms after receiving approved therapies for chronic GVHD, Wolff said.
“Adverse events were mostly low grade, reversible and increased with higher doses of axatilimab,” he said. “A significant reduction of symptom burden was reported by most patients, including those with fibrotic chronic GVHD manifestations.”
Collapse
Wolff D, et al. Abstract 1. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2023; San Diego.
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