Axatilimab may present a new therapeutic strategy in chronic GvHD

Axatilimab showed promising efficacy outcomes and a favourable safety profile in participants with chronic graft-versus-host disease (GvHD). Swift and durable responses were observed across subgroups.

The investigational monoclonal antibody axatilimab inhibits the colony-stimulating factor-1 receptor (CSF-1R) on monocytes and macrophages. The current phase 2 AGAVE-201 trial (NCT04710576) included 241 participants who were randomised 1:1:1 to 0.3 mg/kg axatilimab every 2 weeks, 1.0 mg/kg, every 2 weeks, or 3.0 mg/kg every 4 weeks. Participants were at least 2 years of age and had received at least 2 prior lines of systemic therapy. The primary outcome was the overall response rate (ORR) in the first 6 cycles [1].

“The ORR was the highest in the lowest dose group, amounting to 74% in the 0.3 mg/kg group,” explained Prof. Daniel Wolff (University Hospital Regensburg, Germany), who presented the results. The corresponding ORRs in the 1.0 mg/kg and 3.0 mg/kg arms were 67% and 50%, respectively. In the lowest dose group, the median time-to-response was 1.7 months and 60% of the responses were maintained for at least 12 months. Focussing on the results from the 0.3 mg/kg arm for the rest of his talk, Prof. Wolff continued: “High response rates (>75%) were seen in participants who had received prior FDA-approved therapies.” Responses in fibrosis-dominated organs were remarkable, with response rates of 78% in the oesophagus, 76% in joints and fascia, 47% in lung tissue, and 27% in skin tissue. The median failure-free survival in the lowest dose group was 17.3 months.

In the lowest dose group, only 6.3% of the participants discontinued axatilimab due to adverse events. Periorbital oedema was documented in 2.5% of the participants, and fatigue and headache occurred in 22.8% and 19.0% of the participants, respectively. Finally, 17.7% of the participants experienced at least 1 adverse event of grade 3 or higher.

In conclusion, axatilimab, at a dose of 0.3 mg/kg, administered every 2 weeks delivered promising efficacy data with a manageable safety profile in participants with chronic GvHD. “The unique mechanism of action of axatilimab may represent a novel therapeutic branch in this patient population,” concluded Prof. Wolff.

1. Wolff D, et al. Safety and efficacy of axatilimab at 3 different doses in patients with chronic graft-versus-host disease (AGAVE-201). Abstract 1, 65^th ASH Annual Meeting, 9–12 December 2023, San Diego, CA, USA.

 

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Posted on 7 February, 20247 February, 2024