Chronic Graft-Versus-Host Disease (cGVHD) affects 30 to 50% of patients who have received allogeneic hematopoietic cell transplantation (HCT). Many patients with cGVHD fail to respond to available therapies or eventually progress. Sclerosis and lung involvement are often difficult to treat and may lead to poor outcomes.

Blocking CSF-1 / CSF-1R signaling may prevent and treat cGVHD

Axatilimab is an anti-CSF-1R monoclonal antibody targeting macrophage-driven diseases

High-affinity humanized IgG4 monoclonal antibody

Blocks the binding of both CSF-1 & IL-34 ligands

Administered via 30-minute infusion every 2 to 4 weeks

Highly effective in selectively reducing levels of circulating pro-fibrotic/non-classical monocytes

Intermittent dosing allows for monocyte recovery prior to subsequent dose

Phase 1/2 trial enrolled 40 patients; phase 1 dose escalation and phase 2 dose expansion

Study population included patients who were 6 years of age or older with active cGVHD after 2 or more prior treatments and a KPS of 60 or higher

1 patient each in Cohort 1 and 2 (0.15 mg/kg Q2W and 0.5 mg/kg Q2W, respectively)

Primary endpoints: Safety, overall response rate (ORR), recommended phase 2 dose (RP2D)

Primary endpoint: ORR (2014 NIH consensus criteria)

Median age: 59 (16-73); majority were male

65% received myeloablative transplant; 93% received a peripheral blood transplant

65% of patients had at least 4 organs involved

Majority had received at least one of the new FDA-approved therapies

Treatment was well-tolerated with very few discontinuations due to adverse events (AEs)

Most common AEs were increases in AST/ALT, CPK, amylase, and lipase without evidence of end organ damage; periorbital edema

Infection rates were in line with contemporary experience in cGVHD

Best change in normalized Lee Symptom Score (LSS)

Median change (points): -7.8 (range 3.1, -37.6)

16 (53%) of 30 LSS-evaluable patients achieved a 7-point reduction from baseline

Improvement seen regardless of response by NIH consensus criteria

Responses seen in all dose levels and across all organ systems

Axatilimab advances to Pivotal Phase 2 Trial – AGAVE-201

Inclusion: 2 years and older, recurrent or refractory active cGVHD after 2 or more lines of systemic therapy

Stratification factors: Prior therapy (ibrutinib, ruxolitinib, belumosudil)

1:1:1 randomization to 0.3 mg/kg Q2W (N = 70); 1 mg/kg Q2W (N = 70); 3 mg/kg Q4W (N = 70)

Videos

Dr Carrie Lynn Kitko discusses updated results from a phase 1/2 study evaluating the safety, tolerability, and efficacy of axatilimab in pts ≥ 6 years of age with active cGVHD despite ≥ 2 prior lines of systemic therapy.

Rapid Readouts: Safety, Tolerability, and Efficacy of Axatilimab, a CSF-1R humanized antibody, for Chronic Graft-versus-Host Disease after 2 or more Lines of Systemic Treatment

Carrie Lynn Kitko, MD

Articles

Rapid Readouts: Safety, Tolerability, and Efficacy of Axatilimab, a CSF-1R humanized antibody, for Chronic Graft-versus-Host Disease after 2 or more Lines of Systemic Treatment