Efficacy and safety of axatilimab at 3 different doses in patients with chronic graft-versus-host disease (cGVHD) and related bronchiolitis obliterans syndrome (BOS): results of a pivotal phase 2 study

<bold>Rationale:</bold> Activity of the anti-CSF-1R monoclonal antibody axatilimab in cGVHD-associated BOS was previously shown in a phase 1/2 study (<ext-link>NCT03604692</ext-link>). <bold>Methods:</bold> AGAVE-201, a pivotal phase 2, open-label, randomized, multicenter study of axatilimab in patients with recurrent/refractory cGVHD (<ext-link>NCT04710576</ext-link>) randomized patients 1:1:1 to intravenous axatilimab at 0.3 mg/kg every 2 weeks (Q2W, n=80), 1 mg/kg Q2W (n=81), or 3 mg/kg every 4 weeks (Q4W, n=80). BOS and cGVHD diagnosis and response criteria followed 2014 National Institutes of Health cGVHD Consensus. The primary efficacy endpoint was cGVHD overall response rate (ORR) in the first 6 cycles (24 weeks). Safety endpoints included frequency and severity of treatment-emergent adverse events (TEAEs). <bold>Results:</bold> BOS was present in 108 (45%) patients. The primary ORR endpoint was met in all cohorts, and along with BOS response rate was highest at the 0.3 mg/kg dose (Table). The median time to BOS response was <3 months. TEAEs were dose dependent in frequency and severity, with majority on-target effects of CSF-1R blockade. TEAE-driven discontinuation occurred in 6% of all patients in the 0.3 mg/kg cohort and 16% of all study patients. <bold>Conclusions:</bold> Axatilimab dose of 0.3 mg/kg Q2W showed the best efficacy and safety in cGVHD and BOS. Axatilimab at the 0.3 mg/kg Q2W dose is being investigated in a Phase 2 study in idiopathic pulmonary fibrosis (<ext-link>NCT06132256</ext-link>). <table-wrap><object-id>erj;64/suppl_68/PA4778/T1</object-id><object-id>T1</object-id><object-id>t1</object-id><table><colgroup></colgroup><tbody><tr><td>Characteristic (%)</td><td>0.3 mg/kg Q2W</td><td>1 mg/kg Q2w</td><td>3 mg/kg Q4W</td></tr><tr><td>Baseline BOS</td><td>40</td><td>51</td><td>44</td></tr><tr><td>FEV1≤39%*</td><td>47</td><td>42</td><td>26</td></tr><tr><td>ORR</td><td>74</td><td>67</td><td>50</td></tr><tr><td>BOS response*</td><td>47</td><td>34</td><td>37</td></tr></tbody></table></table-wrap> *Among patients with baseline BOS