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Background Severe checkpoint inhibitor-associated pneumonitis (CIP) represents a potentially fatal immune-related adverse event (irAE) with limited evidence from clinical trials that guides therapeutic interventions. This multicenter, randomized controlled trial aims to evaluates the efficacy/safety of ruxolitinib—a non-selective Janus-associated kinase (JAK) inhibitor—as adjunctive therapy to corticosteroids in patients with severe CIP.Methods This investigator-initiated, open-label, phase 2 trial enrolled patients with severe (CTCAE grade 3-4) CIP. With a predefined sample size of 60 participants, participants were randomized 1:1 to receive glucocorticoids alone (control arm) or glucocorticoids plus ruxolitinib (ruxolinitib arm). All patients initiated predinisone no less than 1 mg/kg/day with subsequent taper. The ruxolitinib arm additionally received ruxolitinib 5 mg twice daily for 2 weeks, followed by 5 mg daily for 2 weeks. The primary endpoint was the proportion achieving CTCAE grade 1 CIP resolution by week 8 while maintaining ≤10 mg/day prednisone equivalents. Continuous variables were analyzed using a mixed-effects model for repeated measures with treatment group, study visit and treatment-by-visit interaction.Results Between April 2023 and May 2025, 49 patients were enrolled. Among the first 39 completing 8-week follow-up (control arm: n=18; ruxolitinib arm: n=21), 7 control patients versus 15 ruxolitinib-treated patients achieved the primary endpoint (nominal *p*=0.057). Figure 1 illustrates longitudinal CTCAE grade changes in evaluable patients with ≥1 follow-up assessment. Figure 2 demonstrates earlier CIP resolution trends in the ruxolitinib arm among patients with known serial grade documentation. The mixed-effects model identified significant effects for: (a) the main effect of study visit; (b) treatment-by-visit interaction (*p*<0.01). Mortality occurred in 1 ruxolitinib-treated patient (refractory pneumothorax) and 2 control patients (1 CIP exacerbation, 1 disease progression).Conclusions This phase 2 analysis suggests a potential clinical benefit of ruxolitinib over glucocorticoid monotherapy in severe checkpoint inhibitor-associated pneumonitis, evidenced by earlier response trends and higher resolution rates without serious safety signals. These preliminary data support further evaluation of ruxolitinib as an adjunctive therapy for severe CIP. ClinicalTrials.gov Identifier: NCT05899725 Abstract 1060 Figure 1Proportion of patients with varied CIP Grade during follow-up in both arms. Evaluable patients with ≥1 follow-up assessment (control arm: n=23, ruxolitinib arm: n=24)Abstract 1060 Figure 2Proportion of patients with resolution from severe CIP Grade during follow-up in both arms. Patients with known serial grade documentation. Severe CIP = CIP CTCAE grade 3-5, resolution from severe CIP=CIP CTCAE grade 0-2