LIMBER-304 phase III: Parsaclisib + ruxolitinib for MF

Results from the randomized, double-blind, placebo-controlled, phase III LIMBER-304 study (NCT04551053), evaluating add-on parsaclisib, a phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, + ruxolitinib in 177 adults with myelofibrosis (MF) and suboptimal or declining response to ruxolitinib, were published in The Oncologist by Kiladjian et al. The primary endpoint was the proportion of patients achieving a ≥25% spleen volume reduction (SVR) from baseline to Week 24. The key secondary endpoint was the proportion of patients with a ≥50% reduction in Myelofibrosis Symptom Assessment Form (MFSAF) total symptom score (TSS) from baseline to Week 24. 

Key data: At Week 24, SVR ≥25% was achieved by 16.7% of study participants receiving parsaclisib + ruxolitinib (n = 90) vs 9.7% receiving placebo + ruxolitinib (n = 87). By Week 24, a ≥50% reduction in MFSAF TSS was observed in 17.1% vs 14.1%, respectively. Neither endpoint reached statistical significance. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 60.0% of patients receiving parsaclisib + ruxolitinib vs 42.5% of patients receiving placebo + ruxolitinib. The most frequently reported Grade ≥3 TEAEs in the parsaclisib + ruxolitinib cohort were anemia (22.2%), decreased platelet count (16.7%), thrombocytopenia (10.0%), pneumonia (7.8%), COVID-19 (5.6%), and COVID-19 pneumonia (5.6%). A greater proportion of patients receiving parsaclisib vs placebo experienced serious adverse events (SAEs; 36.7% vs 17.2%). The study was terminated early due to futility. 

Key learning: The addition of parsaclisib to ruxolitinib was unlikely to provide clinically meaningful benefits in patients with MF and suboptimal or declining response to ruxolitinib, with a higher incidence of SAEs.