MPN-332: Clinical Benefit of Pelabresib (Cpi-0610) in Combination with Ruxolitinib in JAK Inhibitor Treatment-Naïve Myelofibrosis Patients: Interim Efficacy Subgroup Analysis from Arm 3 of the MANIFEST Phase 2 Study

Context: Pelabresib (CPI-0610), a first-in-class, oral, small-molecule inhibitor of BET proteins (BETi), has potential to promote disease-modifying activity through altered gene regulation of key oncogenic, fibrotic, and inflammatory factors in MF. Treatment with JAKi ruxolitinib (rux) or fedratinib in the frontline setting is associated with approximately 30–40% splenic response (spleen volume reduction ≥ 35% [SVR35]) at 6 months. BETi pelabresib monotherapy demonstrated clinical activity in heavily pre-treated MF pts. Therefore, combination of pelabresib with rux is expected to achieve higher SVR35 response rate in JAKi treatment-naive MF pts. Objective: Evaluation of pelabresib in combination with rux in JAKi treatment-naive MF pts. Design: Pts with MF who were not previously treated with JAKi were enrolled in Arm 3 of MANIFEST. The primary endpoint is SVR35 response at wk 24. Pts were treated with pelabresib 125 mg daily on days 1–14 in a 21-day cycle in combination with rux, which was dosed based on the baseline platelet count. Results: As of 29 September 2020, 78 pts were treated, and 66 pts were ongoing. Baseline characteristics were mean age: 67 years; 72% male; primary MF: 54% pts; DIPSS ≥Int-2: 76% pts; IPSS ≥Int-2: 83%; Hgb Conclusions: Pelabresib treatment in combination with rux in JAKi treatment-naive MF pts resulted in spleen volume reduction that was greater than what would be expected with rux alone, regardless of baseline patient disease and demographic characteristics.