Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)
Summary
A Phase 3, randomized, blinded study comparing pelabresib (CPI-0610) and ruxolitinib with placebo and ruxolitinib in myelofibrosis (MF) patients that have not been previously treated with Janus kinase inhibitors (JAKi). Pelabresib is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.
Timeline
- Start
- 2021-04-09
- Primary completion
- 2023-08-23
- Completion
- 2027-06-30
Outcome
Met primary endpoint
paper The primary endpoint was met in 65.9% of patients randomized to pelabresib-ruxolitinib (n = 214) versus 35.2% to placebo-ruxolitinib PMID 40065169 ↗
registry Pelabresib + Ruxolitinib (Experimental Arm) vs Placebo + Ruxolitinib (Control Arm); p <0.001; Difference in proportion 30.4 (95% CI 21.6 to 39.3) NCT04603495 ↗
release “Pelabresib in combination with ruxolitinib recently met its primary endpoint of spleen volume reduction in the Phase 3 MANIFEST-2 study in JAK inhibitor-naive MF patients” novartis.com ↗
Publications
- Results Harrison CN, Gupta VK, Gerds AT, Rampal R, Verstovsek S, Talpaz M, Kiladjian JJ, Mesa R, Kuykendall AT, Vannucchi AM, Palandri F, Grosicki S, Devos T, Jourdan E, Wondergem MJ, Al-Ali HK, Buxhofer-Ausch V, Alvarez-Larran A, Patriarca A, Kremyanskaya M, Mead AJ, Akhani S, Sheikine Y, Colak G, Mascarenhas J. Phase III MANIFEST-2: pelabresib + ruxolitinib vs placebo + ruxolitinib in JAK inhibitor treatment-naive myelofibrosis. Future Oncol. 2022 Sep;18(27):2987-2997. doi: 10.2217/fon-2022-0484. Epub 2022 Aug 11.
- Results Rampal RK, Grosicki S, Chraniuk D, Abruzzese E, Bose P, Gerds AT, Vannucchi AM, Palandri F, Lee SE, Gupta V, Lucchesi A, Oh ST, Kuykendall AT, Patriarca A, Alvarez-Larran A, Mesa R, Kiladjian JJ, Talpaz M, Scandura JM, Lavie D, Harris M, Kays SK, Li Q, Boxhammer R, Brown B, Jegg AM, Harrison CN, Mascarenhas J. Pelabresib plus ruxolitinib for JAK inhibitor-naive myelofibrosis: a randomized phase 3 trial. Nat Med. 2025 May;31(5):1531-1538. doi: 10.1038/s41591-025-03572-3. Epub 2025 Mar 10.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Pelabresib | Small molecule | 125 mg | — |
| Background | Ruxolitinib | Small molecule | 10 mg | — |
| Background | Ruxolitinib | Small molecule | 15 mg | — |