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| IUPAC name 2-oxazolobenzazepin-4-yl]acetamide | |
| Other names CPI-0610 | |
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| ATC code | L01XX84 (WHO) |
| Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references | |
Pelabresib (CPI-0610; PELA) is an investigational oral small-molecule drug designed to inhibit bromodomain and extra-terminal domain (BET)-mediated gene transcription involved in myelofibrosis pathogenesis.
Description
A phase one study of pelabresib in patients with relapsed/refractory lymphomas found pelabresib is capable of BET target gene suppression in an exposure-dependent manner with an acceptable safety profile leading to the recommended phase II dose of the 125 mg tablet once daily.
In MANIFEST-2, a phase three, randomized, blinded study compares pelabresib and ruxolitinib with placebo and ruxolitinib in myelofibrosis patients that have not been previously treated with Janus kinase inhibitors (JAKi).
NCT02158858, a phase one/two open-label, sequential dose escalation study of pelabresib in patients with previously treated acute leukemia, myelodysplastic syndrome, myelodysplastic/myeloproliferative neoplasms, and myelofibrosis is ongoing.
A third study, NCT06401356, is ongoing to provide continued access to treatment with pelabresib for patients who previously received pelabresib in a parent study and to continue collecting safety and efficacy information, such as a patient's leukemia-free survival and overall survival status during and after the treatment is ended.
References
- Rampal, Raajit; Grosicki, Sebastian; Chraniuk, Dominik; Abruzzese, Elisabetta; Bose, Prithviraj; Gerds, Aaron Thomas; Vannucchi, Alessandro M.; Palandri, Francesca; Lee, Sung-Eun; Gupta, Vikas; Lucchesi, Alessandro; Kuykendall, Andrew Tucker; Mesa, Ruben A.; Kiladjian, Jean-Jacques; Talpaz, Moshe (2024-05-29). "Updated safety and efficacy data from the phase 3 MANIFEST-2 study of pelabresib in combination with ruxolitinib for JAK inhibitor treatment-naïve patients with myelofibrosis". Journal of Clinical Oncology. 42 (16_suppl): 6502. doi:10.1200/JCO.2024.42.16_suppl.6502. ISSN 0732-183X.
- Mascarenhas, John; Kremyanskaya, Marina; Patriarca, Andrea; Gupta, Vikas; Palandri, Francesca; Devos, Timothy; Rampal, Raajit K; Talpaz, Moshe; Vannucchi, Alessandro; Kuykendall, Andrew; Kiladjian, Jean-Jacques; Verstovsek, Srdan; Mesa, Ruben; Colak, Gozde; Li, Qing (2022-11-15). "Pelabresib (CPI-0610) Combined with Ruxolitinib for JAK Inhibitor Treatment-Naïve Patients with Myelofibrosis: Durability of Response and Safety Beyond Week 24". Blood. 140 (Supplement 1): 586–589. doi:10.1182/blood-2022-158147. ISSN 0006-4971. Archived from the original on 2024-06-10. Retrieved 2024-11-29.
- Constellation Pharmaceuticals (2024-05-07). A Phase 1 Study of CPI-0610, a Small Molecule Inhibitor of BET (Bromodomain and Extra-terminal) Proteins, in Patients With Progressive Lymphoma (Report). clinicaltrials.gov. Archived from the original on 2024-06-04. Retrieved 2024-11-29.
- Verstovsek, Srdan; Salama, Mohamed E; Mascarenhas, John; Talpaz, Moshe; Mesa, Ruben A.; Vannucchi, Alessandro; Rampal, Raajit; Oh, Stephen T.; Olteanu, Horatiu; Chiu, April; Chen, Dong; Hanson, Curtis A.; Curto-Garcia, Natalia; Taverna, Pietro; Cui, Jike (2021-11-23). "Disease-Modifying Potential of BET Inhibitor Pelabresib (CPI-0610) As Demonstrated By Improvements in Bone Marrow Function and Clinical Activity in Patients with Myelofibrosis - Preliminary Data". Blood. 138: 2568. doi:10.1182/blood-2021-152267. ISSN 0006-4971.
- Constellation Pharmaceuticals (2024-10-25). A Phase 3, Randomized, Double-blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAKi Treatment Naive MF Patients (Report). clinicaltrials.gov. Archived from the original on 2024-10-05. Retrieved 2024-11-29.
- Ferreira Gomes, Guadalupe; Harrison, Claire (2023-08-17). "Pelabresib (CPI-0610): An Exciting Novel Drug for the Treatment of Myelofibrosis". Current Hematologic Malignancy Reports. 18 (4): 113–120. doi:10.1007/s11899-023-00696-6. ISSN 1558-822X. PMID 37195585.
- Constellation Pharmaceuticals (2024-10-31). A Phase 1/2 Study of CPI-0610, a Small Molecule Inhibitor of BET Proteins: Phase 1 (Dose Escalation of CPI-0610 in Patients With Hematological Malignancies) and Phase 2 (Dose Expansion of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis and Essential Thrombocytopenia) (Report). clinicaltrials.gov.
- Constellation Pharmaceuticals (2024-10-28). An Open-Label, Multicenter, Extension Study for Patients Previously Enrolled in Studies with Pelabresib (Report). clinicaltrials.gov.