A Phase I/II Open-Label Study of Molibresib for the Treatment of Relapsed/Refractory Hematologic Malignancies

Dawson, MA; Borthakur, G; Huntly, BJP; Karadimitris, A; Alegre, A; Chaidos, A; Vogl, DT; Pollyea, DA; Davies, FE; Morgan, GJ; Glass, JL; Kamdar, M; Mateos, MV; Tovar, N; Yeh, P; Delgado, RG; Basheer, F; Marando, L; Gallipoli, P; Wyce, A; Krishnatry, AS; Barbash, O; Bakirtzi, E; Ferron-Brady, G; Karpinich, NO; McCabe, MT; Foley, SW; Horner, T; Dhar, A; Kremer, BE; Dickinson, M

Author(s): Dawson, MA; Borthakur, G; Huntly, BJP; Karadimitris, A; Alegre, A; Chaidos, A; Vogl, DT; Pollyea, DA; Davies, FE; Morgan, GJ; Glass, JL; Kamdar, M; Mateos, MV; Tovar, N; Yeh, P; Delgado, RG; Basheer, F; Marando, L; Gallipoli, P; Wyce, A; Krishnatry, AS; Barbash, O; Bakirtzi, E; Ferron-Brady, G; Karpinich, NO; McCabe, MT; Foley, SW; Horner, T; Dhar, A; Kremer, BE; Dickinson, M;
Details: Publication Year 2023,Volume 29,Issue #4,Page 711-722
Journal Title: Clinical Cancer Research
Publication Type: Research article
Abstract: PURPOSE: Molibresib is a selective, small molecule inhibitor of the bromodomain and extra-terminal (BET) protein family. This was an open-label, two-part, Phase I/II study investigating molibresib monotherapy for the treatment of hematological malignancies (NCT01943851). PATIENTS AND METHODS: Part 1 (dose escalation) determined the recommended Phase 2 dose (RP2D) of molibresib in patients with acute myeloid leukemia (AML), Non-Hodgkin lymphoma (NHL), or multiple myeloma. Part 2 (dose expansion) investigated the safety and efficacy of molibresib at the RP2D in patients with relapsed/refractory myelodysplastic syndrome (MDS; as well as AML evolved from antecedent MDS) or cutaneous T-cell lymphoma (CTCL). The primary endpoint in Part 1 was safety and the primary endpoint in Part 2 was objective response rate (ORR). RESULTS: There were 111 patients enrolled (87 in Part 1, 24 in Part 2). Molibresib RP2Ds of 75 mg daily (for MDS) and 60 mg daily (for CTCL) were selected. Most common Grade 3+ adverse events included thrombocytopenia (37%), anemia (15%), and febrile neutropenia (15%). Six patients achieved complete responses [3 in Part 1 (2 AML, 1 NHL), 3 in Part 2 (MDS)], and 7 patients achieved partial responses [6 in Part 1 (4 AML, 2 NHL), 1 in Part 2 (MDS)]. The ORRs for Part 1, Part 2, and the total study population were 10% [95% confidence interval (CI), 4.8-18.7], 25% (95% CI, 7.3-52.4), and 13% (95% CI, 6.9-20.6), respectively. CONCLUSIONS: While antitumor activity was observed with molibresib, use was limited by gastrointestinal and thrombocytopenia toxicities. Investigations of molibresib as part of combination regimens may be warranted.
Publisher: American Association for Cancer Research
Keywords: Humans; *Lymphoma, Non-Hodgkin/drug therapy; *Hematologic Neoplasms/drug therapy; *Leukemia, Myeloid, Acute/drug therapy; *Thrombocytopenia
Department(s): Clinical Haematology
PubMed ID: 36350312
Publisher's Version: https://doi.org/10.1158/1078-0432.CCR-22-1284
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.CCR-22-1284
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-04-06 06:53:43

Last Modified: 2023-04-17 11:52:08