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

Mark A. Dawson, Gautam Borthakur, Brian J.P. Huntly, Anastasios Karadimitris, Adrian Alegre, Aristeidis Chaidos, Dan T. Vogl, Daniel A. Pollyea, Faith E. Davies, Gareth J. Morgan, Jacob L. Glass, Manali Kamdar, Maria Victoria Mateos, Natalia Tovar, Paul Yeh, Regina García Delgado, Faisal Basheer, Ludovica Marando, Paolo Gallipoli, Anastasia WyceAnu Shilpa Krishnatry, Olena Barbash, Evi Bakirtzi, Geraldine Ferron-Brady, Natalie O. Karpinich, Michael T. McCabe, Shawn W. Foley, Thierry Horner, Arindam Dhar, Brandon E. Kremer, Michael Dickinson

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7 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)711-722
Number of pages12
JournalClinical Cancer Research
Issue number4
Publication statusPublished - 1 Feb 2023
Externally publishedYes

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