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March 20, 2023
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A Phase I/II Open-Label Study of Molibresib for the Treatment of Relapsed/Refractory Hematologic Malignancies

Publicated to: Clinical Cancer Research. 29 (4): 711-722 - 2023-02-15 29(4), DOI: 10.1158/1078-0432.ccr-22-1284

Authors:

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

Addenbrookes Hosp, Cambridge, England - Author
GSK, Collegeville, PA USA - Author
Hosp Univ La Princesa & Quironsalud, Madrid, Spain - Author
Hosp Univ Salamanca, IBSAL, CIBERONC, Salamanca, Spain - Author
Hosp Virgen Victoria, Malaga, Spain - Author
Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, London, England - Author
Imperial Coll London, Hugh & Josseline Langmuir Ctr Myeloma Res, Ctr Haematol, Dept Immunol & Inflammat, London, England - Author
Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY USA - Author
NYU, Perlmutter Canc Ctr, Langone Med Ctr, New York, NY USA - Author
Royal Melbourne Hosp, Peter MacCallum Canc Ctr, Dept Clin Haematol, Melbourne, Vic, Australia - Author
Univ Barcelona, Hosp Clin, Barcelona, Spain - Author
Univ Cambridge, Cambridge, England - Author
Univ Colorado, Sch Med, Aurora, CO USA - Author
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia - Author
Univ Penn, Abramson Canc Ctr, Philadelphia, PA USA - Author
Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX USA - Author
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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) investi-gated 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 thorn 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, 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 moli-bresib, use was limited by gastrointestinal and thrombocytopenia toxicities. Investigations of molibresib as part of combination regi-mens may be warranted.
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Keywords

Brd4Bromodomain inhibitorsExpressionInternational working groupProteinsRecognitionResponse criteria

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Clinical Cancer Research due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 26/322, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-01-01:

  • WoS: 21
  • Scopus: 25
  • Europe PMC: 21
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-01-01:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 20.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 21 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 18.
  • The number of mentions on the social network X (formerly Twitter): 27 (Altmetric).
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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Australia; United Kingdom; United States of America.

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Awards linked to the item

The funder (GSK) provided support in the form of salaries for authors and provided general feedback on study design. The authors were solely responsible for data collection and analysis and preparation of the article. It is current GSK policy that all clinical studies be published. The specific roles of these authors are articulated in the "author contributions " section (116183; NCT01943851) .Editorial support was provided by Anna Polyakova, PhD, at Fishawack Indicia Ltd. of Fishawack Health, UK, and Moamen Hammad of Scion, London, UK, and was funded by GSK.
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