2026-04-17T17:18:02Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/92522024-06-06T08:39:38Zcom_2072_378070com_2072_378040col_2072_378092

BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas Vieito Villar, Maria Sepúlveda, Juan Manuel Galvao De Aquiar, Vladimir Hernández-Guerrero, T. Doger, B. Saavedra Gadea, Omar Carpio Segura, Cecilia Carmen Braña Garcia, Irene Moreno, Victor Institut Català de la Salut [Moreno V, Hernández-Guerrero T, Doger B] START Madrid-FJD, Hospital Universitario Fundación Jimenez Diaz, Madrid, Spain. [Vieito M, Galvao V, Saavedra O, Carpio C, Braña I] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Sepulveda JM] Hospital Universitario 12 de Octubre, Madrid, Spain Vall d'Hebron Barcelona Hospital Campus Cèl·lules B - Tumors - Tractament Medicaments antineoplàstics - Ús terapèutic DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents Other subheadings::Other subheadings::/therapeutic use ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos Otros calificadores::Otros calificadores::/uso terapéutico B-cell lymphoma; Cancer therapy; CNS cancer Limfoma de cèl·lules B; Teràpia del càncer; Càncer del SNC Linfoma de células B; Terapia del cáncer; Cáncer del SNC Bromodomain and extraterminal proteins (BET) play key roles in regulation of gene expression, and may play a role in cancer-cell proliferation, survival, and oncogenic progression. CC-90010-ST-001 (NCT03220347) is an open-label phase I study of trotabresib, an oral BET inhibitor, in heavily pretreated patients with advanced solid tumors and relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Primary endpoints were the safety, tolerability, maximum tolerated dose, and RP2D of trotabresib. Secondary endpoints were clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD] of ≥4 months’ duration), objective response rate (CR + PR), duration of response or SD, progression-free survival, overall survival, and the pharmacokinetics (PK) of trotabresib. In addition, part C assessed the effects of food on the PK of trotabresib as a secondary endpoint. The dose escalation (part A) showed that trotabresib was well tolerated, had single-agent activity, and determined the recommended phase 2 dose (RP2D) and schedule for the expansion study. Here, we report long-term follow-up results from part A (N = 69) and data from patients treated with the RP2D of 45 mg/day 4 days on/24 days off or an alternate RP2D of 30 mg/day 3 days on/11 days off in the dose-expansion cohorts (parts B [N = 25] and C [N = 41]). Treatment-related adverse events (TRAEs) are reported in almost all patients. The most common severe TRAEs are hematological. Toxicities are generally manageable, allowing some patients to remain on treatment for ≥2 years, with two patients receiving ≥3 years of treatment. Trotabresib monotherapy shows antitumor activity, with an ORR of 13.0% (95% CI, 2.8–33.6) in patients with R/R DLBCL (part B) and an ORR of 0.0% (95% CI, 0.0–8.6) and a CBR of 31.7% (95% CI, 18.1–48.1) in patients with advanced solid tumors (part C). These results support further investigation of trotabresib in combination with other anticancer agents. This study was sponsored by Celgene, a Bristol Myers Squibb Company. The study sponsor was involved in the study design, analysis of data, and writing the manuscript. Medical writing and editorial assistance were provided by Bernard Kerr, PGDipSci, and Agata Shodeke, of Spark, funded by Bristol Myers Squibb. 2023-03-27T11:46:34Z 2023-03-27T11:46:34Z 2023-03-13 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Moreno V, Vieito M, Sepulveda JM, Galvao V, Hernández-Guerrero T, Doger B, et al. BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas. Nat Commun. 2023 Mar 13;14:1359. 2041-1723 https://hdl.handle.net/11351/9252 10.1038/s41467-023-36976-1 36914652 eng Nature Communications;14 https://doi.org/10.1038/s41467-023-36976-1 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf application/pdf Nature Portfolio Scientia