Final results from the phase Ia/Ib study of the novel bromodomain and extra-terminal domain inhibitor, BI 894999, in patients with advanced solid tumors or diffuse large B-cell lymphoma Journal Article
| Authors: | Lauer, U. M.; Awada, A.; Postel-Vinay, S.; Shapiro, G. I.; Thieblemont, C.; Piha-Paul, S. A.; Paik, P. K.; Shepard, D. R.; Docampo, L. I.; Galot, R.; Rottey, S.; Sadrolhefazi, B.; Marzin, K.; Musa, H.; Schöffski, P. |
| Article Title: | Final results from the phase Ia/Ib study of the novel bromodomain and extra-terminal domain inhibitor, BI 894999, in patients with advanced solid tumors or diffuse large B-cell lymphoma |
| Abstract: | Background: Bromodomain and extraterminal domain (BET) inhibitors have demonstrated efficacy in solid and hematological malignancies. BI 894999, a novel, orally administered BET inhibitor, has demonstrated preclinical efficacy. Methods: This was an open-label, dose-finding study evaluating BI 894999 for diffuse large B-cell lymphoma (DLBCL; phase Ia extension) and solid tumors [colorectal cancer (CRC), nuclear protein in testis (NUT) carcinoma, metastatic castration-resistant prostate cancer (mCRPC) and small-cell lung cancer (SCLC); phase Ib cohort]. The primary endpoint was dose-limiting toxicities (DLTs) during the maximum tolerated dose (MTD) period (phase Ia) and treatment period (phase Ib). Results: Eighteen patients with DLBCL were enrolled in the phase Ia extension and 79 with solid tumors in phase Ib cohorts (SCLC, n = 12; CRC, n = 14; mCRPC, n = 11; NUT carcinoma, n = 42). Four patients had DLTs in phase Ia and 17 in phase Ib; the most frequent was grade 4 thrombocytopenia. The MTD for DLBCL was 1.5 mg (days 1-14/21). One patient (5.6%) with DLBCL achieved a partial response (PR) and three (16.7%) had stable disease. Of 42 patients with NUT carcinoma, 3 patients (7.1%) had responses (complete response, n = 1; confirmed PR, n = 1; unconfirmed PR, n = 1). Responses in other solid tumor types (n = 37) included one patient (2.7%) with mCRPC who had a confirmed PR. Conclusions: The safety profile of BI 894999 was consistent with those of other BET inhibitors. Due to minimal efficacy results, further evaluation of BI 894999 as monotherapy is not planned. © 2025 The Authors |
| Keywords: | adult; treatment outcome; treatment response; aged; major clinical study; overall survival; fatigue; neutropenia; advanced cancer; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; side effect; solid tumor; cancer staging; colorectal cancer; progression free survival; gene expression; anemia; nuclear protein; nausea; stomatitis; thrombocytopenia; delirium; inflammation; cohort analysis; alanine aminotransferase blood level; aspartate aminotransferase blood level; asthenia; dyspnea; febrile neutropenia; loading drug dose; pneumonia; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; acute kidney failure; hospitalization; single drug dose; sepsis; open study; alkaline phosphatase blood level; seizure; time to maximum plasma concentration; maximum tolerated dose; muscle spasm; hematoma; urine retention; epistaxis; dose calculation; tumor bleeding; plasma concentration-time curve; larynx disorder; diffuse large b-cell lymphoma; platelet count; dysgeusia; maintenance drug dose; small cell lung cancer; lung hemorrhage; decreased appetite; phase 1 clinical trial (topic); lymph node pain; troponin; testis carcinoma; diffuse large b cell lymphoma; dose escalation; troponin t; multiple drug dose; body weight loss; human; male; female; article; metastatic castration resistant prostate cancer; ecog performance status; maximum concentration; bladder distension; coronavirus disease 2019; bromodomain and extraterminal domain inhibitor; dose-limiting toxicities; amredobresib |
| Journal Title: | ESMO Open |
| Volume: | 10 |
| Issue: | 5 |
| ISSN: | 2059-7029 |
| Publisher: | European Society for Medical Oncology |
| Date Published: | 2025-05-01 |
| Start Page: | 104499 |
| Language: | English |
| DOI: | 10.1016/j.esmoop.2025.104499 |
| PROVIDER: | scopus |
| PMCID: | PMC12005229 |
| PUBMED: | 40203516 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
