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

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2025-04-08 DOI:10.1016/j.esmoop.2025.104499

U.M. Lauer , A. Awada , S. Postel-Vinay , G.I. Shapiro , C. Thieblemont , S.A. Piha-Paul , P.K. Paik , D.R. Shepard , L.I. Docampo , R. Galot , S. Rottey , B. Sadrolhefazi , K. Marzin , H. Musa , P. Schöffski

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引用次数: 0

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.

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新型溴域和外端结构域抑制剂BI 894999在晚期实体瘤或弥漫性大b细胞淋巴瘤患者中的Ia/Ib期研究的最终结果

背景溴域和外域（BET）抑制剂已被证明对实体和血液系统恶性肿瘤有效。BI 894999是一种新型的口服BET抑制剂，已显示出临床前疗效。方法：这是一项开放标签、剂量发现研究，评估BI 894999治疗弥漫性大b细胞淋巴瘤(DLBCL；Ia期扩展)和实体肿瘤[结直肠癌（CRC）、睾丸核蛋白癌（NUT）、转移性去雄抵抗性前列腺癌（mCRPC）和小细胞肺癌（SCLC）]；Ib期队列]。主要终点是最大耐受剂量（MTD）期（Ia期）和治疗期（Ib期）的剂量限制性毒性（dlt）。结果18例DLBCL患者被纳入Ia期扩展组，79例实体瘤患者被纳入Ib期队列(SCLC, n = 12；CRC, n = 14；mCRPC, n = 11；NUT癌，n = 42)。4名患者在Ia期接受了dlt治疗，17名患者在Ib期接受了dlt治疗；最常见的是4级血小板减少症。DLBCL的MTD为1.5 mg（第1-14/21天）。1例（5.6%）DLBCL患者达到部分缓解（PR）， 3例（16.7%）病情稳定。42例NUT癌患者中，3例（7.1%）有缓解(完全缓解，n = 1；确认PR， n = 1；未确诊PR， n = 1)。其他实体肿瘤类型（n = 37）的应答包括1例确诊PR的mCRPC患者（2.7%）。结论BI 894999的安全性与其他BET抑制剂一致。由于疗效结果极低，未计划进一步评价BI 894999作为单药治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.