Article révisé par les pairs
Résumé : 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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