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.

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.