500O Trotabresib (CC-90010) combined with concomitant temozolomide (TMZ) plus radiotherapy (RT) and adjuvant TMZ in patients (pts) with newly diagnosed primary glioblastoma (ndGBM): Updated results from a phase Ib/II study

Trotabresib (TROTA) is a novel bromodomain and extraterminal protein inhibitor that has shown brain tumor tissue penetration, encouraging tolerability and preliminary efficacy in combination with standard of care (SOC) concomitant TMZ + RT and adjuvant TMZ in pts with ndGBM. We present long-term follow-up for part A (dose escalation) and an update on part B (expansion) of the ph 1b/2 CC-90010-GBM-002 study (NCT04324840). Study design has been previously described (Vieito et al. SNO 2022 . Abstr CTNI-21). Part B enrolled pts with IDH wild-type ndGBM; pts were randomized 2:1 to TROTA + SOC then maintenance TROTA (arm A) vs SOC alone (arm B). As of 20 Jan 2023, part A has closed with 32 pts enrolled (concomitant, n = 14; adjuvant, n = 18); part B has enrolled 136 pts (arm A, n = 91; arm B, n = 45). In part A, no new safety events were observed with longer follow-up; median follow-up was 21.6 mo (range 3.4–27.6). The most frequent grade (G) 3/4 treatment-related adverse event (TRAE) was thrombocytopenia (8/14 pts [57%] in the concomitant group and 9/18 pts [50%] in the adjuvant group). Efficacy in part A is shown in the table. At last follow-up, 8 pts (4 per group) remained on treatment, including 1 pt with ongoing complete response at cycle 24. In part B, the most common all-cause G 3/4 AE was thrombocytopenia occurring in 21/88 (24%) and 5/43 (12%) patients in arms A and B, respectively. TRAEs related to TROTA led to treatment discontinuation in 3 pts (arm A), and TRAEs related to TMZ led to discontinuation in 4 pts (2 in each arm); no treatment-related deaths reported. Enrollment of part B was recently completed; efficacy data are not yet mature. Addition of TROTA to SOC followed by maintenance TROTA in pts with ndGBM was well tolerated with no new safety signals in parts A and B, and promising efficacy in part A. Follow-up is ongoing.