ABBV‑744 in heavily pretreated MF: Phase Ib results

Results from a multicenter, open-label phase Ib study (NCT04454658), evaluating ABBV‑744, a selective bromodomain and extra-terminal domain inhibitor (BETi), as monotherapy in heavily pretreated patients with myelofibrosis (MF; N = 21), were published in Blood Advances by Mascarenhas et al. The primary endpoint was determination of ABBV‑744-related adverse events (AEs), including dose-limiting toxicities (DLTs). Secondary endpoints included the proportion of patients with a reduction in spleen volume of ≥35% (SVR35), the proportion of patients with a reduction in total symptom score of ≥50% (TSS50), objective response rate, and pharmacokinetic (PK) parameters. 

Key data: All patients experienced ≥1 treatment-emergent AE (TEAE), and 86% had ≥1 Grade 3–4 TEAE. The most frequent TEAEs of any grade were thrombocytopenia (67%), diarrhea (62%), anemia (48%), and nausea (33%). DLTs occurred in 52% of patients, most commonly thrombocytopenia (33%) and anemia (24%). SVR35 was achieved in 24%, 33%, and 33% of patients at Weeks 12, 24, and 36, respectively, and TSS50 was reported in 29%, 19%, and 14% of patients at Weeks 12, 24, and 36, respectively. The overall response rate (ORR) was 5%, and best overall responses included clinical improvement (33%) and stable disease (24%). 

Key learning: ABBV‑744 monotherapy demonstrated a safety profile consistent with pan-BETi agents, with cytopenias and gastrointestinal (GI) TEAEs as predominant toxicities. The limited clinical efficacy and tolerability challenges led to discontinuation of ABBV‑744 development in MF.