Phase III ELEVATE TN trial of Calquence monotherapy and combined with Gazyva shows improved PFS in chronic lymphocytic leukaemia.- AstraZeneca

AstraZeneca presented results from the interim analysis of the Phase III ELEVATE TN trial, showing that Calquence (acalabrutinib) combined with obinutuzumab or as monotherapy significantly improved progression-free survival (PFS) compared to chlorambucil plus obinutuzumab, a standard chemo-immunotherapy treatment, in patients with previously untreated chronic lymphocytic leukaemia (CLL). At a median follow-up of 28.3 months, Calquence in combination with obinutuzumab or as a monotherapy significantly reduced the risk of disease progression or death by 90% and 80%, respectively, vs. chlorambucil plus obinutuzumab.

In an exploratory analysis, Calquence in combination or alone demonstrated consistent PFS improvements across most pre-specified subgroups of patients with high-risk disease characteristics, including the unmutated immunoglobulin heavy-chain variable gene (IGHV), del(11q) and complex karyotype. Overall, the safety and tolerability profile of Calquence observed in the ELEVATE TN trial was consistent with its known profile.

Adverse events (AEs) led to treatment discontinuation in 11.2% of patients treated with Calquence in combination with obinutuzumab and 8.9% of patients treated with Calquence monotherapy versus 14.1% of patients treated with chlorambucil plus obinutuzumab. With over two years of follow-up, 79% of patients in both the Calquence-containing arms remain on Calquence as a monotherapy. In the Calquence combination arm (n=178), the most common AEs of any grade (at least 30%) included headache (39.9%), diarrhoea (38.8%) and neutropenia (31.5%). In the Calquence monotherapy arm (n=179), the most common AEs of any grade (at least 30%) included headache (36.9%) and diarrhoea (34.6%). In the chlorambucil plus obinutuzumab arm (n=169), the most common AEs of any grade (at least 30%) included neutropenia (45.0%), infusion-related reaction (39.6%) and nausea (31.4%). The Independent Review Committee (IRC)-assessed results were presented at the 2019 American Society of Hematology Annual Meeting and Exhibition.