Calquence(acalabrutinib)

Acalabrutinib (Calquence) is a drug for which an application was submitted on 14 October 2019. The international birth date for acalabrutinib was 31 October 2017. The NDA/BLA number for Calquence is 210259.

In clinical trials, acalabrutinib monotherapy demonstrated an overall response rate (ORR) of 83-84% in del 17p/TP53-mutated disease and 83-84% in del 17p/TP53-negative disease. Acalabrutinib in combination with obinutuzumab also showed an ORR of 83-84% in del 17p/TP53-mutated disease. The ORR in the control arm was 56%. The median progression-free survival (PFS) was not reached in some arms, while in others it was 22.6 months. The 12-month KM estimate for PFS was 95.9% and 84.6%, and the 36-month KM estimate was 89.6% and 31.3%. Complete response (CR) rates were 1% (Arm C) and 5% (Arm A). Partial response (PR) was observed in 74% of patients (Investigator's Choice).

Safety data from a pooled population of 1040 subjects with a median follow-up of 24.6 months indicated that serious adverse events (SAE) Grade ≥3 occurred in 50.8% in the IR arm and 25.7% in the BR arm. Treatment-emergent adverse events (TEAEs) leading to dose discontinuation were 10.7% in the acalabrutinib + obinutuzumab arm and 9.5% in the acalabrutinib monotherapy arm. Discontinuation rates for obinutuzumab were 6.5% in the acalabrutinib + obinutuzumab arm and 5.9% in the obinutuzumab + chlorambucil arm. TEAEs leading to chlorambucil discontinuation were 14.2%. No dose-limiting toxicities were reported.