On 21 November 2019, the US Food and Drug Administration (FDA) approved acalabrutinib (CALQUENCE, AstraZeneca) for adults with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL).
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The FDA, the Australian Therapeutic Goods Administration, and Health Canada collaborated on this review.
Approval was based on two randomised, actively controlled trials in patients with CLL: ELEVATE-TN (NCT02475681) and ASCEND (NCT02970318). Efficacy in both trials was based on progression-free survival (PFS) as assessed by independent review.
ELEVATE-TN randomised 535 patients with previously untreated CLL to one of three arms: acalabrutinib monotherapy, acalabrutinib plus obinutuzumab, or obinutuzumab plus chlorambucil. With a median follow-up of 28.3 months, PFS was significantly improved in both acalabrutinib arms. Compared to the obinutuzumab plus chlorambucil arm, the hazard ratio (HR) for PFS was 0.10 (95% CI: 0.06, 0.17; p < 0.0001) with acalabrutinib plus obinutuzumab and 0.20 (95% CI: 0.13, 0.30; p < 0.0001) with single agent acalabrutinib.
ASCEND randomised 310 patients with relapsed or refractory CLL after at least one prior systemic therapy to receive either acalabrutinib or investigator’s choice (either idelalisib plus a rituximab product, or bendamustine plus a rituximab product). With a median follow-up of 16.1 months, PFS was significantly longer in the acalabrutinib arm compared to the investigator’s choice arm (HR 0.31; 95% CI, 0.20, 0.49; p < 0.0001).
In both trials, median PFS had not been reached in the acalabrutinib arms. In addition, median overall survival had not been reached in any arm for either trial, with fewer than 15% of patients experiencing an event.
The most common adverse reactions (≥ 30%) of any grade in patients with CLL were anaemia, neutropenia, thrombocytopenia, headache, upper respiratory tract infection, and diarrhoea.
The recommended dose is 100 mg orally every 12 hours; swallow whole with water and with or without food.
Full prescribing information for CALQUENCE is available here.
This review used the Real-Time Oncology Review (RTOR) and Assessment Aid pilot programmes, which streamlined data submission prior to the filing of the entire clinical applications, and facilitated discussions among the regulatory agencies. These applications were approved four months prior to the FDA goal date. The FDA granted these applications Priority Review and Breakthrough Therapy designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate.