AstraZeneca plc (LON: AZN) has today announced detailed results from the interim analysis of the Phase III ASCEND trial at the European Hematology Association Annual Congress in Amsterdam, showing Calquence (acalabrutinib) significantly prolonged the time patients live without disease progression in relapsed or refractory chronic lymphocytic leukaemia.
The ASCEND trial compared Calquence with the physician’s choice of rituximab combined with idelalisib (IdR) or bendamustine (BR) in patients with relapsed or refractory CLL.
At a median follow-up of 16.1 months, results from the trial showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) for patients treated with Calquence vs. IdR or BR, reducing the risk of disease progression or death by 69% (HR, 0.31; 95% CI, 0.20-0.49, p<0.0001). The median time without disease progression for patients treated with Calquence has not yet been reached vs. 16.5 months in the control arm. At 12 months, 88% of patients on Calquence showed no disease progression compared to 68% for the control arm. The safety and tolerability of Calquence was consistent with its established profile.
José Baselga, AstraZeneca PLC Executive Vice President, Oncology R&D said:
“These data add to the growing body of evidence to support the profile of Calquence as a selective BTK inhibitor that offers a chemotherapy-free treatment option with a favourable safety profile in chronic lymphocytic leukaemia, a life-threatening disease. These data, along with our recent positive results from the Phase III ELEVATE-TN trial in previously-untreated chronic lymphocytic leukaemia, will serve as the foundation for regulatory submissions later this year.”
Paolo Ghia, MD, Professor, Medical Oncology, Università Vita-Salute San Raffaele in Milan, and investigator of the ASCEND trial, said:
“This is the first randomised trial to directly compare a BTK inhibitor as monotherapy with standard chemoimmunotherapy or idelalisib and rituximab combinations. With a significant improvement in progression-free survival and a favourable safety profile, acalabrutinib may become an important choice for the treatment of patients with relapsed or refractory chronic lymphocytic leukaemia.”
Safety overview
| Most common (≥15%) | Calquence | IdR | BR | |||
| AEs, n (%) | (n=154) | (n=118) | (n=35) | |||
| Any | Grade ≥3 | Any | Grade ≥3 | Any | Grade ≥3 | |
| Headache | 34 (22%) | 1 (1%) | 7 (6%) | 0 | 0 | 0 |
| Neutropenia | 30 (19%) | 24 (16%) | 53 (45%) | 47 (40%) | 12 (34%) | 11 (31%) |
| Diarrhoea | 28 (18%) | 2 (1%) | 55 (47%) | 28 (24%) | 5 (14%) | 0 |
| Anaemia | 23 (15%) | 18 (12%) | 11 (9%) | 8 (7%) | 4 (11%) | 3 (9%) |
| Cough | 23 (15%) | 0 | 18 (15%) | 1 (1%) | 2 (6%) | 0 |
| Pyrexia | 19 (12%) | 1 (1%) | 21 (18%) | 8 (7%) | 6 (17%) | 1 (3%) |
| Fatigue | 15 (10%) | 2 (1%) | 10 (8%) | 0 | 8 (23%) | 1(3%) |
| Nausea | 11 (7%) | 0 | 15 (13%) | 1 (1%) | 7 (20%) | 0 |
| IRR | 0 | 0 | 9 (8%) | 2 (2%) | 8 (23%) | 1 (3%) |
Events of clinical interest for Calquence
| Atrial fibrillation | 8 (5%) | 2 (1%) | 4 (3%) | 1 (1%) | 1 (3%) | 1 (3%) |
| Bleeding | 40 (26%) | 3 (2%) | 9 (8%) | 3 (3%) | 2 (6%) | 1(3%) |
| Hypertension | 5 (3%) | 3 (2%) | 5 (4%) | 1 (1%) | 0 | 0 |
| SPM* excluding NMSC** | 10 (6%) | 5 (3%) | 3 (3%) | 0 | 1 (3%) | 1 (3%) |
*Secondary primary malignancy **Non-melanoma skin cancer.
AstraZeneca plc recently announced that the Phase III ELEVATE-TN trial met its primary endpoint at interim analysis in patients with previously-untreated CLL and that full results will be reported at a forthcoming medical meeting. Calquence is currently approved for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL) in the US, Brazil, the United Arab Emirates, and Qatar and is being developed for the treatment of CLL and other blood cancers.
