AstraZeneca and its haematology research and development centre of excellence, Acerta Pharma, announced that the US Food and Drug Administration (FDA) has granted accelerated approval to Calquence (acalabrutinib). Calquence is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
Calquence is approved under the FDA’s accelerated approval pathway, based on overall response rate, which allows for earlier approval of medicines that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Pascal Soriot, Chief Executive Officer of AstraZeneca, said: “The accelerated approval of Calquence is a landmark moment for our company. It provides an exciting new treatment option for patients with mantle cell lymphoma and marks the first approval of a medicine that will be the cornerstone of our presence in haematology. Furthermore, today’s approval demonstrates our commitment to scientific leadership in Oncology and reinforces our progress towards returning to growth.”
Michael L. Wang, MD, Professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, and Principal Investigator of the ACE-LY-004 MCL clinical trial, said: “The acalabrutinib approval represents an important development for patients currently battling mantle cell lymphoma, an aggressive type of blood cancer that is typically diagnosed at an advanced stage and associated with a high relapse rate. In addition to the overall response rate, the high complete response rate of 40% seen in this trial illustrates the potential of acalabrutinib to help patients achieve a deep response.”
Summary of key efficacy results as assessed by Independent Review Committee (IRC) from the ACE-LY-004 trial, a Phase II open-label, single-arm clinical trial in 124 adult patients with relapsed or refractory MCL:
| Efficacy Measure | Result |
| Overall Response Rate | 80% (95% CI: 72, 87) |
| Complete Response | 40% (95% CI: 31, 49) |
| Partial Response | 40%
(95% CI: 32, 50) |
Per Lugano classification, CI = Confidence interval
In the ACE-LY-004 trial, the most common adverse reactions (≥20%) of any grade were anaemia (46%), thrombocytopoenia (44%), headache (39%), neutropoenia (36%), diarrhoea (31%), fatigue (28%), myalgia (21%) and bruising (21%). Haematological events were based on laboratory measurements and adverse reactions.
Dosage reductions or discontinuation due to any adverse reaction were reported in 1.6% and 6.5% of patients, respectively.1 Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.
These data demonstrate the potential impact that Calquence could have on the management of previously-treated MCL. Calquence is not approved for use outside this labelled indication in the US.
Meghan Gutierrez, Chief Executive Officer, Lymphoma Research Foundation, said: “Relapse is common in mantle cell lymphoma patients and represents disease progression. When patients learn there is a new treatment option available for their disease, it brings great hope and an opportunity to participate in shared decision making with their healthcare team.”
Full results from the ACE-LY-004 clinical trial have been submitted for presentation at a forthcoming medical meeting. This will be the first MCL trial data to be presented from the Calquence development programme, which includes both monotherapy and combination therapies in a broad range of blood cancers and solid tumours. Calquence is also being evaluated in combination with bendamustine and rituximab as a potential 1st-line treatment for patients with MCL in the Phase III ACE-LY-308 clinical trial.
Source: AstraZeneca