General Information

Calquence (acalabrutinib) is a small molecule Bruton tyrosine kinase inhibitor.

Calquence is specifically indicated for the following conditions:

for treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy

for the treatment of adult patients with CLL or SLL

Calquence is supplied as a capsule for oral administration. Advise patients to swallow capsule whole with water. Advise patients not to open, break or chew the capsules. Calquence may be taken with or without food. If a dose is missed by more than 3 hours, it should be skipped and the next dose should be taken at its regularly scheduled time. Extra capsules of Calquence should not be taken to make up for a missed dose.

The recommended dose is as follows:

Calquence monotherapy:

100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity.

Calquence in Combination with Obinutuzumab:

For patients with previously untreated CLL or SLL, the recommended dose is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity. Start Calquence at Cycle 1 (each cycle is 28 days). Start obinutuzumab at Cycle 2 for a total of 6 cycles and refer to the obinutuzumab prescribing information for recommended dosing. Administer Calquence prior to obinutuzumab when given on the same day.

Mechanism of Action

Calquence (acalabrutinib) is a small molecule Bruton tyrosine kinase inhibitor. Acalabrutinib and its active metabolite, ACP-5862, form a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B cell antigen receptor (BCR) and cytokine receptor pathways. In B cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.

Indication 1 - previously treated Mantle cell lymphoma

approved November 2017

Clinical Trial Results

Calquence was granted accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. A phase II open label study enrolled a total of 124 patients with MCL who had received at least one prior therapy. Calquence was administered orally at 100 mg twice daily until disease progression or unacceptable toxicity. Tumor response was assessed according to the Lugano Classification for Non-Hodgkin’s lymphoma (NHL). The major efficacy outcome of the trial was overall response rate (ORR) and the median follow-up was 15.2 months. The ORR was achieved by 81% and 40% showed a Complete Response.

Indication 2 - chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)

approved November 2019

Clinical Trial Results

The FDA approval of Calquence for CLL and SLL was based on the interim analyses of two Phase III clinical trials, ELEVATE-TN in patients with previously untreated CLL and ASCEND in patients with relapsed or refractory CLL. Together, the trials showed that Calquence in combination with obinutuzumab or as a monotherapy significantly reduced the relative risk of disease progression or death versus the comparator arms in both 1st-line and relapsed or refractory CLL. In ELEVATE-TN, results showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients treated with either Calquence in combination with obinutuzumab or Calquence monotherapy versus chlorambucil chemotherapy plus obinutuzumab, a current standard-of-care combination used in the control arm. In the Calquence combination arm, risk of disease progression or death was reduced by 90% and in the monotherapy arm it was reduced by 80%. The median time to disease progression for patients treated with Calquence in combination with obinutuzumab or as a monotherapy has not yet been reached versus 22.6 months for chlorambucil plus obinutuzumab.