The U.S Food and Drug Administration (FDA) gave accelerated approval to Calquence in 2017 to treat adults with mantle cell lymphoma (MCL) who had failed to respond adequately to at least one prior therapy.
It is being also studied as a monotherapy and combination therapy for solid tumors.
How does Calquence work?
MCL, CLL, and SLL are all types of B-cell non-Hodgkin’s lymphomas. B-cells are a type of white blood cell called lymphocytes and are responsible for combating infections or threats against the body by producing antibodies. B-cell lymphomas are characterized by the abnormal proliferation of B-cells turning into cancer cells.
Calquence is a highly selective and potent cell signal inhibitor that works by blocking the activity of a protein called Bruton’s tyrosine kinase, or BTK. BTK is a part of a pathway that helps B-cells stay alive and divide. By forming a strong covalent bond with BTK to block the transmission of cell survival signals within malignant B-cells, Calquence is designed to help kill and reduce the number of cancerous B-cells, slowing or stopping the progression of lymphoma.
Calquence in clinical trials
The FDA based its accelerated approval of Calquence on findings from a Phase 2 clinical trial (NCT02213926), called ACE-LY-004, that evaluated its effectiveness and safety. A total of 124 patients with relapsed (returning) or refractory (drug-resistant) MCL were recruited. Patients already treated with a BTK inhibitor were excluded from the trial. The trial measured the number of patients who experienced complete or partial tumor shrinkage after treatment (overall response rate).
The results showed that 40% of patients had a complete response, and 41% a partial response. The median duration of response was not yet reached at the time of analysis, with responses ongoing at more than 20 months.
ELEVATE-TN is a randomized trial assessing the safety and efficacy of Calquence treatment in patients with previously untreated CLL. A total of 535 people are randomized to either 100 mg of Calquence twice daily, Calquence in combination with Gazyva (obinutuzumab), or Gazyva in combination with the chemotherapy chlorambucil.
ASCEND is also a randomized trial assessing the efficacy of Calquence in relapsed or refractory CLL. A total of 310 participants are randomized to either 100 mg of Calquence twice daily, Rituxan (rituximab) in combination with Zydelig (idelalisib), or the chemotherapy agent bendamustine.
Both trials showed that Calquence reduces the relative risk of disease progression or death compared to the other treatments.
In ELEVATE-TN, specifically, the risk of disease progression or death was 90% lower in patients treated with Calquence and Gazyva, and 80% lower in those treated with Calquence alone. The median time for disease progression was 22.6 months in patients given Gazyva and chlorambucil; those treated with Calquence alone or in combination with Gazyva have not reached this measure.
The estimated study completion date is July 2021 for ELEVATE-TN and March 2020 for ASCEND.
Another Phase 3 clinical trial (NCT02972840) called ACE-LY-308 plans to evaluate Calquence in combination with bendamustine and Rituxan as a potential first-line treatment for patients with MCL. The trial is currently recruiting patients in the U.S., Australia, Europe, Canada, Hong Kong, Israel, Korea, New Zealand, Russia, and Ukraine.
The most common side effects reported with Calquence’s use include nausea, diarrhea, fatigue, and muscle pain, lower urinary tract infections, and treatment-related loss of white blood cells and platelets. Serious side effects include bleeding and irregular heartbeat.
Women who are breastfeeding should not take Calquence, because it may cause harm to a baby.
Calquence was also granted orphan drug designation by the FDA for the treatment of patients with MCL and by the European Commission (EC) for the treatment of patients with CLL, MCL, and WM.
Last updated: Dec. 2, 2019
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