The agency’s decision was based on promising interim results from two ongoing Phase 3 clinical trials, the ELEVATE-TN (NCT02475681) and ASCEND (NCT02970318) studies, which compared Calquence to standard therapies, either alone or in a combination.
CLL/SLL occurs when B-cells, a type of immune cell, transform into cancer cells and grow in excess. Calquence can bind to and inhibit the Bruton tyrosine kinase protein, which helps to drive the growth of these cells. By blocking this growth-inducing signal, the drug helps to control cancer’s spread and to kill tumor cells.
ELEVATE-TN is a randomized, multicenter and open-label trial assessing the safety and efficacy of Calquence in patients with previously untreated CLL. A total of 535 people were randomized to either 100 mg of Calquence twice daily, Calquence in combination with Gazyva (obinutuzumab), or Gazyva in combination with chlorambucil (a chemotherapy), a current standard-of-care combination, serving as a comparator arm.
ASCEND is also a randomized, multicenter and open-label study assessing Calquence’s efficacy, but in patients with relapsed or refractory CLL. The trial assigned 310 people to either 100 mg of Calquence twice daily, or to Rituxan (rituximab) in combination with Zydelig (idelalisib) or bendamustine (a chemotherapy).
The primary goal of both trials is progression-free survival, or the length of time during and after treatment that a patient lives without disease worsening. Secondary objectives include overall survival, response rate and adverse events.
Both trials showed that Calquence either alone, or in combination with Gazyva in ELEVATE-TN, led to a clinically meaningful improvement in progression-free survival, reducing the risk of disease progression or death compared to the other treatment regimes tested in these CLL patients.
In the ELEVATE-TN trial, the risk of disease progression or death was significantly lower both in patients who received Calquence in combination with Gazyva (by 90%), and in those given Calquence as monotherapy (by 80%).
The median time for disease progression in patients treated with chlorambucil plus Gazyva was 22.6 months. This measure, however, had not yet been reached for patients treated either with Calquence as a monotherapy or in combination with Gazyva.
The safety and tolerability of Calquence in both trials were consistent with its established profile. The most common side effects were infection in the monotherapy and Calquence plus Gazyva group, and neutropenia (low white blood cell counts) in the comparator group.
“Tolerability remains an issue in the current treatment landscape of chronic lymphocytic leukaemia, which may require ongoing therapy for many years,” Jeff Sharman, director of research at Willamette Valley Cancer Institute, medical director of Hematology Research for The US Oncology Network, and a lead author of the ELEVATE-TN trial, said in a press release.
“In the ELEVATE-TN and ASCEND trials comparing Calquence to commonly used treatment regimens, Calquence demonstrated a clinically meaningful improvement in progression-free survival in patients across multiple settings, while maintaining its favourable tolerability and safety profile,” Sharman added.
In the ELEVATE-TN trial, 10% of patients on Calquence alone discontinued treatment as a result of side effects, compared to 11% and 14% of those treated with Calquence in combination with Gazyva or chlorambucil, respectively.
Side effects also resulted in a dose reduction of Calquence in 4% of patients treated with Calquence as monotherapy, and in 7% of those given Calquence plus Gazyva. In the control arm (Gazyva in combination with chlorambucil), adverse events led to a dose reduction of chlorambucil in 28% of the patients.
No dose reductions were observed for Gazyva.
“[T]oday’s approval of Calquence provides new hope for patients with one of the most common types of adult leukaemia, offering outstanding efficacy and a favourable tolerability profile,” said Dave Fredrickson, executive vice president of the Oncology Business Unit of AstraZeneca. “The chronic lymphocytic leukaemia patient population is known to face multiple comorbidities, and tolerability is a critical factor in their treatment.”