AstraZeneca recently announced that the positive high-level results from the head-to-head ELEVATE-RR Phase 3 trial showed that in high-risk adult patients with chronic lymphocytic leukemia (CLL) who have previously received treatment, its targeted anticancer drug Calquence Compared with AbbVie/J&J Imbruvica (ibrutinib), (acalabrutinib) has non-inferiority in terms of progression-free survival (PFS) and reached the primary endpoint of the study.
In addition, the trial reached a key secondary endpoint of safety: Compared with the Imbruvica treatment group, the incidence of atrial fibrillation in the Calquence treatment group was statistically significantly lower. Atrial fibrillation is an irregular heart rate that can increase the risk of stroke, heart failure, and other heart-related complications. Further grading tests showed that there was no difference in infections of grade 3 or higher or Richter conversion. The overall survival shows a descriptive trend that is numerically favorable. In general, the safety and tolerability of Calquence are consistent with the situation in the broader Calquence clinical development plan.
It is worth mentioning that ELEVATE-RR is the first phase III trial comparing two Bruton tyrosine kinase (BTK) inhibitors in the treatment of CLL patients. CLL is the most common type of leukemia in adults. Patients diagnosed with high-risk CLL may experience rapid deterioration. Calquence is a new generation of selective BTK inhibitors, and Imbruvica is the world's first BTK inhibitor on the market.
ELEVATE-RR is a randomized, multi-center, open-label phase 3 non-inferiority trial. The enrolled patients were previously treated CLL patients with high-risk characteristics (17p deletion and/or 11q deletion). In the study, 533 patients were randomly (1:1) divided into 2 groups. One group received Calquence treatment (100 mg orally, 2 times a day), and the other group received Imbruvica (420 mg orally, once a day) until the disease progressed or Unacceptable toxicity occurs. The primary endpoint of the trial was PFS (non-inferiority, tested after 250 events) assessed by an independent review committee. Secondary endpoints include the incidence of atrial fibrillation, the incidence of grade 3 or higher infections caused by treatment, the incidence of Richter transformation (a condition in which CLL transforms into malignant lymphoma), and overall survival.
The data from the trial will be announced at an upcoming medical conference and shared with regulatory agencies.
José Baselga, Executive Vice President of Oncology Research and Development of AstraZeneca, said: “After more than 40 months of follow-up, today’s results confirm that Calquence has demonstrated superior safety in atrial fibrillation with non-inferior efficacy. All data confirms We have confidence in Calquence’s favorable return and risk characteristics."
Calquence was approved by the U.S. FDA for accelerated marketing in October 2017. The indications include: (1) For adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have previously received at least one therapy; (2) Use For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small cell lymphoma (SLL).
Calquence's active pharmaceutical ingredient is acalabrutinib, which is a next-generation, highly selective, potent, covalent Bruton tyrosine kinase (BTK) inhibitor that inhibits BTK through permanent binding. BTK is a key regulator of the B cell receptor (BCR) signaling pathway. It is widely expressed in different types of hematological malignancies and participates in the proliferation, transport, chemotaxis and adhesion of B cells. Therefore, it is important for the treatment of hematological malignancies. Target. In preclinical studies, acalabrutinib showed minimal off-target effects.
Currently, Calquence is being developed for a variety of B-cell blood cancers, including CLL, MCL, diffuse large B-cell lymphoma (DLBCL), Waldenstrom macroglobulinemia (WM), follicular lymphoma (FL), Multiple myeloma and other hematological malignancies.
Calquence's mechanism of action is the same as AbbVie/J&J's blockbuster blood cancer drug Imbruvica (ibrutinib), which is the first BTK inhibitor approved globally. Since its first approval in November 2013, Imbruvica has been approved for as many as 11 therapeutic indications in 6 disease areas, and global sales have been rising sharply. In June last year, the pharmaceutical market research organization EvaluatePharma released a report predicting that with the continuous market penetration and increasing indications, Imbruvica's sales in 2026 will reach 10.722 billion US dollars, becoming the world's fifth best-selling drug.