AstraZeneca's BTK Inhibitor Calquence Demonstrates 97% ORR in Treatment-Naïve CLL Patients at 4 Years in Phase II Trial

June 14, 2020 /Bio ValleyBIOON/ --AstraZeneca(AstraZeneca) recently announced at the 25th Annual Meeting of the European Hematology Association (EHA) the results of Calquence (acalabrutinib), a targeted anticancer drug, as first-line monotherapy for chronic lymphocyticLeukemiaDetailed results from the Phase II, single-arm ACE-CL-001 trial in patients with chronic lymphocytic leukemia (CLL), as well as long-term efficacy and tolerability data from the Phase III ASCEND trial of Calquence in patients with relapsed or refractory CLL. The results demonstrated that first-line monotherapy with Calquence in treatment-naïve CLL patients achieved a 4-year overall response rate (ORR) of up to 97%, while the 18-month survival rate in patients with relapsed/refractory CLL reached up to 88%, accompanied by a favorable long-term safety profile.

The ACE-CO-001 trial was conducted in previously untreated CLL patients to investigate the efficacy and safety of Calquence (100 mg twice daily [n=62] or 200 mg once daily [n=37]). On May 1, 2015, patients receiving the 200 mg dosing regimen were switched to the 100 mg dosing regimen.

Data showed that with a median follow-up of more than 4 years (4.4 years), 86% of CLL patients were still receiving Calquence as first-line monotherapy. The data indicated an overall response rate (ORR) of 97% (complete response rate [CR] = 7%, partial response rate [PR] = 90%). In the subgroup of patients with high-risk disease features, the ORR was 100%, including those with genomic aberrations (del(17p) [n=9] and TP53 mutation [n=9]), immunoglobulin mutational status (unmutated IGHV [n=57]), and complex karyotype (n=12). Lymph node disease decreased in all patients (n=97). Safety results showed no new long-term issues.

The ASCEND study is a global, randomized, multicenter, open-label Phase III trial conducted in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), investigating the efficacy and safety of Calquence (100 mg twice daily) versus investigator’s choice of rituximab plus idelalisib (IdR) or rituximab plus bendamustine (BR).

The final analysis of the study showed that at 18 months of treatment, an estimated 82% of CLL patients in the Calquence treatment group remained alive and free from disease progression, compared to an estimated 48% of patients treated with rituximab combined with idelalisib or bendamustine. Detailed results are as follows:

Richard R. Furman, Director of the CLL Research Center at Weill Cornell Medicine, stated, “These data indicate that Calquence presents no new safety concerns and confirm that the drug can safely provide meaningful long-term clinical benefits for patients with previously untreated (first-line), relapsed, or refractory CLL. Calquence will offer an important and rational treatment option for the CLL patient population.”

AstraZenecaTumorJosé Baselga, Executive Vice President of Research and Development, stated, “These long-term data reaffirm that Calquence provides durable remission with a favorable safety profile for patients with CLL. Patients with CLL are typically aged 70 years or older and have comorbidities, often requiring long-term treatment, which makes sustained safety and efficacy highly relevant to their quality of life.”

The results of the Phase II ACE-CL-001 trial provided the rationale for conducting the pivotal Phase III ELEVATE TN trial, which, together with the results of the Phase III ASCEND trial, laid the foundation for the United StatesFDABasis for the Approval of Calquence for the Treatment of CLL or Small Lymphocytic Lymphoma (SLL)

The active pharmaceutical ingredient of Calquence is acalabrutinib, a highly selective, potent, covalent Bruton’s tyrosine kinase (BTK) inhibitor that acts by irreversibly binding to and inhibiting BTK. BTK is a key regulator of the B-cell receptor (BCR) signaling pathway and is widely expressed in various types of hematologic malignancies, where it plays a role in B-cell proliferation, trafficking, chemotaxis, and adhesion, making it a therapeutic target for hematologic malignancies.Tumorimportant target. In preclinical studies, acalabrutinib demonstrated minimal off-target effects.

Calquence was approved in the United States in October 2017FDAAccelerated approval for marketing; current indications include: (1) adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have previously received at least one therapy; (2) treatment of adult patients with CLL/SLL. Currently, Calquence is being developed for multiple B-cell hematologic cancers, including CLL, MCL, diffuse large B-cell lymphoma, Waldenström macroglobulinemia (WM), follicular lymphoma (FL), multiple myeloma, and other hematologic malignancies.TumorAstraZeneca has extremely high commercial expectations for Calquence, with peak sales projected to reach $5 billion!

Calquence shares the same mechanism of action as AbbVie/J&J’s blockbuster blood cancer drug Imbruvica (ibrutinib), the first BTK inhibitor approved globally. Since its initial approval in November 2013, Imbruvica has gained approval for up to 10 therapeutic indications across six disease areas, with global sales showing a steady upward trend. The pharmaceutical market research firm EvaluatePharma previously released a report predicting that Imbruvica’s global sales would reach $9.5 billion in 2024, making it the fifth best-selling drug worldwide. (Bioon.com)

Original Source: Calquence showed long-term efficacy and tolerability for patients with chronic lymphocytic leukaemia in two trials