AstraZeneca's BTK Inhibitor Calquence Demonstrates Durable Efficacy in Mantle Cell Lymphoma with 81% Overall Response Rate at Three Years

December 06, 2020 News /Bio ValleyBIOON/ ---AstraZeneca(AstraZeneca) recently announced the long-term follow-up (3-year) results of the Phase II ACE-LY-004 study (n=124) evaluating the targeted anticancer drug Calquence (acalabrutinib) in patients with relapsed or refractory mantle cell lymphoma (MCL) at the 62nd Annual Meeting of the American Society of Hematology (ASH).

Mantle cell lymphoma (MCL) is a typical aggressive, rare non-Hodgkin lymphoma (NHL), accounting for approximately 6% of all NHL cases, and is most commonly seen in men in their early 60s.. Since its market launch in 2017,Calquence has become an important chemotherapy-free treatment option for relapsed or refractory MCL and has been rapidly adopted by the clinical community and patient population.

ACE-LY-004 is an open-label, single-arm Phase II study conducted in 124 adult patients with relapsed or refractory mantle cell lymphoma (MCL). These patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of ≤2, experienced relapse or refractoriness after receiving 1–5 prior therapies, were previously untreated with BTK or BCL-2 inhibitors, and did not require warfarin or vitamin K antagonists. In the study, patients received Calquence 100 mg twice daily until disease progression or unacceptable toxicity.

Data presented at the meeting showed that, with a median follow-up of 38.1 months (range: 0.3–59.5), the overall response rate (ORR) was 81% (95% CI: 74, 88), the complete response rate (CR) was 48% (95% CI: 39, 57), the median duration of response (DOR) was 28.6 months (95% CI: 17.5, 39.1), the predicted 36-month sustained response rate was 41.9% (95% CI: 31.7, 51.8), the median progression-free survival (PFS) was 22 months (95% CI: 16.6, 33.3), the predicted 36-month progression-free survival rate was 37.2% (95% CI: 28.2, 46.1), and the median overall survival (OS) had not been reached. Safety and tolerability were consistent with previously reported findings.

At a median follow-up of 38.1 months (range: 0.3–59.5), 55 patients (44%) were either continuing treatment (24 patients) or continuing survival follow-up (31 patients). In the final analysis at month 26, the safety profile remained largely unchanged, with only 14 patients (11%) discontinuing treatment due to adverse events (AEs).

In addition,An exploratory analysis of 30 patients who met the criteria for minimal residual disease (MRD) assessment showed that 6 patients (20%) achieved complete remission with undetectable MRD (uMRD, i.e., MRD-negative) and maintained uMRD at the final assessment.

During the additional one-year follow-up period, adverse events in the trial remained largely unchanged. The most common adverse events of any grade (occurring in ≥20% of patients) included headache (39%), diarrhea (37%), fatigue (30%), cough (23%), myalgia (22%), and nausea (22%), which were predominantly Grade 1/2. Grade 3/4Adverse Reactionsincluding neutropenia (11%),Anemia(10%) and pneumonia (6%).

Overall, 16 patients (13%) experienced cardiac adverse events (11 of whom had cardiac risk factors), with 3 cases occurring in the final year of follow-up (2 of which were Grade 3/4). Overall, 6 patients (5%) experienced Grade 3/4 cardiac adverse events. One patient experienced a Grade 3/4 event in the past year.Hypertension(Any grade, n=5 [4%]; Grade 3/4, n=2 [2%]); five patients experienced bleeding adverse events in the past year (any grade, n=46 [37%]). Three patients had Grade 3/4 infections in the past year.

Dr. Michael L. Wang, Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and Principal Investigator of the ACE-LY-004 study, stated, “Mantle cell lymphoma (MCL) is an aggressive and difficult-to-treat hematologic cancer that is typically diagnosed at advanced stages”Diagnosisemerge and often develop resistance to treatment. These data demonstrate that patients treated with Calquence achieve deepening responses over time, while the safety profile remains largely unchanged, including low incidences of Grade 3/4 events, cardiac events, and bleeding events, which is particularly important in this patient population.”

AstraZenecaTumorJosé Baselga, Executive Vice President of Research and Development, stated, “These results add to the growing body of evidence demonstrating that Calquence can provide durable remissions in patients for more than three years. Calquence is an important chemotherapy-free treatment option for relapsed or refractory mantle cell lymphoma and has been rapidly adopted by the clinical and patient communities.”

Preliminary results from the Phase II ACE-LY-004 study were presented on December 9, 2017, at the 59th ASH Annual Meeting and Exposition, as a U.S.FDABasis for the Initial Approval of Calquence for the Treatment of Adult Patients with Mantle Cell Lymphoma (MCL) Who Have Received at Least One Prior Therapy. Calquence has also been approved for this indication in many other countries. The U.S. indication for MCL was approved under the accelerated approval program based on overall response rate data. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Calquence was approved in the United States in October 2017FDAAccelerated approval for marketing, with indications including: (1) adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have previously received at least one therapy; (2) for the treatment of chronic lymphocyticLeukemia(Chronic Lymphocytic Leukemia [CLL] or Small Lymphocytic Lymphoma [SLL]) adult patients.

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 participates in B-cell proliferation, trafficking, chemotaxis, and adhesion, thereby representing a therapeutic target for hematologic malignancies.Tumorimportant target. In preclinical studies, acalabrutinib demonstrated minimal off-target effects.

Currently, Calquence is being developed for the treatment of various B-cell hematologic malignancies, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), Waldenström macroglobulinemia (WM), follicular lymphoma (FL), multiple myeloma, and other hematologic malignancies.Tumor。

Calquence shares the same mechanism of action as AbbVie/J&J’s blockbuster hematologic malignancy drug Imbruvica (ibrutinib), the first BTK inhibitor approved globally. Since its initial approval in November 2013, Imbruvica has gained approval for up to 11 therapeutic indications across six disease areas, with global sales rising steadily. In late June this year, the pharmaceutical market research firm EvaluatePharma released a report predicting that, driven by continuous market penetration and an expanding label, Imbruvica’s sales will reach $10.722 billion in 2026, making it the fifth best-selling drug worldwide. (Bioon.com)

Original Source: Calquence Shows Long-Term Efficacy and Tolerability at Three Years for Patients with Relapsed or Refractory Mantle Cell Lymphoma