Astrazeneca Calquence granted priority review by USFDA for previously untreated mantle cell lymphoma

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the first quarter of 2025.

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), resulting when B-lymphocytes mutate into malignant cells within a region of the lymph node known as the mantle zone. The disease is often diagnosed at advanced stages and remains largely incurable. It is estimated that there are more than 27,500 people living with MCL worldwide.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said, “The Priority Review acceptance reinforces the potential of Calquence to transform outcomes in untreated mantle cell lymphoma. Data from the ECHO trial showed Calquence plus chemoimmunotherapy significantly delayed disease progression and showed a trend to improved survival in patients with this currently incurable blood cancer. We are working closely with the FDA to provide patients this potential new treatment as soon as possible.”

The sNDA is being reviewed under Project Orbis, an initiative of the FDA which provides a framework for concurrent submission and review of oncology medicines among participating international partners to bring cancer treatments to patients around the world as early as possible.

Results from the ECHO Phase III trial recently were presented during the late-breaking oral session at the European Hematology Association (EHA) 2024 Hybrid Congress.

In the trial, Calquence plus bendamustine and rituximab reduced the risk of disease progression or death by 27% compared to standard-of-care (SoC) chemoimmunotherapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.57-0.94; p=0.016). The addition of Calquence to SoC provided almost 1.5 years of additional median progression free survival (mPFS) with mPFS of 66.4 months for patients treated with the Calquence combination versus 49.6 months with SoC.

Overall survival (OS) showed a favourable trend for the Calquence combination compared to SoC chemoimmunotherapy (HR 0.86; 95% CI 0.65-1.13; p=0.2743). The OS trend was sustained over time, although most patients in the SoC arm who needed subsequent therapy received a BTK inhibitor, mainly Calquence. The OS data were not mature at the time of this analysis, and the trial will continue to assess OS as a key secondary endpoint.

The ECHO trial was conducted during the COVID-19 pandemic, and prespecified PFS and OS analyses censoring for COVID-19 deaths were conducted to assess the impact of COVID-19 on the study outcome in alignment with FDA. After censoring for COVID-19 deaths, the PFS was further improved in both arms, with the Calquence combination reducing the risk of disease progression or death by 36% (HR 0.64; 95% CI; 0.48-0.84; p=0.0017). A favourable trend was seen for OS in this analysis for the Calquence combination, but OS data were not mature at the time of this analysis (HR 0.75; 95% CI 0.53-1.04; p=0.0797).

The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified.