AstraZeneca Drug Regimen Improves PFS in First-Line Rare Blood Cancer

Rare Daily Staff

Positive high-level results from an interim analysis of the ECHO phase 3 trial showed AstraZeneca’s Calquence in combination with standard-of-care chemoimmunotherapy, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival versus standard of care in previously untreated adult patients with mantle cell lymphoma.

A trend was observed in favor of Calquence plus chemoimmunotherapy for the secondary endpoint of overall survival (OS). The OS data were not mature at the time of this analysis and the trial will continue to assess OS.

Mantle cell lymphoma (MCL) is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), often diagnosed as a late-stage disease, resulting when B-lymphocytes mutate into malignant cells within a region of the lymph node known as the mantle zone.

Calquence (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK) that binds covalently to BTK, thereby inhibiting its activity. In B cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion. It is approved for the treatment of adult patients with MCL who have received at least one prior therapy. This indication is approved under accelerated approval based on overall response rate with continued approval contingent upon verification and description of clinical benefit in confirmatory trials.

“These impactful results in mantle cell lymphoma show that bringing Calquence to the first-line setting significantly delays disease progression and, for the first time, shows potential to extend survival,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca. “The improvement in progression-free survival together with the differentiated safety profile of Calquence are both important as we strive to transform outcomes earlier in the course of disease treatment.”

ECHO is a randomized, double-blind, placebo-controlled, multi-center phase 3 trial evaluating the efficacy and safety of Calquence plus bendamustine and rituximab compared to standard of care chemoimmunotherapy (bendamustine and rituximab) in adult patients at or over 65 years of age (n=598) with previously untreated MCL.

In the experimental arms, patients were randomized 1:1 to receive either Calquence or placebo administered orally twice per day, on days 1 and 2 of each 28-day treatment cycle, plus bendamustine on days 1 and 2 and rituximab on day 1. After six cycles of Calquence or placebo in combination with bendamustine and rituximab, patients receive Calquence or placebo plus maintenance rituximab for two years and then either Calquence or placebo only until disease progression.

The primary endpoint is progression-free survival and key secondary endpoints include overall survival, overall response rate, duration of response and time to response. The trial includes 27 countries across North and South America, Europe, Asia and Oceania.

The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified. The data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

Calquence has been used to treat more than 80,000 patients worldwide and is approved for the treatment of CLL and small lymphocytic lymphoma (SLL) in the United States, approved for CLL in the European Union and many other countries worldwide and approved in Japan and China for relapsed or refractory CLL and SLL.

CALQUENCE is also approved in the United States, China, and several other countries for the treatment of adult patients with MCL who have received at least one prior therapy. CALQUENCE is not currently approved for the treatment of MCL in Japan or the European Union.

Photo: Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca