Acalabrutinib Receives Approval in China for Relapsed/Refractory Mantle Cell Lymphoma

Acalabrutinib (Calquence) has received conditional approval from the National Medical Products Administration in China for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy, representing the first approval for the next-generation BTK inhibitor in China.

The regulatory decision was based on findings from the global, phase 2 ACE-LY-004 trial (NCT02213926) in relapsed/refractory MCL and a phase 1/2 trial (NCT03932331) in Chinese patients with relapsed/refractory MCL and other B-cell malignancies.

At a median follow-up of 15.2 months, findings from the ACE-LY-004 trial demonstrated that patients experienced an investigator-assessed overall response rate (ORR) of 80.6% (95% CI, 72.6%-87.2%), with a complete response (CR) rate of 39.5% (95% CI, 30.9%-48.7%). In the Chinese trial, the ORR assessed via blinded independent central review (BICR) was 82.4% (95% CI, 65.5%-93.2%), with a CR rate of 35.3%.

“Mantle cell lymphoma progresses rapidly and responds poorly to conventional treatment such as immunochemotherapy. Before the emergence of BTK inhibitors, there were few satisfactory treatment options for patients,” Jun Zhu, chief physician in the Department of Lymphatic Oncology at Peking University Cancer Hospital in Beijing, stated in a press release. “The next-generation BTK inhibitor [acalabrutinib] has higher target selectivity, fewer side effects, and a higher response rate compared to currently available treatments. This approval of [acalabrutinib] in China can provide a new treatment option which can better benefit patients with this disease.”

ACE-LY-004 is an open-label, single-arm phase 2 trial evaluating acalabrutinib in adult patients with relapsed or refractory MCL. To be eligible for enrollment, patients must have had relapsed or refractory disease following 1 to 5 prior lines of therapy, no prior exposure to BTK or BCL-2 inhibitors, and an ECOG performance status of 2 or lower. Additionally, patients could not require treatment with warfarin or vitamin K antagonists.

Eligible patients received 100 mg of acalabrutinib twice daily until progressive disease (PD) or toxicity. ORR served as the primary end point of the study. Duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety were also evaluated.

The second trial was an open-label, multicenter study evaluating the efficacy, safety, and pharmacokinetic activity of acalabrutinib in Chinese patients with relapsed or refractory MCL and other advanced B-cell malignancies.

In phase 1, patients with relapsed or refractory B-cell malignancies received a single dose of 100 mg of oral acalabrutinib followed by a two-day washout period and subsequent treatment with 100 mg of the agent twice daily in 28-day cycles, until PD or treatment discontinuation. In phase 2, patients with relapsed or refractory MCL and an ECOG performance status of 2 or lower received 100 mg of acalabrutinib twice daily in 28-day cycles until PD or treatment discontinuation. The primary end point of the study was BICR-assessed ORR. Secondary end points were investigator-assessed ORR, BICR- and investigator-assessed time to response, DOR, PFS, OS, and safety.

Longer-term analysis from ACE-LY-004, which was conducted at 38.1 months, showed that patients who received acalabrutinib remained progression free for a median of 22 months, with a median OS of 59.2 months (95% CI, 36.5-not evaluable).

Additional data from the second trial conducted in China indicated that acalabrutinib reduced the risk of disease progression or death by 51.5% (95% CI, 33.3%-67.0%) at 12 months. The estimated 1-year DOR was 65.5% (95% CI, 66.6%-93.3%), and the median DOR was not reached.

In both trials, the safety and tolerability of acalabrutinib was similar to that reported in prior studies.

“This approval for [acalabrutinib] offers people living with mantle cell lymphoma in China an effective and tolerable new treatment option to help control their disease,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, stated in the press release. “As the first approval in China for [acalabrutinib], it is also an exciting step forward for AstraZeneca in blood cancers, enabling us to help more patients across the globe gain access to innovative treatments.”

Reference

Calquence granted first regulatory approval in China for adults with previously treated mantle cell lymphoma. News release. AstraZeneca. March 23, 2023. Accessed March 23, 2023. https://www.astrazeneca.com/media-centre/press-releases/2023