Japan Approves Acalabrutinib for Treatment-Naïve CLL

Japan’s Ministry of Health, Labor, and Welfare (MHLW) has approved acalabrutinib (Calquence) for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma.

The approval was based on findings from two clinical trials, including the phase 3 ELEVATE-TN trial (NCT02475681), in which acalabrutinib alone or combined with obinutuzumab (Gazyva) led to a significant improvement in progression-free survival (PFS) compared with chlorambucil and obinutuzumab.

Additionally, a phase 1 trial in Japanese patients with previously untreated CLL was also submitted to MHLW supporting the approval, with the trial showing an overall response rate (ORR) of 88.9% (95% CI, 63.2%-98.8%) with acalabrutinib alone and 100% (95% CI, 66.4%-100%) with acalabrutinib plus obinutuzumab.

“Results from ELEVATE-TN and our local Japanese trial confirm that [acalabrutinib] provides a significant improvement in PFS compared with chemotherapy-based combination of chlorambucil and obinutuzumab for patients with treatment-naïve CLL. [This] approval marks great progress for physicians and patients in Japan, as they can now be treated with [acalabrutinib] earlier in their treatment journey,” Koji Izutsu, MD, PhD, department head, Department of Hematology, National Cancer Center Hospital in Tokyo, Japan, said in a press release.

ELEVATE-TN is a randomized, multicenter, open-label phase 3 trial evaluating the safety and efficacy of acalabrutinib alone or in combination with obinutuzumab vs chlorambucil in combination with obinutuzumab in previously untreated patients with CLL. In the trial, 535 patients were randomly assigned 1:1:1 into three arms. Patients in the first arm received chlorambucil in combination with obinutuzumab. Patients in the second arm received acalabrutinib at 100mg twice daily until disease progression in combination with obinutuzumab. Patients in the third arm received acalabrutinib monotherapy at 100mg twice daily until disease progression.

The primary end point was PFS in the acalabrutinib /obinutuzumab arm compared to the chlorambucil/obinutuzumab arm, assessed by an independent review committee (IRC). A key secondary end point was IRC-assessed PFS in the acalabrutinib monotherapy arm compared with the chlorambucil/obinutuzumab arm. Other secondary end points included ORR, time to next treatment, overall survival, and investigator-assessed PFS. After interim analysis, assessments were by investigator only.

Updated results of the ELEVATE-TN after a median follow-up of approximately five years were presented in June 2022. These results showed that acalabrutinib maintained a statistically significant PFS benefit vs chlorambucil plus obinutuzumab, plus a safety and tolerability profile consistent with the known profile for acalabrutinib.

At a median follow-up of 58.2 months, acalabrutinib/obinutuzumab reduced the risk of disease progression or death by 89% (HR, 0.11; 95% CI, 0.07-0.16) and as a monotherapy by 79% (HR, 0.21; 95% CI. 0.15-0.30), compared with chlorambucil plus obinutuzumab.

“The approval of acalabrutinib in Japan for those with treatment-naïve CLL now offers more patients a next-generation BTK inhibitor that has proven longer-term efficacy and tolerability compared to standards of care. With this approval, people living with CLL in Japan can now potentially benefit from our medicine in an earlier setting,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, said.

Reference

Calquence approved in Japan for adults with treatment-naïve chronic lymphocytic leukaemia. News release. AstraZeneca. December 28, 2022. Accessed January 6, 2022. https://bit.ly/3Cw5ED0