The FDA has approved acalabrutinib (Calquence) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
The approval, which was done under the FDA’s Project Orbis initiative, was based on 2 phase III randomized trials—ELEVATE-TN and ASCEND.
“Today, as part of a U.S., Australian and Canadian collaboration known as Project Orbis, the U.S. approved a new treatment option for those living with chronic lymphocytic leukemia or small lymphocytic lymphoma. The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international partners,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press release.
“We are pleased to continue working alongside our Australian and Canadian colleagues to facilitate new treatment options for patients and the FDA looks forward to working with other countries in future application reviews,” added Pazdur.
In the randomized, multicenter, open-label, phase III ELEVANTE-TN (ACE-CL-007) trial, investigators evaluated the safety and efficacy of acalabrutinib
alone or in combination with obinutuzumab (Gazyva) versus chlorambucil/obinutuzumab in 535 treatment-naïve patients with CLL. Patients were randomized (1:1:1) into 3 arms: chlorambucil plus obinutuzumab, 100 mg of acalabrutinib twice daily in combination with obinutuzumab until disease progression or unacceptable toxicity, and acalabrutinib, or single-agent acalabrutinib at 100 mg twice daily until disease progression or unacceptable toxicity.
The primary endpoint is progression-free survival (PFS) in the acalabrutinib/obinutuzumab arm compared with the chlorambucil/obinutuzumab arm, as assessed by an independent review committee (IRC). Secondary endpoints included IRC-assessed PFS in the acalabrutinib-alone arm versus chlorambucil/obinutuzumab, as well as objective response rate (ORR), time to next treatment, and overall survival (OS).
It was previously reported that single-agent acalabrutinib showed a statistically significant and clinically meaningful improvement in PFS compared with obinutuzumab/chlorambucil. Full findings of ELEVATE-TN are slated to be presented at an upcoming medical meeting.
The primary endpoint was PFS assessed by an IRC, and key secondary endpoints included physician-assessed PFS, IRC- and physician-assessed ORR and duration of response, as well as OS, patient-reported outcomes and time to next treatment.
Results showed that, at a median follow-up of 16.1 months, the median PFS with acalabrutinib was not reached compared with 16.5 months in the control arms (HR, 0.31; 95% CI, 0.20-0.49; P
<.0001), translating to a 69% reduction in the risk of progression or death. At 12 months, 88% of patients on acalabrutinib showed no disease progression compared with 68% in the control arm.
Data also showed that PFS was improved with acalabrutinib compared with control across all patient subgroups, including del(17p), TP53
mutation, and Rai stage. Moreover, 12-month OS rates were 94% and 91%, respectively. IRC-assessed ORR also was not significantly different at 81% with acalabrutinib versus 75% with control (P
Regarding safety, the most commonly reported all-grade AEs occurring in ≥15% of patients treated with acalabrutinib were headache (22%), neutropenia (19%), diarrhea (18%), and anemia or cough (15% each).
Grade ≥3 AEs with acalabrutinib, rituximab/idelalisib, and bendamustine rituximab (BR) included neutropenia (16% vs 40% vs 31%, respectively), anemia (12% with acalabrutinib vs 9% with BR), and pneumonia (5% with acalabrutinib), diarrhea (24% with idelalisib/rituximab), and constipation (6% with BR).
Acalabrutinib is also approved by the FDA for the treatment of patients with relapsed/refractory mantle cell lymphoma.
A version of this article originally appeared on OncLiveâ as, “FDA Approves Acalabrutinib for CLL”.