As part of Project Orbis, The FDA has approved acalabrutinib (Calquence) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
“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,” 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, adding that the agency’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international partners.
The project is a collaboration with the Australian Therapeutic Goods Administration (TGA) and Health Canada. “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.
The supplemental approval was based on 2 randomized clinical trials that compared acalabrutinib with other standard treatments.
In the randomized, multicenter, open-label, phase III ELEVANTE-TN (ACE-CL-007) trial, researchers 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, receiving either chlorambucil plus obinutuzumab; 100 mg of acalabrutinib twice daily in combination with obinutuzumab until disease progression or unacceptable toxicity; or single-agent acalabrutinib at 100 mg twice daily until disease progression or unacceptable toxicity.
Progression-free survival (PFS) in the acalabrutinib/obinutuzumab arm compared with the chlorambucil/obinutuzumab arm, as assessed by an independent review committee (IRC), serves the primary end point of the study. 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).
In the international, multicenter, open-label, phase III ASCEND trial, researchers evaluated the agent compared with rituximab (Rituxan) plus idelalisib (Zydelig) and bendamustine in 310 previously treated patients (median age, 67 years; range, 32-90) with CLL.
Patients were randomized 1:1 to receive single-agent acalabrutinib at 100 mg twice daily until disease progression or unacceptable toxicity (n = 155), or rituximab at 375 mg/m2 or 500 mg/m2 intravenously (IV) for up to 8 cycles in combination with idelalisib (n = 119) at 150 mg twice daily or IV bendamustine at 70 mg/m2 (n = 36) for 6 cycles.
The primary endpoint was PFS assessed by an IRC. 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.
In this study, 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). At 12 months, 88% of patients on acalabrutinib showed no disease progression compared with 68% in the control arm.
The acalabrutinib arm also showed improved PFS compared with the control group across all patient subgroups, including del(17p), TP53 mutation, and Rai stage.
Twelve-month OS rates were 94% and 91%, respectively, while IRC-assessed ORR also was not significantly different at 81% with acalabrutinib versus 75% in the control group (P <.22).
The most commonly reported all-grade adverse events occurring in the acalabrutinib arm were headache (22%), neutropenia (19%), diarrhea (18%), and anemia or cough (15% each).
Food and Drug Administration. FDA takes second action under international collaboration, approves new treatment option for patients with chronic lymphocytic leukemia. Available from: https://www.fda.gov/news-events/press-announcements/fda-takes-second-action-under-international-collaboration-approves-new-treatment-option-patients?utm_campaign=112119_PR_FDA%20takes%20second%20action%20under%20international%20collaboration&utm_medium=email&utm_source=Eloqua. Accessed: November 21, 2019.