On November 21, 2019, the FDA accelerated the approval of acalabrutinib (Calquence; AstraZeneca) for adults with chronic lymphocytic leukemia (CLL) or with small lymphocytic lymphoma. This drug was approved 4 months earlier than the FDA PDUFA date. The FDA used its priority review for these 2 indications and granted acalabrutinib a breakthrough therapy designation for these indications.
This approval was done under Project Orbis, a new initiative by the FDA’s Oncology Center of Excellence. Project Orbis provides a framework for the concurrent submission and review of cancer drugs among international partners. The FDA, the Australian Therapeutic Goods Administration, and Health Canada collaborated on this review.
“Today, as part of a US, Australian, and Canadian collaboration known as Project Orbis, the US 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,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.
The approval was based on results of 2 randomized, actively controlled clinical trials.
The ELEVATE-TN study included 535 newly diagnosed patients with CLL who were randomized to 1 of 3 arms: acalabrutinib monotherapy, acalabrutinib plus obinutuzumab, or obinutuzumab plus chlorambucil. With a median follow-up of 28.3 months, the hazard ratio (HR) for progression-free survival (PFS) was 0.10 (95% confidence interval [CI], 0.06-0.17; P <.0001) with acalabrutinib plus obinutuzumab and 0.20 (95% CI, 0.13-0.30; P <.0001) with acalabrutinib monotherapy compared with obinutuzumab plus chlorambucil.
The ASCEND study randomized 310 patients with relapsed or refractory CLL who received at least 1 systemic therapy to acalabrutinib or to the investigator’s choice of treatment (idelalisib plus rituximab therapy, or bendamustine plus rituximab therapy). With a median follow-up of 16.1 months, the PFS was significantly longer in the acalabrutinib monotherapy arm compared with the investigator’s choice arm (HR, 0.31; 95% CI, 0.20-0.49; P <.0001).
In both studies, with a median follow-up of 28.3 months, the median PFS had not been reached in the acalabrutinib arm, and the median overall survival had not been reached in any arm.
The most common adverse reactions (≥30%) of any grade in patients with CLL were anemia, neutropenia, thrombocytopenia, headache, upper respiratory tract infection, and diarrhea.
