U.S. flag An official website of the United States government
  1. Home
  2. Drugs
  3. Development & Approval Process | Drugs
  4. Drug Approvals and Databases
  5. Resources for Information | Approved Drugs
  6. Project Orbis: FDA approves acalabrutinib for CLL and SLL
  1. Resources for Information | Approved Drugs

Project Orbis: FDA approves acalabrutinib for CLL and SLL

On November 21, 2019, the Food and Drug Administration approved acalabrutinib (CALQUENCE, AstraZeneca) for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The FDA, the Australian Therapeutic Goods Administration, and Health Canada collaborated on this review.

Approval was based on two randomized, actively controlled trials in patients with CLL:  ELEVATE-TN (NCT02475681) and ASCEND (NCT02970318). Efficacy in both trials was based on progression-free survival (PFS) as assessed by independent review.

ELEVATE-TNrandomized 535 patients with previously untreated CLL to one of three arms: acalabrutinib monotherapy, acalabrutinib plus obinutuzumab, or obinutuzumab plus chlorambucil. With a median follow-up of 28.3 months, PFS was significantly improved in both acalabrutinib arms. Compared to the obinutuzumab plus chlorambucil arm, the hazard ratio (HR) for PFS was 0.10 (95% CI: 0.06, 0.17; p < 0.0001) with acalabrutinib plus obinutuzumab and 0.20 (95% CI: 0.13, 0.30; p < 0.0001) with single agent acalabrutinib.

ASCEND randomized 310 patients with relapsed or refractory CLL after at least one prior systemic therapy to receive either acalabrutinib or investigator’s choice (either idelalisib plus a rituximab product, or bendamustine plus a rituximab product). With a median follow-up of 16.1 months, PFS was significantly longer in the acalabrutinib arm compared to the investigator’s choice arm (HR 0.31; 95% CI, 0.20, 0.49; p < 0.0001).

In both trials, median PFS had not been reached in the acalabrutinib arms. In addition,  median overall survival had not been reached in any arm for either trial, with fewer than 15% of patients experiencing an event.

The most common adverse reactions (≥ 30%) of any grade in patients with CLL were anemia, neutropenia, thrombocytopenia, headache, upper respiratory tract infection, and diarrhea.

The recommended dose is 100 mg orally every 12 hours; swallow whole with water and with or without food.

View full prescribing information for CALQUENCE.

This review used the Real-Time Oncology Review (RTOR) and Assessment Aid pilot programs, which streamlined data submission prior to the filing of the entire clinical applications, and facilitated discussions among the regulatory agencies. These applications were approved four months prior to the FDA goal date. The FDA granted these applications Priority Review and Breakthrough Therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

Follow the Oncology Center of Excellence on Twitter @FDAOncology.