FDA Grants Priority Review to sNDA for Crizotinib to Treat Pediatric ALK+ ALCL

September 23, 2020

The supplemental new drug application seeks approval for crizotinib (Xalkori) to treat pediatric patients with relapsed or refractory systemic anaplastic large cell lymphoma that is ALK positive.

The FDA has accepted and granted priority review to the supplemental new drug application (sNDA) for crizotinib (Xalkori) for the treatment of pediatric patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) that is ALK positive, according to Pfizer, the developer of the tyrosine kinase inhibitor (TKI).

If approved, crizotinib would be the first biomarker-driven therapy for this type of pediatric lymphoma. The FDA has set a prescription drug user fee act (PDUFA) date for January 2021.

“Despite high survival rates for children with ALK-positive anaplastic large cell lymphoma, many will relapse, requiring novel treatment approaches,” Chris Boshoff, MD, PhD, chief development officer of Oncology at Pfizer Global Product Development, said in a press release. “Today’s FDA filing exemplifies Pfizer’s commitment to broadening the use of biomarker-driven therapies in areas with significant needs, such as rare, pediatric cancers. Given [crizotinib’s] proven efficacy in ALK-positive lung cancer and activity seen in clinical trials investigating relapsed or refractory ALK- and ROS1-positive anaplastic large cell lymphoma, if approved, [crizotinib] could represent an important step toward improving outcomes for children with this type of cancer.”

The sNDA is supported by results from the ADVL0912 (NCT00939770) and A8081013 (NCT01121588) studies.

ADVL0912 is a phase 1/2 study conducted in collaboration with the Children’s Oncology Group (COG) which is determining the maximum dose that is safe and tolerable and evaluating clinical activity in pediatric patients with relapsed or refractory solid tumors and ALCL. Study A8081013 is a phase 1 study evaluating crizotinib in pediatric and adult patients with advanced malignancies known to be ALK-positive other than non-small cell lung cancer (NSCLC) and included patients with relapsed or refractory ALCL.

According to Pfizer, both of these studies demonstrated compelling antitumor activity in pediatric and adult patients who received crizotinib.

“Children with cancer and their families have been desperate for new and innovative medicines. We applaud Pfizer’s commitment to drug discovery and development to help address childhood cancers and continue to work together on behalf of patients with these cancers,” George Dahlman, chief executive officer of Children’s Cancer Cause, said in the release. “We look forward to potentially having a new biomarker-driven therapy for children with relapsed or refractory ALK-positive ALCL that may help improve these children’s lives.”

Notably, the submission of the sNDA to the FDA is in addition to the European Medicines Agency’s agreement on a Pediatric Investigational Plan (PIP) for crizotinib, including the treatment of pediatric patients with relapsed or refractory systemic ALK-positive ALCL. Crizotinib also received breakthrough therapy designation (BTD) from the FDA for the ALK-positive ALCL indication in May 2018.

Crizotinib is currently indicated for the treatment of patients with metastatic NSCLC whose tumors are ALK-positive or ROS1-positive as detected by an FDA-approved test. The agent has received approval for patients with ALK-positive NSCLC in more than 90 countries worldwide including Australia, Canada, China, Japan, South Korea, and the EU. Crizotinib is also approved for the treatment of ROS1-positive NSCLC in more than 70 countries.

Reference:

FDA ACCEPTS SUPPLEMENTAL NEW DRUG APPLICATION FOR PFIZER’S XALKORI® (CRIZOTINIB) FOR THE TREATMENT OF PEDIATRIC ALK-POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA [news release]. New York. Published September 23, 2020. Accessed September 23, 2020. https://investors.pfizer.com/investor-news/press-release-details/2020/FDA-Accepts-Supplemental-New-Drug-Application-for-Pfizers-XALKORI-crizotinib-for-the-Treatment-of-Pediatric-ALK-positive-Anaplastic-Large-Cell-Lymphoma/default.aspx