The U.S. Food and Drug Administration granted breakthrough therapy designation to Pfizer’s Xalkori (crizotinib) for the treatment of a subgroup of difficult-to-treat systemic anaplastic large cell lymphoma (ALCL).
The FDA’s breakthrough therapy designation aims to expedite the development and review of a potential medication for the treatment of serious diseases. The drug developer must provide preliminary evidence indicating the therapy represents a substantial improvement over existing treatments.
ALCL is a rare type of non-Hodgkin’s lymphoma but one of the most common subtypes of T-cell lymphoma. Specifically, the designation covers cases of relapsed or refractory ALCL positive for the ALK protein, which typically affects children and young adults. Though both ALK-positive and negative ALCLs are treated as aggressive lymphomas, many patients still relapse or require alternative treatments.
Xalkori is a receptor tyrosine kinase inhibitor. It can block signal transmission from multiple proteins, including ALK and MET, stopping these proteins from working. As a result, researchers believe the therapy will reduce or stop the growth of ALCL cancer cells and cause their death.
The FDA’s decision was based on results from the two clinical trials — ADVL0912 (NCT00939770) and A8081013 (NCT01121588) — which showed significant antitumor activity in pediatric and adult patients treated with Xalkori.
ADVL0912 is a Phase 1/2 study assessing the maximum safe and tolerable dose of Xalkori, and evaluating preliminary clinical activity in children with relapsed or refractory solid tumors and ALCL. In turn, the A8081013 Phase 1 study evaluated Xalkori in children and adults with advanced, ALK-positive tumors other than NSCLC, including patients with relapsed or refractory ALCL.
Besides ALCL, Xalkori was also granted breakthrough therapy status for the treatment of patients with metastatic non-small cell lung cancer (NSCLC), which accounts for approximately 75 percent of lung cancer cases.
Specifically, the FDA’s decision on NSCLC covers patients with alterations in exon 14 of the MET gene, who show disease worsening on or after chemotherapy. Exons are the bits of DNA that contain the information for making proteins.
In the case of NSCLC, the FDA’s designation was based on Xalkori’s antitumor activity in a Phase 1 clinical trial (NCT00585195), which is currently enrolling participants.
“Biomarker-driven therapies have changed the way we treat cancer, helping to ensure that patients receive the right medicine for their disease,” Mace Rothenberg, MD, chief development officer, Oncology, for Pfizer Global Product Development, said in a press release.
“These breakthrough therapy designations for Xalkori exemplify our commitment to precision medicine development and delivering medicines that have the potential to transform the lives of patients whose cancers carry these genomic alterations,” Rothenberg added.
Xalkori is currently approved in the U.S. to treat patients with metastatic NSCLC whose tumors are ALK-positive or ROS1-positive. Xalkori is the only FDA-approved therapy indicated for these NSCLC subtypes.
