he FDA has granted a breakthrough therapy designation to lorlatinib for use in patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) who have previously received 1 or more ALK inhibitors, according to Pfizer, the company developing the next-generation ALK/ROS1 tyrosine kinase inhibitor (TKI).
“This regulatory designation recognizes the potential for lorlatinib to provide an important treatment option for patients with ALK-positive NSCLC whose cancers have progressed despite treatment,” Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development, said in a release. “Pfizer’s rapid development of lorlatinib reflects a commitment to developing biomarker-driven therapies to meet the evolving needs of patients.”
The FDA grants Breakthrough Therapy status to expedite the development and review of a potential new medicine that treats a serious or life-threatening disease, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies.
Many patients with ALK– or ROS1-positive NSCLC develop resistance to TKI therapy, with the central nervous system (CNS) as a common site of relapse. Lorlatinib is a selective brain-penetrant ALK/ROS1 TKI active against most known resistance mutations.
The company submitted results to the FDA from the ongoing phase I/II study NCT01970865 (N = 54) presented at the 17th World Conference on Lung Cancer in 2016. As of January 2016, the study had accrued 41 patients who were ALK-positive, 12 who were ROS1-positive, and the mutation status of 1 patient was not recorded at cutoff.
Twenty-seven patients had received at least 2 prior TKIs before joining the study, 20 had received 1 prior TKI, and 7 were TKI-naïve. At baseline, 39 patients had CNS metastases. Twenty-six patients remain on-trial.
Patients received lorlatinib on day –7, then daily at 10 dose levels from 10 mg to 200 mg.