Dive Brief:
- According to Phase 2 data presented at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan, Pfizer's ALK-inhibitor lorlatinib showed clinically meaningful activity against lung tumors and brain metastases in patients with ALK-positive and ROS1-positive advanced non-small cell lung cancer (NSCLC). This included heavily pretreated patients.
- Overall response rates (ORR) and intracranial response rates (IC-ORR) were highest in ALK-positive treatment-naïve patients at 90% and 75%, respectively. Patients previously treated with one or more ALK inhibitors had ORRs of 33-69% and IC-ORRs of 42-68%.
- Now in Phase 3, lorlatinib has breakthrough therapy designation for ALK-positive metastatic non-small cell lung cancer already treated with one or more ALK inhibitors. Pfizer is sufficiently confident of its Phase 2 data to use it as a basis for discussions with the Food and Drug Administration and other global regulatory authorities.
Dive Insight:
"These are comprehensive data in non-small cell lung cancer patients previously treated with second-generation ALK inhibitors who currently have few available treatment options," said Professor Benjamin Solomon, lead investigator and medical oncologist at Peter MacCallum Cancer Centre, Melbourne, Australia. "Controlling brain metastases is very important to these patients and an especially challenging aspect of treating this disease. We saw excellent intracranial responses in all patient groups, including those who were heavily pretreated."
Lorlatinib is a follow up to Pfizer's Xalkori (crizotinib), a standard of care in NSCLC. The ongoing CROWN study is an open-label two arm study comparing lorlatinib with Xalkori in first-line treatment of patients with metastatic ALK-positive NSCLC.
Xalkori has faced a struggle of late, with three competitors in ALK-positive lung cancer used for patients who don't respond or can't take Pfizer's drug, and lorlatinib could be the boost that the franchise is looking for.
Xalkori has been bested by Roche's Alecensa (alectinib) in a Phase 3 head-to-head study in ALK-positive non-small cell lung cancer, including prevention of brain metastases. Alecensa has accelerated approval for NSCLC patients who previously failed on Xalkori. Novartis' Zykadia (ceritinib) has received approval for both first- and second-line treatment of NSCLC, and most recently, Takeda's Alunbrig (brigatinib) has snagged second-line approval and is aiming for first line with a Phase 3 trial head-to-head with Xalkori.