Strong, durable responses seen against lung tumors and brain metastases across multiple lines of therapy.
Mid-stage data shows that Pfizer’s lorlatinib could provide benefits to lung cancer patients who exhibit related brain tumors.
This morning, Pfizer announced that lorlatinib, a tyrosine kinase inhibitor, exhibited clinically meaningful activity against lung tumors and brain metastases in a range of patients with ALK-positive and ROS1-positive advanced non-small cell lung cancer (NSCLC), including those who were heavily pretreated.
Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier, which is why it’s showing efficacy in treating brain metastases. In April, the U.S. Food and Drug Administration granted Breakthrough Therapy designation for lorlatinib for the treatment of patients with ALK-positive metastatic NSCLC previously treated with one or more ALK inhibitors.
Benjamin Solomon, Pfizer’s lead investigator and medical oncologist at Peter MacCallum Cancer Centre in Melbourne, Australia, said the results suggest that lorlatinib could represent an “effective treatment” for patients diagnosed with ALK-positive advanced non-small cell lung cancer across multiple lines of therapy. Mid-stage data was derived from patients in six different cohorts based on biomarker (ALK-positive of ROS1-positive) and prior therapies. The primary endpoints were objective response rate (ORR) and intracranial ORR (IC-ORR) confirmed by independent central review (ICR).
“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. 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,” Solomon said in a statement.
The company said side effects were mild to moderate and “generally manageable.”
Mace Rothenberg, Pfizer’s chief oncology development officer, said it is important to understand the different mutations that can occur in lung cancer. In a statement, he pointed to Pfizer’s Xalkori (crizotinib), which was the first drug approved for patients with ALK-positive and ROS1-positive NSCLC.
“By understanding the mutations that occurred in patients that rendered their tumors resistant to Xalkori and other ALK inhibitors, medicinal chemists working at Pfizer were able to design a molecule with the potential to overcome that resistance and inhibit ALK despite these mutations,” Rothenberg said.
Rothenberg added that the Phase II results demonstrate the first clinical evidence of the activity of lorlatinib at this setting. He said the experimental drug is an “extraordinary example” of what can be achieved through precision medicine development.
