Pfizer has presented Phase II data showing that its next-generation tyrosine kinase inhibitor lorlatinib exhibited “clinically meaningful activity” against lung tumours and brain metastases.

Strong, durable responses were observed in patients with ALK-positive and ROS1-positive advanced non-small cell lung cancer (NSCLC), including those who were heavily pretreated, the firm noted.

According to the data, presented at the International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan, the overall response rate (ORR) was 90 percent in ALK-positive treatment-naïve patients, while the intracranial ORR (IC-ORR) was 75 percent.

For ALK-positive patients previously treated with Xalkori (crizotinib) with or without chemotherapy, the ORR was 69 percent and the IC-ORR 68 percent.

In ALK-positive patients previously treated with a non-crizotinib ALK inhibitor with or without chemotherapy, the ORR was 33 percent, while for ROS1-positive patients regardless of prior treatment, the response rate was 36 percent.

On the safety side, side effects were generally manageable and primarily mild to moderate in severity, the firm noted.

“The findings presented today suggest that lorlatinib, if approved, may represent an effective treatment option for patients with ALK-positive advanced non-small cell lung cancer across multiple lines of therapy,” said Professor Benjamin Solomon, lead investigator and medical oncologist at Peter MacCallum Cancer Centre, Melbourne, Australia.

“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.”

He also noted that controlling brain metastases “is very important to these patients and an especially challenging aspect of treating this disease, and that  “excellent intracranial responses” were observed across all patient groups, including those who were heavily pretreated.

Pfizer said the data will form the basis of discussions with global regulatory authorities, with a view to submitting lorlatinib - which already has a breakthrough status in the US - for the treatment of patients with ALK-positive metastatic NSCLC previously treated with one or more ALK inhibitors.