Pfizer Inc. announced, on October 16, 2017, full results from the Phase 2 clinical trial of the investigational, next-generation tyrosine kinase inhibitor lorlatinib that 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.
Further, side effects were generally manageable and primarily mild to moderate in severity. The results were presented by Professor Benjamin Solomon, lead investigator and medical oncologist at Peter MacCallum Cancer Centre, Melbourne, Australia, during an oral session at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan. Pfizer will also present data from several other lung cancer clinical programs.
“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. 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,” Professor Solomon said. “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 an extraordinary example of what can be achieved through translational research and precision medicine development. Recall that Xalkori (crizotinib) 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. We are very encouraged by the results of this Phase 2 trial that provide the first clinical evidence of the activity of lorlatinib in this setting,” said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development.
The Phase 2 study examined the antitumor activity and safety of lorlatinib in 275 patients with or without asymptomatic, untreated or treated brain metastases.
Lorlatinib was generally tolerable. Most adverse events were mild to moderate and were managed by dose reductions or delay or with standard medical therapy. There were no treatment-related deaths and a low (3%) rate of discontinuation due to drug-related adverse events.
The Phase 2 data will form the basis of discussions with global regulatory authorities, including the U.S. Food and Drug Administration. On April 26, 2017, the FDA granted Breakthrough Therapy designation for lorlatinib for the treatment of patients with ALK-positive metastatic NSCLC previously treated with one or more ALK inhibitors.
About Non-Small Cell Lung Cancer
Lung cancer is the leading cause of cancer death worldwide. NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting. Approximately 75 percent of NSCLC patients are diagnosed late with metastatic or advanced disease where the five-year survival rate is only five percent.
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