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WCLC 2025 | Insights into novel treatment strategies for early-stage ALK-positive NSCLC

Jay Lee, MD, University of California, Los Angeles, CA, comments on the future of early-stage ALK-positive non-small cell lung cancer (NSCLC). Whilst alectinib is the only ALK TKI approved in this setting, multiple first, second, and third generation ALK inhibitors are approved in the metastatic setting. This underscores the need for further research and development in the early stage setting, with notable trials such as the NAUTIKA1 (NCT04302025) and ALNEO (NCT05015010) trials providing valuable insights into the standard of care for ALK-positive patients. This interview took place at 2025 World Conference on Lung Cancer (WCLC) in Barcelona, Spain.

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Transcript

So in the early stage setting, the only targeted therapy that’s out directed approved by the FDA in the United States is alectinib. There are no other out directed TKIs that are approved. This is very different from the metastatic setting where you have first, second, and third generation ALKIs that are approved in the first line setting. The fourth generation NVL-655 has not been approved in the metastatic setting...

So in the early stage setting, the only targeted therapy that’s out directed approved by the FDA in the United States is alectinib. There are no other out directed TKIs that are approved. This is very different from the metastatic setting where you have first, second, and third generation ALKIs that are approved in the first line setting. The fourth generation NVL-655 has not been approved in the metastatic setting. So there’s much work to be done in the early stage setting. And we have the phase three ALEX trial that established alectinib in the adjuvant setting to be standard of care in ALK positive patients. NeoALTTO 1 and Neo-ALTTO are two phase two trials that looked at neoadjuvant plus adjuvant or perioperative approach and really favorable, clinically meaningful pathologic regression data as well as radiographic response data that really adds to our standard of care for ALK.

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