The problem: ALK resistance to targeted therapy
People with non-small cell lung cancer (NSCLC) who are receiving targeted therapy for a confirmed ALK mutation can often become resistant to these treatments. Their cancer may grow again or show up in more locations. This trial sought to understand why and identify new treatment options for people living with ALK-positive NSCLC.
The SPACEWALK trial
The SPACEWALK trail studied how ALK-positive lung cancer changes, starts growing again, and/or comes back after individuals receive treatment with targeted therapy for ALK-positive NSCLC.
Patients whose cancer started growing after receiving targeted therapy for ALK-positive NSCLC [Alecensa (alectinib), Alunbrig (brigatinib), Zykadia (ceritinib), or Lorbrena (lorlatinib)] had their blood drawn and sent for analysis of biomarker changes. The findings of this study helped to better understand ALK biology and helped inform treatment decisions.
What did we learn?
The SPACEWALK study has concluded. A publication of the study’s major findings can be found in the Journal of Thoracic Oncology, Clinical and Research Reports.
Of the 62 individuals enrolled in the study with ALK-positive NSCLC: 8 persons (30%) were found to have a second ALK mutation that led to resistance to the current ALK-targeted therapy; 3 persons (11%) were found to have secondary bypass mutations in another gene (most commonly MET) that led to resistance to the current ALK-targeted therapy; and 6 persons (22%) were found to have both resistance mechanisms leading to resistance to ALK-targeted therapy.
In addition, genotype testing of patient plasma for tumor DNA was determined to be an ideal means for determining resistance to ALK-targeted therapy, despite challenges in isolating enough tumor DNA in samples. The findings suggest plasma genotyping may be the best way of tracking emerging resistance to targeted therapy for persons with ALK-positive NSCLC.
GO2 for Lung Cancer’s involvement
The trial, performed through our medical institute ALCMI, is led by Dr. Mark Award of Dana Farber Cancer Institute. It was originally launched by Dr. Geoffrey Oxnard of DFCI, a prior chair of GO2 for Lung Cancer’s Scientific Leadership Board.