Fig. 1. Circulating plasma ALK VAF varies with clinical response to therapy.

a In Group 1, circulating ALK VAF correlated with disease response, as patients’ tumors remained dependent on mutated activated ALK. In patients 1, 2, 5, 6, 13, 14, 17, 24, 25, 30, 31, 40, and 43, ALK VAF decreased with clinical response to lorlatinib and subsequently increased with disease progression. In patients 16, 26, 28, and 32, ALK VAF remained elevated as patients had progressive disease despite treatment. In patients 36, 41, 45, and 49 ALK VAF decreased with ongoing response to lorlatinib therapy. b In Group 2, circulating ALK VAF did not correlate with tumor response, decreasing despite disease progression—suggesting potential emergence of alternative oncogenic drivers of tumor growth. c In Group 3, circulating ALK was never detectable, and patients demonstrated persistent response to therapy (with the exception of sample 3 in patient 39 where minimal ALK VAF was detected at 0.18%). d Patient 3 harbored a germline ALK R1275Q mutation that remained stable at the expected 50% VAF, with complete response to lorlatinib. Patient numbers are annotated with a ‘c’ if they were receiving combination lorlatinib/chemotherapy, and with a ‘+’ sign if they had received prior ALK inhibitor therapy. All VAF values are given as ‘SV percent reads’ in Source Data. VAF variant allele frequency, ctDNA circulating tumor DNA. Source data are provided as a Source Data file.