	US 12,071,661 B2
	Method of predicting response to therapy by assessing tumor genetic heterogeneity
Fergal Casey, Pleasanton, CA (US); John J. Lee, Walnut Creek, CA (US); John F. Palma, Alamo, CA (US); and Stephanie J. Yaung, San Jose, CA (US)
Assigned to Roche Sequencing Solutions, Inc., Pleasanton, CA (US)
Appl. No. 16/968,811
Filed by Roche Sequencing Solutions, Inc., Pleasanton, CA (US)
PCT Filed Feb. 11, 2019, PCT No. PCT/EP2019/053272 § 371(c)(1), (2) Date Aug. 10, 2020, PCT Pub. No. WO2019/155050, PCT Pub. Date Aug. 15, 2019.
Claims priority of provisional application 62/629,635, filed on Feb. 12, 2018.
Prior Publication US 2021/0002719 A1, Jan. 7, 2021
Int. Cl. C12Q 1/6869 (2018.01); A61K 31/4745 (2006.01); G16H 50/30 (2018.01)

CPC C12Q 1/6869 (2013.01) [A61K 31/4745 (2013.01); G16H 50/30 (2018.01); C12Q 2600/158 (2013.01)]

5 Claims

1. A method for identifying a cancer patient as likely to positively respond to a therapy regimen, the method comprising the steps of:

(a) providing samples obtained from the patient comprising at least one solid tumor sample and at least one blood plasma sample;

(b) determining in the samples the sequence of at least a portion of each of the biomarkers APC, KRAS, ABL1, FGFR3, JAK3, RAF1, BRCA1, MET, AKT1, FLT1, KDR, RNF43, BRCA2, TP53, AKT2, FLT3, MAP2K1, TERT promoter, EGFR, KIT, ARAF, FLT4, MAP2K2, TSC1, ERBB2, NRAS, CDK6, GATA3, MTOR, TSC2, ALK, PDGFRA, CSF1R, GNA11, NFE2L2, PTEN, BRAF, RET, CTNNB1, GNAQ, NTRK1, RB1, DPYD, ROS1, DDR2, GNAS, PDGFRB, SMAD4, AR, MSH2, EZH2, IDH1, PIK3CA, SMO, CCND1, MSH6, FGFR1, IDH2, PIK3R1, STK11, CCND2, NF2, FGFR2, JAK2, PTCH1, VHL, CCND3, PDCD1LG2, CDK4, ESR1, KEAP1, UGT1A1, CD274, PMS2, CDKN2A, FBXW7, and MLH1;

(c) determining a measure of tissue-plasma genetic heterogeneity in the biomarker sequence, the measure of genetic heterogeneity selected from plasma recovery rate (PRR) and multi-variant gene count (MVGC);

(d) identifying the patient as likely to positively respond to a less aggressive therapy regimen if the measure of genetic heterogeneity is low and administering the less aggressive therapy regimen; or

(e) identifying the patient as not likely to positively respond to a less aggressive therapy regimen if the measure of genetic heterogeneity is high and administering a more aggressive therapy regimen,

wherein the measure of genetic heterogeneity is low for PRR<0.8 or MVGC=0, and wherein the measure of genetic heterogeneity is high for PRR≥0.8 or MVGC>0,

wherein the cancer is selected from among non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) in stages I, II, III and IV,

wherein the positive response to therapy is selected from increased progression free survival (PFS) and increased overall survival (OS),

wherein, the more aggressive therapy regimen comprises at least one of a higher dose of therapy, addition of one or more therapeutic agents, and extended duration of therapy as compared to the less aggressive therapy regimen.