Supplementary Figure S10 from Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer

Identifying intratumor clonal selection and associated resistance mechanisms. a, Inferred tumor clones paired pre-treatment and post-cycle 2 CAPOX + trastuzumab scRNA-seq demonstrates rapid clearance of highly ERBB2 expression (red) clones, while many lower expressing clones persisted and even expanded. Contraction at the on-treatment timepoint reflects their RECIST response at their initial follow up imaging timepoint, demonstrating that patient 3, who had the highest ERBB2 expression, had the deepest and most durable response. b, Pre- and on-treatment size and fold-change of clones identified in pane a ordered by pre-treatment ERBB2 expression. Clonal expansion was most commonly seen in clones with low ERBB2 expression and was associated with a resistance program derived by GeneVector. c, MT1H, MT1E, MT2A, and MSMB expression were significantly higher in clones expanding despite CAPOX + trastuzumab (TC) versus both contracting clones after TC as well as expanding clones after CAPOX (C) only, suggesting association with therapeutic resistance. d, The resistance program strongly correlated with the CAPOX+trastuzumab clones, and poorly with CAPOX-treated clones, as intended.