(a) We investigated co-occurrence of mutations in DNA damage repair genes involved in base excision repair (DDR-BER), DNA damage sensoring (DS), the Fanconi anemia pathway (FA), homologous recombination (DDR-HR), mismatch repair (DDR-MMR), nucleotide excision repair (DDR-NER), non-homologous end joining (DDR-NHEJ) and translesion DNA synthesis (DDR-TLS). Mutations were characterized by consequence (missense, frameshift, nonsense, splice site, in-frame) and recurrence (hotspots) and loss of the wild type allele was considered in case of truncating mutations (biallellic inactivation). A similar analysis was performed for genes involved in the WNT pathway. A high TMB tumor with biallellic inactivation of MLH1 and a tumor with a gain-of-function beta-catenin hotspot mutation were identified among responders (N=41 patients) and non-responders (N=46 patients) respectively, with no additional significant differences in genomic alterations in the DDR and WNT pathways between responders and non-responders. We defined response as durable clinical benefit (DCB) if complete, partial response or stable disease was achieved with a duration >6months. (b) The number of mutations with at least one fit MANA (determined as neopeptides with a predicted MHC affinity < 50nM for which the wild type peptides has a predicted MHC affinity of > 1000nM) in each tumor, divided by clonality and hotspot status is shown in the top distribution graph. Clinical response and overall survival are shown in the middle panel. Clonal hotspot frameshifts and in-frame insertions and deletions in ANTRX2, TP53, EGFR, ASXL1, NOTCH2, ZFP36L2, FAM171B, SLC35F5, CD93 and SLAMF1 generated fit MANAs shown in the lower panel. There was no difference in the fraction of clonal fit MANAs between responding (N= 33 tumors) and non-responding (N=41 tumors, Mann Whitney U test p=0.65) tumors. We defined response as durable clinical benefit (DCB) if complete, partial response or stable disease was achieved with a duration >6months. NDB: No durable benefit.