Table 7.

Translational work-up

• Tumor-infiltrating lymphocytes (TiL) repertoire determination from tumor

• Liquid biopsy next-generation sequencing (NGS) immunoprofiling (TCRβ & IgH) before treatment initiation and before second cycle to determine response predictive immune signature (diversification pattern as read-out for ongoing immune activation, TiL clone expansion in peripheral blood)

• In addition, FFPE will be centrally tested for PD-L1, HER2 (IHC and ISH), MSI, EBV and HER signaling alterations (amplifications and/or mutations in e.g. EGFR, HER2, HER3, PIK3CA) and correlated with clinical efficacy

• CTC will be evaluated for changes in HER2 and PD-L1 status

• ctDNA will be evaluated for HER signaling alterations (amplifications and/or mutations in e.g. EGFR, HER2, HER3, PIK3CA)

• Central imaging review and determination of ORR and PFS according to modified RECIST