Bispecific-antibody therapy (BAT), the next strategy of immunotherapy for tumor patients, has showed the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers were developed to monitor the response. Here, we investigated the first BAT longitudinal plasma proteome profiling including 86 longitudinal samples from 22 tumor patients who received anti-PD1 and anti-CTLA4 BAT therapy and 24 healthy control samples, which might be beneficial to explore the biomarker for BAT.