Table 2.

Study endpoints.

Primary endpoint
•To determine the pCR rate
Secondary endpoints
•Recurrence-free survival at 2 years, 3 years, and at the end of the study. Recurrence-free survival is defined as the time from randomization to recurrence event (local or distant disease development or death). •Overall survival is defined as the time from randomization to death. •Pathological overall response rate is defined as the sum of pCR, near pCRs and pathologic partial responses. •Safety: frequency of the following treatment-emergent AEs while on treatment or within 30 days after the last study treatment: All AEs, grade 3–5 AEs, serious AEs, AEs of special interest, and AEs leading to treatment discontinuation or withdrawal from the study. •To determine molecular and immunophenotypic changes in tumor and peripheral blood by evaluating several biomarkers. Since identifying new markers for immunotherapy is rapidly evolving, the definitive list of analyses remains to be determined. The following tests are suggested (differences: baseline, during the adjuvant treatment at week 6, surgical time points, and at recurrence will be compared): •Immunoscore (densities of tumor-infiltrating CD3 and CD8 cells), as well as PD-L1 expression on tumor and immune cells, evaluated by immunohistochemical analysis with an automated quantification system and a standardized assay on tumor tissue •Circulating cytokines and chemokines profiling, evaluated by Luminex technology in patient peripheral blood samples •Myeloid-derived suppressors cells and immune cell subtypes expression and lymphocyte activation, evaluated by multicolor cytofluorimetric approach in patient peripheral blood samples •Metabolomic profiling in patient peripheral blood samples, evaluated by nuclear magnetic resonance Spectrometer (600 MHz) •Tumor mutational burden by whole-exome sequencing on tumor and matched normal tissue at baseline. •Additional analysis of protein levels (i.e., CCR5), DNA mutations, and/or mRNA analysis to enable molecular classification (e.g., CMS), as well as other exploratory markers related to immunotherapy in tumor tissues

AE: Adverse event; pCR: Pathologic complete response.