Phase Ib/II Study of Immunotherapy

The primary endpoint of the Phase Ib study was dose-limiting toxicity (DLT), with the intention that a Phase II study would be conducted if DLT occurred in fewer than two-sixths of the treated patients, whereas the study would be terminated if DLT occurred in two or more patients. DLT was defined as any of the following adverse events occurring within 21 d of initial drug administration: Grade 4 neutropenia > 7 d; ≥ Grade 3 neutropenia with fever (T ≥ 38.5 °C) lasting > 24 h; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding; Grade 4 anemia; ≥ Grade 3 clinically significant nonhematologic toxicity; ≥ Grade 2 immune-related cardiotoxicity, immune-related pneumonia, immune-related ophthalmopathy; and ≥ Grade 3 other immune-related toxicity.
The primary endpoint of the Phase II study was the major pathological response (MPR) rate, with secondary endpoints consisting of the R0 resection rate, pCR rate, safety, disease-free survival (DFS), event-free survival (EFS), and OS. The Becker standard was used to evaluate pathological regression of the primary tumor after surgery. No residual tumor cells were defined as type 1a, less than 10% were defined as type 1b, 10–50% were defined as type 2, and the remainder were defined as type 3. Pathological remission assessed at Grades 1a and 1b was considered to be MPR (including pCR), while pCR was defined as the absence of residual tumor cells (including primary tumors and lymph nodes).