Pharmacokinetics, pharmacodynamics and immunogenicity assessments
BLOOD
For PK studies, blood samples were collected at the following time points during single-dose phase (cycle 1): −0.5 h (pre-dose), 5 min (min), 2 h, 6 h, 24 h, 48 h, day 8 (D8), D15, and D22 after end of infusion. After entering multiple-dose phase, for Q2W cohort, blood samples were collected on D1 and D15 at 0.5 h prior to infusion and within 5 min after end of infusion each treatment cycle from cycle 2 (except for cycle 5). In cycle 5, blood samples were collected at −0.5 h (pre-dose), 5 min, 2 h, 6 h, 24 h, 48 h, and D8. For the Q3W cohorts, blood samples were collected on D1 at 0.5 h prior to infusion and within 5 min after end of infusion each treatment cycle from cycle 2 (except for cycle 6). In cycle 6, blood samples were collected at −0.5 h (pre-dose), 5 min, 2 h, 6 h, 24 h, 48 h, D8, and D15 after end of infusion. The single-dose plasma PK parameters included area under the concentration–time curve (AUC), maximum observed plasma concentration (CFor PD-1 receptor occupancy (RO), QL1604 binding to PD-1 molecules was detected by flow cytometry. Blood samples were collected at the at the following time points during single-dose phase (cycle 1): −0.5 h (pre-dose), 5 min, D2, D3, D8, D15, and D22 (for patients in the Q3W dose group, blood samples were not collected on D22) after end of infusion. After entering multiple-dose phase, for Q2W cohort, blood samples were collected on D1 and D15 at 0.5 h prior to infusion each treatment cycle from cycle 2 (except for cycle 5). Blood samples were collected at −0.5 h (pre-dose), 5 min, D2, D3, D8, D15, and D22 after end of infusion in cycle 5. For Q3W cohorts, blood samples were collected on D1 at 0.5 h prior to infusion each treatment cycle from cycle 2 (except for cycle 6). Blood samples were collected at −0.5 h (pre-dose), 5 min, D2, D3, D8, and D15 after end of infusion in cycle 6.The formation of antidrug antibodies (ADA) was analyzed for determining immunogenicity. Blood samples for immunogenicity were collected at −0.5 h (pre-dose), D8, D15, and D22 after end of infusion in during single-dose phase (cycle 1) (for patients in the Q3W dose group, blood samples were not collected on D22). After entering multiple-dose phase, for Q2W cohort, blood samples were collected on D1 and D15 at 0.5h prior to infusion each treatment cycle from cycle 2 (except for cycle 5). Blood samples were collected at −0.5 h (pre-dose), D8, D15, and D22 after end of infusion in cycle 5. For Q3W cohorts, blood samples were collected on D1 at 0.5 h prior to infusion each treatment cycle from cycle 2 (except for cycle 6). Blood samples were collected at −0.5 h (pre-dose), D8, and D15 after end of infusion in cycle 6.