Subcutaneously Administered Tislelizumab in Locally Advanced or Metastatic Non-Small Cell Lung Cancer: Pharmacokinetics and Safety Results from the BGB-A317-103 Phase I Study

Purpose: Tislelizumab, an anti-PD-1 monoclonal antibody, is approved for various indications intravenously. Subcutaneous delivery offers potential advantages in convenience and resource utilization. BGB-A317-103 assessed pharmacokinetics, safety, and efficacy of subcutaneous tislelizumab in treatment-naïve patients with advanced or metastatic non-small cell lung cancer. Patients and methods: BGB-A317-103 is an open-label, multicenter, phase I study. In part 1 (dose/injection site exploration), patients received subcutaneous tislelizumab (abdomen or thigh injections; 300 mg) in two of the first three cycles and intravenous tislelizumab (200 mg) in the remaining cycle, followed by intravenous tislelizumab thereafter. In part 2 (dose expansion), patients received 300 mg of subcutaneous tislelizumab in the thigh in all cycles. Both parts included chemotherapy during the first four to six cycles. Pharmacokinetics, bioavailability, efficacy, immunogenicity, and safety were assessed. Results: At data cutoff (December 6, 2024), in part 1 (N = 39), subcutaneous administration yielded higher trough concentrations than intravenous [geometric means: 23.1 μg/mL (thigh), 19.5 μg/mL (abdomen), and 14.8 μg/mL (intravenously)]. Estimated bioavailability was 85.6% for thigh and 72.4% for abdomen. In part 2 (N = 22), subcutaneous tislelizumab in the thigh showed consistent pharmacokinetics with part 1. Preliminary analysis showed an overall response rate of 44.4%; the median duration of response and median progression-free survival were not reached. Tislelizumab's safety profile was consistent with previous studies, with no new signals or injection-site reactions. Conclusions: Subcutaneous tislelizumab demonstrated high bioavailability after thigh and abdomen injections. Safety and efficacy were consistent with previous tislelizumab plus chemotherapy studies, warranting further investigation of subcutaneous tislelizumab.