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-programmed cell death protein-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 2 of the first 3 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 4 to 6 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% (thigh) and 72.4% (abdomen). In Part 2 (N = 22), subcutaneous tislelizumab in the thigh showed consistent pharmacokinetics with Part 1. Preliminary analysis showed overall response rate of 44.4%; 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.