Population Pharmacokinetics and Exposure-Response of Sasanlimab, a Checkpoint Inhibitor, in Patients with Non-Muscle Invasive Bladder Cancer and Other Solid Tumors.

Sasanlimab is a monoclonal antibody (mAb) which blocks human programed cell death protein 1. It is administered subcutaneously (SC), currently under development for non-muscle invasive bladder cancer (NMIBC) with a recommended flat dose of 300 mg every 4 weeks (Q4W). The objectives of the analyses were to characterize the population pharmacokinetics (popPK) of sasanlimab and to determine the exposure-response (ER) relationship between sasanlimab and safety endpoints of interest pooling data across clinical studies including various tumor types. Analyses for efficacy aimed to determine additional ER relationships within the NMIBC population. Sasanlimab PK was typical of IgG4 mAbs and was well characterized by a two-compartment model, with a small volume of distribution (central volume of 3.67 L, peripheral volume of 2.19 L), low systemic clearance (0.142 L/day), and elimination half-life of ∼29 days. Bioavailability from SC dosing was ∼70%. There was no evidence of time-dependent change in sasanlimab clearance, and no meaningful impact of body weight on exposure. There was no association found between sasanlimab exposure and any safety endpoint of interest: treatment-emergent adverse events of Grade ≥2 and Grade ≥3, and immune-related adverse events of Any Grade and Grade ≥3. For efficacy, no association was found between exposure and the key endpoints: investigator-assessed event free survival and complete response (in participants with carcinoma in situ). In total, the popPK results and absence of ER associations for safety and efficacy endpoints support the recommended flat dose of sasanlimab 300 mg SC Q4W.