Abstract CT144: Pharmacokinetics of spevatamig (PT886), a bispecific antibody targeting CLDN18.2 and CD47, in patients with advanced gastrointestinal cancers as monotherapy or combination therapy

Abstract Spevatamig (PT886) is an IgG1-based bispecific antibody targeting tumor cells expressing claudin 18.2 (CLDN18.2) and/or CD47 to mediate enhanced anti-tumor activity through innate immune cell and potentially T cell activation. Here we present the pharmacokinetic (PK) characteristics of spevatamig as monotherapy or combination therapy in patients with advanced gastrointestinal (GI) cancers. A total of 61 patients were included in this PK study: 31 patients with advanced GI cancers in spevatamig monotherapy dose escalation (0.1 mg/kg QW to 9 mg/kg Q2W) in a phase 1 trial, and 30 patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with spevatamig in combination with gemcitabine plus nab-paclitaxel (GnP) in a phase 2 trial, where 2 mg/kg once-weekly (QW), 3 mg/kg QW and other exploratory regimens were tested. Using data from these 61 patients, a 2-compartment population PK model with nonlinear (Michaelis-Menten) clearance was developed to describe spevatamig PK characteristics. Model-based PK simulation and non-compartmental analysis (NCA) were next performed at 2 mg/kg QW and 3 mg/kg QW in both monotherapy and GnP combinations. The results showed that GnP did not influence spevatamig exposure, evident by comparable AUCs. Simulated PK exposure revealed a notable accumulation following 5 repeated cycles at 2 mg/kg QW or 3 mg/kg QW in both spevatamig monotherapy and spevatamig + GnP combinations. Further, a statistically significant difference was observed between the estimated AUC0-168 of 2 mg/kg QW spevatamig + GnP and that of 3 mg/kg QW spevatamig + GnP (p = 5.4e-10, two sample T-test), indicating that 2 mg/kg QW and 3 mg/kg QW spevatamig are two independent dose levels suitable for clinical evaluation. In conclusion, model-based simulations indicate that spevatamig exhibits dose-dependent, increase in exposures either in monotherapy or combinations at two statistically distinct potentially efficacious dose levels. Combinations with GnP did not alter spevatamig exposure at 2 mg/kg QW or 3 mg/kg QW; overall, spevatamig exhibited PK characteristics suitable for combinatorial clinical development. Citation Format: Anwaar Saeed, Harshabad Singh, Alexander I. Spira, Jason T. Henry, Dani Castillo, Nataliya Uboha, Naomi Fei, Nicholas DeVito, Diana Hanna, Michael J. Chisamore, Grace H. McGregor, Hui Zou, Minghan Wang, Satya (Nanu) Das, Rita Laeufle, Michael J. Overman. Pharmacokinetics of spevatamig (PT886), a bispecific antibody targeting CLDN18.2 and CD47, in patients with advanced gastrointestinal cancers as monotherapy or combination therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT144.