Abstract
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
Cancer research (Chicago, Ill.), Vol.86(8_Supplement), pp.CT144-CT144
04/17/2026
DOI: 10.1158/1538-7445.AM2026-CT144
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.
Details
- Title: Subtitle
- 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
- Creators
- Anwaar Saeed - University of Pittsburgh Medical CenterHarshabad Singh - Global Cancer InstituteAlexander I. Spira - Inova Fairfax HospitalJason T. Henry - HealthONEDani Castillo - City Of Hope National Medical CenterNataliya Uboha - University of Wisconsin Carbone Cancer CenterNaomi Fei - University of IowaNicholas DeVito - Duke Medical CenterDiana Hanna - USC Norris Comprehensive Cancer CenterMichael J. Chisamore - Merck Institute for Science EducationGrace H. McGregor - Therapeutics Clinical ResearchHui Zou - Therapeutics Clinical ResearchMinghan Wang - Therapeutics Clinical ResearchSatya (Nanu) Das - Therapeutics Clinical ResearchRita Laeufle - Therapeutics Clinical ResearchMichael J. Overman - The University of Texas MD Anderson Cancer Center
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.86(8_Supplement), pp.CT144-CT144
- DOI
- 10.1158/1538-7445.AM2026-CT144
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- AMER ASSOC CANCER RESEARCH
- Language
- English
- Date published
- 04/17/2026
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9985157515102771
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