GPA33-SADA / SERB Pharmaceuticals, Memorial Sloan-Kettering Cancer Center, Massachusetts Institute of Technology - LARVOL DELTA

Pre-targeted radioimmunotherapy using self-assembling dis-assembling (SADA) bispecific antibodies for the treatment of appendiceal carcinoma [WITHDRAWN] (AACR 2025) - "SADA-PRIT exploits an initial long plasma half-life of SADA tetramers for increased tumor uptake and when unbound, their disassembly to monomer with rapid renal clearance, thereby maximizing therapeutic indices across all critical normal tissues.2,3 6-week old female BRG mice with subcutaneous (sq) or intraperitoneal (IP) patient derived AC xenograft (PDX) were treated with two doses of α-PRIT using [225Ac]-Proteus ([225Ac]Pr, or three doses of β- PRIT using [177Lu]DOTA,4 all delivered by anti-GPA33-SADA...Minimal myeloid, renal, hepatic, or neural toxicities were seen. IHC results support future testing of cocktailing of SADAs (specific for GPA33, B7H3, and HER2) to overcome tumor heterogeneity while reducing on-target off-tumor side effects."

Appendix Cancer • Oncology • Solid Tumor • CD276 • HER-2

Dose escalation and curative therapy of colorectal cancer with anti-GPA33 Self-Assembling and Disassembling (SADA) Actinium-225 Alpha Pretargeted Radioimmunotherapy (SNMMI 2024) - "0001) for antibody only, [225Ac]Pr only, and irrelevant (GD2-SADA) control groups, and GPA33-SADA groups receiving 37kBq, 74kBq, 37+37kBq, 37+74kBq respectively; for the 74kBq+74kBq (1. We conclude that α-SADA-PRIT using 225Ac induced major tumor response and significantly prolonged survival with minimal myelo, renal, hepatic, or neural toxicities. MTD has not been reached."

CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Leukopenia • Lung Cancer • Neuroblastoma • Oncology • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor

Anti-GPA33 Pretargeted Radioimmunotherapy (PRIT) of Colorectal Cancer (CRC) Using a Self-Assembling and Dis-Assembling (SADA) Bispecific Antibody to deliver 177Lu-Bivalent Benzyl-DOTA (SNMMI 2024) - P1 | "These studies showed that bivalent [177Lu]Lu-Gemini improved tumor uptake and tumor retention without comprising TIs when used in GPA33-SADA PRIT. The first-in-human [177Lu]Lu-DOTA SADA-PRIT phase 1 clinical trial (targeting GD2) (NCT05130255) has confirmed safety of the SADA system. The clinical translation of bivalent versus monovalent ligands for SADA-PRIT, especially when applied to GPA33(+) CRC seems prudent."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor