Abstract CT112: Clinical validation of a first-in-class pan-cancer antibody Vartumab targeting oncofetal chondroitin sulfate

Abstract The development of novel antibody-based cancer therapies is challenged by the scarcity of actionable tumor targets. Human tumors make and display a conserved oncofetal chondroitin sulfate (CS) glycosaminoglycan as a modification to proteins found on the surface of tumor cells, cancer-associated fibroblasts, and as structural components of the tumor microenvironment. In non-pathological conditions, oncofetal CS is found exclusively in fetal tissues with absent/minimal presentation in normal tissues after birth. We have identified a monoclonal antibody (Vartumab C9) with specificity to oncofetal CS in diverse malignancies, such as melanoma, sarcoma, AML, pancreatic cancer, as well as lung, colorectal, breast, and gastric cancers. Biodistribution studies in animals confirmed specific Vartumab C9 tumor accumulation upon intravenous administration. Vartumab C9-derived ADCs are well tolerated in rodents and show profound antitumor activity across a wide range of animal models. To qualify oncofetal CS as a novel pan-cancer target in humans, we have initiated a phase 0 micro-dosing PET imaging trial (VARTUTRACE) in all-commers (n=32) with solid tumors (NCT06645808). Non-stratified patients with solid tumors received a single micro-dose IV of a Zr89-Vartumab C9 (VTP-01, 1mg, 15 MBq) and whole-body images were obtained with PET/CT at days 1, 2, and 4. All injections were well tolerated and no adverse events reported. At time of submission, five cancer patients (lung cancer (n=2), esophagus cancer (n=2), and rectal cancer (n=1) patients) were dosed with VTP-01. Clear tumor accumulation was observed in all patients by day 4, with limited off-target binding. Post-imaging lesion biopsies confirmed target presence. No product-related adverse reactions were observed to date.Collectively, these findings support Vartumab C9 as a promising clinical validated first-in-class, tumor targeting antibody with broad potential to deliver therapeutics across diverse malignancies. GMP production for a phase I-IIa Vartumab C9-derived ADC trial is ongoing. Citation Format: Mads Daugaard, Tobias Gustavsson, Elena E. Vidal-Calvo, Swati Choudhary, Robert Dagil, Anne-Fleur S. Verhaar, Noortje C. van Dijk, Hendrikus H. Boersma, Andor W.J.M. Glaudemans, Danielle J. Vugts, Daniël Waagmeester, Yester Janssen, Maarten Brom, Frederico M. Pimenta, Gooitzen M. van Dam, Ali Salanti. Clinical validation of a first-in-class pan-cancer antibody Vartumab targeting oncofetal chondroitin sulfate [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 CT112.