ADCE-T02 - A clinical stage antibody drug conjugate targeting tissue factor demonstrates strong efficacy in preclinical models of head and neck squamous cell carcinoma

Tissue Factor (TF, F3, coagulation factor III, thromboplastin, or CD142), a membrane protein involved in blood coagulation, demonstrates confined expression to the perivascular compartment in healthy tissues but is over-expressed in many solid tumors, making it an attractive target for Antibody Drug Conjugates (ADC). The TF-targeted ADC Tisotumab vedotin is approved for treatment of cervical cancer and has demonstrated efficacy in Head and Neck Squamous Cell Carcinoma (HNSCC) 1 , but treatment is limited by substantial side effects including ocular toxicities, peripheral neuropathy, and bleeding warranting development of a more efficacious and better tolerated modality. ADCE-T02 is a clinical stage TF-targeted ADC composed of a humanized anti-TF antibody specifically designed to limit the impact on blood coagulation, conjugated via a novel T1000 linker moiety to the Topoisomerase-1 inhibitor Exatecan payload at a drug-to-antibody ratio of ~4. The expression level of TF was evaluated in patients with HNSCC, confirming broad and high TF expression in the majority of tumors, regardless of Human Papilloma Virus (HPV) status. In vitro, the efficacy of ADCE-T02 was evaluated and confirmed in a panel of HNSCC tumor cell lines with varying TF expression levels. In vivo, ADCE-T02 also demonstrated strong anti-tumor activity in both cell line and patient derived HNSCC xenograft models with varying TF expressions. Intriguingly, strong efficacy of ADCE-T02 (dosed from 1 mg/kg) was observed in HNSCC tumors expressing high levels of Epidermal Growth Factor Receptor (EGFR) but with limited response to anti-EGFR therapy. Furthermore, administration of a single dose of ADCE-T02 to mice bearing large tumors (≥1000mm 3 ) caused remarkable tumor shrinkage often resulting in complete tumor eradication. In addition, strong antitumor responses of a single dose of ADCE-T02 were observed in large tumors growing out following anti-EGFR therapy. In summary, ADCE-T02 demonstrates broad efficacy in HNSCC models with varying levels of TF expression including models resistant to EGFR targeted agents. A phase I clinical study of ADCE-T02 in patients with advanced solid tumors is currently ongoing and actively recruiting (Clinical Trial ID NCT06597721). 1 Sun et al., J. Clin. Oncol.; 42 (16 suppl.); 2024